BACKGROUND Colorectal cancer(CRC)is a prevalent malignant tumor involving adenomas that develop into malignant lesions.Carcinoembryonic antigen(CEA)is a non-specific serum biomarker upregulated in CRC.The concentratio...BACKGROUND Colorectal cancer(CRC)is a prevalent malignant tumor involving adenomas that develop into malignant lesions.Carcinoembryonic antigen(CEA)is a non-specific serum biomarker upregulated in CRC.The concentration of CEA is modulated by tumor stage and grade,tumor site in the colon,ploidy status,and patient smoking status.This study aimed to evaluate current evidence regarding the diagnostic power of CEA levels in the early detection of CRC recurrence in adults.AIM To evaluate current evidence regarding the diagnostic power of CEA levels in the early detection of CRC recurrence in adults.METHODS A systematic search was performed using four databases:MEDLINE,Cochrane Trials,EMBASE,and the Web of Science.The inclusion criteria were as follows:Adult patients aged≥18 years who had completed CRC curative treatment and were followed up postoperatively;reporting the number of CRC recurrences as an outcome;and randomized,clinical,cohort,and case-control study designs.Studies that were not published in English and animal studies were excluded.The following data were extracted by three independent reviewers:Study design,index tests,follow-up,patient characteristics,and primary outcomes.All statistical analyses were performed using the RevMan 5.4.1.RESULTS A total of 3232 studies were identified,with 73 remaining following the elimination of duplicates.After screening on predetermined criteria,12 studies were included in the final analysis.At a reference standard of 5 mg/L,CEA detected only approximately half of recurrent CRCs,with a pooled sensitivity of 59%(range,33%–83%)and sensitivity of 89%(range,58%–97%).CONCLUSION CEA is a significant marker for CRC diagnosis.However,it has insufficient sensitivity and specificity to be used as a single biomarker of early CRC recurrence,with an essential proportion of false negatives.展开更多
BACKGROUND Gastric cancer(GC)is a common malignant tumor of the digestive system with a high degree of malignancy.It usually develops insidiously without any specific symptoms in the early stages.As one of the disease...BACKGROUND Gastric cancer(GC)is a common malignant tumor of the digestive system with a high degree of malignancy.It usually develops insidiously without any specific symptoms in the early stages.As one of the diseases caused by abnormal gene changes,GC has abnormal expression of various oncogenes and products during its development.Tumor markers such as carcinoembryonic antigen(CEA),carbohydrate antigen 199(CA199)and carbohydrate antigen 724(CA724)are not expressed or lowly expressed in normal people,but significantly increased after carcinogenesis.Monitoring the changes in the levels of tumor markers such as CEA,CA199 and CA724 is conducive to early diagnosis and evaluation of the occurrence of some solid tumors.AIM To investigate the expression of CEA,CA199 and CA724 in GC and their correlation with clinical features,hoping to provide more effective markers for the early preventive diagnosis of GC.METHODS Of 87 patients with GC admitted to our hospital from September 2020 to December 2021 were included in the GC group,and another 80 healthy people who came to our hospital for physical examination with normal results during the same period were selected as the control group.The serum CEA,CA199,and CA724 levels were compared between the two groups,and the serum CEA,CA199,and CA724 levels were compared in patients with GC at different TNM stages,and the differences in the positive rates of CEA,CA199,and CA724 alone and in combination in detecting TNM stages of GC and GC were compared.In addition,the relationship between the levels of tumor markers CEA,CA199 and CA724 and the clinicopathological characteristics of GC patients was also analyzed.The relationship between the serum levels of CEA,CA199 and CA724 and the survival period of GC patients was analyzed by Pearson.RESULTS The serum levels of CEA,CA199 and CA724 in GC group were significantly higher than those in control group(P<0.05).With the increase of TNM stage,the serum CEA,CA199 and CA724 expression levels in GC patients increased significantly,and the differences between groups were statistically significant(P<0.05).The positive rate of the CA724 single test was higher than that of CEA and CA199 single test(P<0.05).The positive rate of the three combined tests was 95.40%(83/87),which was higher than that of CEA,CA199 and CA724 single tests.The difference was statistically significant(P<0.05).The combined detection positive rates of CEA,CA199,and CA724 in stages I,II,III,and IV of GC were 89.66%,93.10%,98.85%,and 100.00%respectively,all of which were higher than the individual detection rates of CEA,CA199,and CA724.The differences were statistically significant(P<0.05).There was no significant difference in serum CEA,CA199 and CA724 levels between GC patients with different genders,smoking history and alcohol history(P>0.05).However,the serum CEA,CA199 and CA724 levels were significantly higher in GC patients aged≥45 years,TNM stage III-IV,with lymph node metastasis and tumor diameter≥5 cm than in GC patients aged<45 years,TNM stage I-II,without lymph node metastasis and tumor diameter<5 cm(P<0.05).CONCLUSION The expression levels of serum tumor markers CEA,CA199 and CA724 in patients with GC are high and rise with the increase of TNM stage.The levels of CEA,CA199 and CA724 are related to age,TNM stage,lymph node metastasis and tumor diameter.The combined detection of CEA,CA199 and CA724 is helpful to improve the diagnostic accuracy of GC with high clinical guidance value.展开更多
BACKGROUND Carcinoembryonic antigen(CEA)is a broad-spectrum tumor marker for differential diagnosis,monitoring,and response assessment of a variety of malignancies.AIM To evaluate whether serum CEA could predict the p...BACKGROUND Carcinoembryonic antigen(CEA)is a broad-spectrum tumor marker for differential diagnosis,monitoring,and response assessment of a variety of malignancies.AIM To evaluate whether serum CEA could predict the prognosis in patients with colorectal cancer liver metastasis(CRCLM)before and after liver resection(LR).METHODS PubMed,Embase,Cochrane,and Web of Science were systematically searched to retrieve literature,with a search cut-off date of February 27,2023.Articles were strictly screened for inclusion according to pre-specified inclusion and exclusion criteria.Data were pooled and analyzed using Stata 16.0.RESULTS This meta-analysis included 36 studies involving a total of 11143 CRCLM patients.The results showed that a high pre-LR serum CEA level was correlated with poor overall survival(OS)[hazard ratio(HR)=1.61,95%confidence interval(CI):1.49-1.75,P<0.001]and recurrence-free survival(HR=1.27,95%CI:1.11-1.45,P<0.001)in CRCLM patients.A high post-LR serum CEA level predicted poor OS(HR=2.66,95%CI:2.10-3.38,P<0.001).A comparison by treatment modality,analysis modality,patient source,and cutoff-value showed that overall,high preoperative and postoperative serum CEA levels remained correlated with a poor prognosis.CONCLUSION This study concluded that high pre-LR and post-LR serum CEA levels were significantly correlated with a poor prognosis in CRCLM patients.展开更多
BACKGROUND Preoperative chemoradiotherapy(CRT)is a standard treatment modality for locally advanced rectal cancer.However,CRT alone cannot improve overall survival.Approximately 20%of patients with CRT-resistant tumor...BACKGROUND Preoperative chemoradiotherapy(CRT)is a standard treatment modality for locally advanced rectal cancer.However,CRT alone cannot improve overall survival.Approximately 20%of patients with CRT-resistant tumors show disease progression.Therefore,predictive factors for treatment response are needed to identify patients who will benefit from CRT.We theorized that the prognosis may vary if patients are classified according to pre-to post-CRT changes in carcinoembryonic antigen(CEA)levels.AIM To identify patients with locally advanced rectal cancer for preoperative chemoradiotherapy based on carcinoembryonic antigen levels.METHODS We retrospectively included locally advanced rectal cancer patients who underwent preoperative CRT and curative resection between 2011 and 2017.Patients were assigned to groups A,B,and C based on pre-and post-CRT serum CEA levels:Both>5;pre>5 and post≤5;and both≤5 ng/mL,respectively.We compared the response to CRT based on changes in serum CEA levels.Receiver operating characteristic curve analysis was performed to determine optimal cutoff for neutrophil–lymphocyte ratio and platelet–lymphocyte ratio.Multivariate logistic regression analysis was used to evaluate the prognostic factors for pathologic complete response(pCR)/good response.RESULTS The cohort comprised 145 patients;of them,27,43,and 65 belonged to groups A,B,and C,respectively,according to changes in serum CEA levels before and after CRT.Pre-(P<0.001)and post-CRT(P<0.001)CEA levels and the ratio of downstaging(P=0.013)were higher in Groups B and C than in Group A.The ratio of pathologic tumor regression grade 0/1 significantly differed among the groups(P=0.003).Group C had the highest number of patients showing pCR(P<0.001).Most patients with pCR showed pre-and post-CRT CEA levels<5 ng/mL(P<0.001,P=0.008).Pre-and post-CRT CEA levels were important risk factors for pCR(OR=18.71;95%CI:4.62–129.51,P<0.001)and good response(OR=5.07;95%CI:1.92–14.83,P=0.002),respectively.Pre-CRT neutrophil–lymphocyte ratio and post-CRT T≥3 stage were also prognostic factors for pCR or good response.CONCLUSION Pre-and post-CRT CEA levels,as well as change in CEA levels,were prognostic markers for treatment response to CRT and may facilitate treatment individualization for rectal cancer.展开更多
AIM: To evaluate the serum levels of cytokeratins and carcinoembryonic antigen (CEA) in diagnosis, staging and prognosis of patients with colorectal adenocarcinoma.METHODS: The sample consisted of 169 patients. One hu...AIM: To evaluate the serum levels of cytokeratins and carcinoembryonic antigen (CEA) in diagnosis, staging and prognosis of patients with colorectal adenocarcinoma.METHODS: The sample consisted of 169 patients. One hundred blood donors formed the control group. Radical surgery was performed on 120 patients, with an average follow-up duration of 22.3 mo. Relapses occurred in 23individuals after an average of 18.09 mo. CEA was assayed via the Delfia(R) method with a limit of 5 ng/mL. Cytokeratins were assayed via the LIA-mat(R) TPA-M Prolifigen(R) method with a limit of 72 U/L.RESULTS: In the diagnosis of patients with colorectal adenocarcinoma, CEA showed a sensitivity of 56%, a specificity of 95%, a positive predictive value of 94%, a negative predictive value of 50% and an accuracy of 76.8%.TPA-M had a sensitivity of 70%, a specificity of 96%, a positive predictive value of 97%, a negative predictive value of 66% and an accuracy of 93.6%. The elevation of one of the markers was shown to have a sensitivity of 76.9%, a specificity of 91%, a positive predictive value of 93.5%, a negative predictive value of 70% and an accuracy of 83.6%.There was no variation in the levels of the markers according to the degree of cell differentiation while there was an elevation in their concentrations in accordance with the increase in neoplastic dissemination. There was a statistically significant difference between the patients with stage Ⅳ lesions and those with stages Ⅰ, Ⅱ and Ⅲ tumors.With regard to CEA, the averagelevel was 14.2 ng/mL in patients with stage Ⅰ lesions, 8.5 ng/mL in patients with stage Ⅱ lesions, 8.0 ng/mL in patients with stage Ⅲ lesions and 87.7 ng/mL in patients with stage Ⅳ lesions. In relation to TPA-M, the levels were 153.1 U/L in patients with stage Ⅰtumors, 106.5 U/L in patients with stage Ⅱ tumors, 136.3 U/L in patients with stage Ⅲ tumors and 464.3 U/L in patients with stage Ⅳ tumors. There was a statistical difference in patients with a high CEA level in relation to a shorter survival(P＜0.05). However, there was no correlation between patients with high TPA-M levels and prognostic indices of patients undergoing radical surgery.CONCLUSION: Cytokeratins demonstrate a greater sensitivity than CEA in the diagnosis of colorectal adenocarcinoma.There is an increase in the sensitivity of the markers with tumor dissemination. Cytokeratins cannot identify the worse prognosis in patients undergoing radical surgery.Cytokeratins constitute an advance in the direction of a perfect tumor marker in the treatment of patients with colorectal cancer.展开更多
BACKGROUND Carcinoembryonic antigen(CEA)is a commonly used biomarker in colorectal cancer.However,controversy exists regarding the insufficient prognostic value of preoperative serum CEA alone in rectal cancer.Here,we...BACKGROUND Carcinoembryonic antigen(CEA)is a commonly used biomarker in colorectal cancer.However,controversy exists regarding the insufficient prognostic value of preoperative serum CEA alone in rectal cancer.Here,we combined preoperative serum CEA and the maximum tumor diameter to correct the CEA level,which may better reflect the malignancy of rectal cancer.AIM To assess the prognostic impact of preoperative CEA/tumor size in rectal cancer.METHODS We retrospectively reviewed 696 stage I to III rectal cancer patients who underwent curative tumor resection from 2007 to 2012.These patients were randomly divided into two cohorts for cross-validation:training cohort and validation cohort.The training cohort was used to generate an optimal cutoff point and the validation cohort was used to further validate the model.Maximally selected rank statistics were used to identify the optimum cutoff for CEA/tumor size.The Kaplan-Meier method and log-rank test were used to plot the survival curve and to compare the survival data.Univariate and multivariate Cox regression analyses were used to determine the prognostic value of CEA/tumor size.The primary and secondary outcomes were overall survival(OS)and disease-free survival(DFS),respectively.RESULTS In all,556 patients who satisfied both the inclusion and exclusion criteria were included and randomly divided into the training cohort(2/3 of 556,n=371)and the validation cohort(1/3 of 556,n=185).The cutoff was 2.429 ng/mL per cm.Comparison of the baseline data showed that high CEA/tumor size was correlated with older age,high TNM stage,the presence of perineural invasion,high CEA,and high carbohydrate antigen 19-9(CA 19-9).Kaplan-Meier curves showed a manifest reduction in 5-year OS(training cohort:56.7%vs 81.1%,P<0.001;validation cohort:58.8%vs 85.6%,P<0.001)and DFS(training cohort:52.5%vs 71.9%,P=0.02;validation cohort:50.3%vs 79.3%,P=0.002)in the high CEA/tumor size group compared with the low CEA/tumor size group.Univariate and multivariate analyses identified CEA/tumor size as an independent prognostic factor for OS(training cohort:hazard ratio(HR)=2.18,95%confidence interval(CI):1.28-3.73,P=0.004;validation cohort:HR=4.83,95%CI:2.21-10.52,P<0.001)as well as DFS(training cohort:HR=1.47,95%CI:0.93-2.33,P=0.096;validation cohort:HR=2.61,95%CI:1.38-4.95,P=0.003).CONCLUSION Preoperative CEA/tumor size is an independent prognostic factor for patients with stage I-III rectal cancer.Higher CEA/tumor size is associated with worse OS and DFS.展开更多
AIM:To identify the predictors of distant metastasis in pathologically T1(pT1)colorectal cancer(CRC)after radical resection. METHODS:Variables including age,gender,preoperative carcinoembryonic antibody(CEA)level,tumo...AIM:To identify the predictors of distant metastasis in pathologically T1(pT1)colorectal cancer(CRC)after radical resection. METHODS:Variables including age,gender,preoperative carcinoembryonic antibody(CEA)level,tumor location,tumor size,lymph node status,and histological grade were recorded.Patients with and without metastasis were compared with regard to age,gender,CEA level and pathologic tumor characteristics using the independent t test orχ 2 test,as appropriate.Risk factors were determined by logistic regression analysis. RESULTS:Metastasis occurred in 6(3.8%)of the 159 patients during a median follow-up of 67.0(46.5%) mo.The rates of distant metastasis in patients with pT1 cancer of the colon and rectum were 6.7%and 2.9%, respectively(P<0.001).The rates of distant metastasis between male and female patients with T1 CRC were 6.25%and 1.27%,respectively(P<0.001).The most frequent site of distant metastasis was the liver. Age(P=0.522),gender(P=0.980),tumor location(P =0.330),tumor size(P=0.786),histological grade(P =0.509),and high serum CEA level(P=0.262)were not prognostic factors for lymph node metastasis.Univariate analysis revealed that age(P=0.231),gender(P =0.137),tumor location(P=0.386),and tumor size (P=0.514)were not risk factors for distant metastasis after radical resection for T1 colorectal cancer.Postoperative metastasis was only significantly correlated with high preoperative serum CEA level(P=0.001).Using multivariate logistic regression analysis,high preoperative serum CEA level(P=0.004;odds ratio 15.341; 95%CI 2.371-99.275)was an independent predictor for postoperative distant metastasis. CONCLUSION:The preoperative increased serum CEA level is a predictive risk factor for distant metastasis in CRC patients after radical resection.Adjuvant chemotherapy may be necessary in such patients,even if they have pT1 colorectal cancer.展开更多
AIM To assess whether elevated serum carcinoembryonic antigen(CEA) is in the inferior prognosis for pathological lymph node-negative(p N_0) gastric cancer(GC) patients who underwent D_2 gastrectomy.METHODS About 469 p...AIM To assess whether elevated serum carcinoembryonic antigen(CEA) is in the inferior prognosis for pathological lymph node-negative(p N_0) gastric cancer(GC) patients who underwent D_2 gastrectomy.METHODS About 469 p N0 GC patients,who received D^2 radical gastrectomy were retrospectively analyzed. The X-tile plots cut-off point for CEA were 30.02 ng/m L using minimum P-value from log-rank χ~2 statistics,and p N_0 GC patients were assigned to two groups: those more than 30.02 ng/m L(n = 48;CEA-high group) and those less than 30.02 ng/m L(n = 421;CEA-low group). Clinicopathologic characteristics were compared usingPearson's χ2 or Fisher's exact tests,and survival curves were so manufactured using the Kaplan-Meier method. Univariate and multivariate analysis were carried out using the logistic regression method.RESULTS The percentage of vessel carcinoma embolus(31.35% vs 17.1%) and advanced GC(T_(2-4b))(81.25% vs 65.32%) were higher in CEA-high group than CEA-low group. The CEA-positive patients had a significantly poorer prognosis than the CEA-nagetive patients in terms of overall survival(57.74% vs 90.69%,P < 0.05),and no different was found between subgroup of T category,differentiation,nerve invasion,and vessel carcinoma embolus(all P > 0.05). Multivariate survival analysis showed that CEA(OR = 4.924),and T category(OR = 2.214) were significant prognostic factors for stage p N0 GC(all P < 0.05). Besides,only T category(OR = 1.962) was an independent hazard factor in the CEA-high group(P < 0.05).CONCLUSION Those pretreatment serum CEA levels over 30.02 ng/m L on behalf of worse characteristics and unfavourable tumor behavior,and a poor prognosis for a nearly doubled risk of mortality in GC patients.展开更多
AIM:To evaluate the value of positron emission tomography(PET)/computerized tomography(CT)in surveillance of colorectal cancer(CRC)patients with different carcinoembryonic antigen(CEA)concentrations.METHODS:One hundre...AIM:To evaluate the value of positron emission tomography(PET)/computerized tomography(CT)in surveillance of colorectal cancer(CRC)patients with different carcinoembryonic antigen(CEA)concentrations.METHODS:One hundred and six postoperative CRC patients who had suspected recurrence or metastasis and received fluorodeoxyglucose(FDG)PET/CT within one week were included in this study.The final diagnosis was confirmed by histological examination or clinicalfollow-up over at least six months.RESULTS:The sensitivity,specificity,and accuracy of FDG PET/CT were 95.2%,82.6%,and 92.5%,and94.8%,81.4%and 92.8%,respectively,in the caseand lesion-based analyses.The sensitivity and accuracy of FDG PET/CT significantly differed from CT in both analyses(χ2=8.186,P=0.004;χ2=6.201,P=0.013;χ2=13.445,P=0.000;χ2=11.194,P=0.001).In the lesion-based analysis,the sensitivity,specificity,and accuracy of FDG PET/CT in the abnormal CEA group were97.8%,82.6%,and 95.6%,compared with 81.3%,80%,and 80.6%for patients with normal CEA levels.In case-based analysis,the sensitivity,specificity,and accuracy of FDG PET/CT were 97.2%,77.8%,and 95%in abnormal CEA group.Only in lesion-based analysis,the sensitivity and accuracy of FDG PET/CT in the abnormal CEA group were significantly superior to those in the normal CEA group(χ2=6.432,P=0.011;χ2=7.837,P=0.005).FDG PET/CT changed the management in 45.8%of patients with positive scans.CONCLUSION:FDG PET/CT showed superior diagnostic value and is an advisable option in surveillance of postoperative CRC patients with a vague diagnosis.展开更多
AIM: To evaluate outcomes in resectable cholangiocarcinoma patients and to determine prognostic factors. METHODS: A retrospective study was conducted among newly-diagnosed cholangiocarcinoma patients from January 2009...AIM: To evaluate outcomes in resectable cholangiocarcinoma patients and to determine prognostic factors. METHODS: A retrospective study was conducted among newly-diagnosed cholangiocarcinoma patients from January 2009 to December 2011 who underwent curative resection in Srinakarind Hospital (a 1000-bed university hospital). Two hundred and sixty-three cholangiocarcinoma patients with good performance were enrolled. These patients had pathological reports with clear margins or microscopic margins. Prognostic factors which included clinical factors, serum liver function test as well as serum tumor makers at presentation,tumor data, and receiving adjuvant chemotherapy were determined by uniand multivariate analysis. RESULTS: The median overall survival time was 17 mo (95%CI: 13.2-20.7); and 1-, 2-, and 3year survival rates were 65.5%, 45.2% and 35.4%. Serum albumin levels, serum carcinoembryonic antigen (CEA) levels, staging classifications by American Joint Committee on cancer, pathological tumor staging, lymph node metastases, tumor grading, surgical margin status, and if adjuvant chemotherapy was administered, were shown to be significant prognostic factors of resectable cholangiocarcinoma by univariate analysis. Multivariate analysis, however, established that only abnormal serum CEA [hazard ratio (HR) 1.68; P = 0.027] and lymph node metastases (HR 2.27; P = 0.007) were significantly associated with a decrease in overall survival, while adjuvant chemotherapy (HR 0.71; P = 0.067) and surgical margin negative (HR 0.72; P = 0.094) tended to improve survival time. CONCLUSION: Serum CEA and lymph node metastases which were associated with advanced stage tumors become strong negative prognostic factors in cholangiocarcinoma.展开更多
AIM: To investigate the impact of RAS and BRAF mutations on the pattern of metastatic disease and carcinoembryonic antigen(CEA) production.METHODS: In this retrospective study, we investigated the impact of RAS and BR...AIM: To investigate the impact of RAS and BRAF mutations on the pattern of metastatic disease and carcinoembryonic antigen(CEA) production.METHODS: In this retrospective study, we investigated the impact of RAS and BRAF mutational status on pattern of metastatic disease and CEA production. Only patients presenting with a newly diagnosed metastatic colorectal cancer(CRC) were included. Patients' characteristics, primary tumor location, site of metastatic disease and CEA at presentation were compared between those with and without RAS and BRAF mutations.RESULTS: Among 174 patients, mutations in KRAS, NRAS and BRAF were detected in 47%, 3% and 6% respectively. RAS mutations(KRAS and NRAS) were more likely to be found in African American patients(87% vs 13%; P value = 0.0158). RAS mutations were associated with a higher likelihood of a normal CEA(< 5 ng/mL) at presentation. BRAF mutations were more likely to occur in females. We were not able to confirm any association between mutational status and site of metastatic disease at initial diagnosis.CONCLUSION: No association was found between RAS and BRAF mutations and sites of metastatic disease at the time of initial diagnosis in our cohort. Patients with RAS mutations were more likely to present with CEA levels < 5 ng/mL. These findings may have clinical implications on surveillance strategies for RAS mutant patients with earlier stages of CRC.展开更多
Pancreatic cystic lesions(PCLs) have been increasingly recognized in clinical practice. Although inflammatory cysts(pseudocysts) are the most common PCLs detected by cross-sectional imaging modalities in symptomatic p...Pancreatic cystic lesions(PCLs) have been increasingly recognized in clinical practice. Although inflammatory cysts(pseudocysts) are the most common PCLs detected by cross-sectional imaging modalities in symptomatic patients in a setting of acute or chronic pancreatitis, incidental pancreatic cysts with no symptoms or history of pancreatitis are usually neoplastic cysts. For these lesions,it is imperative to identify mucinous cysts(intraductal papillary mucinous neoplasms and mucinous cystic neoplasms) due to the risk of their progression to malignancy. However, no single imaging modality alone is sufficient for a definitive diagnosis of all PCLs. The cyst fluid obtained by endoscopic ultrasound-guided fine needle aspiration provides additional information for the differential diagnosis of PCLs. Current recommendations suggest sending cyst fluid for cytology evaluation and measurement of carcinoembryonic antigen(CEA) levels. Unfortunately, the sensitivity of cytology is greatly limited, and cyst fluid CEA has demonstrated insufficient accuracy as a predictor of mucinous cysts. More recently, cyst fluid glucose has emerged as an alternative to CEA for distinguishing between mucinous and nonmucinous lesions. Herein, the clinical utility of cyst fluid glucose and CEA for the differential diagnosis of PCLs was evaluated.展开更多
Objective: To identify prognostic factors in patients with locally advanced cervical cancer treated with concurrent chemoradiotherapy (CCRT). Methods and Materials: We analyzed 76 patients with FIGO stage IB2 - IVb ce...Objective: To identify prognostic factors in patients with locally advanced cervical cancer treated with concurrent chemoradiotherapy (CCRT). Methods and Materials: We analyzed 76 patients with FIGO stage IB2 - IVb cervical cancer treated with CCRT between 2001 and 2006 at the Nagoya University Hospital. Patients with an advanced cervical cancer treated with CCRT. Overall survival (OS) and Progression-free survival (PFS) rates were estimated using the Kaplan-Meier method. The log-rank test was used to test differences in survival. Fisher's exact test was employed for univariate analysis. The Cox proportional hazard model was used for multivariate analysis. Results: The median age was 52, and the median follow-up period was 36 months. The 5 - year OS and PFS rates of all patients were 88.2% and 72.4%, respectively. Twenty-one of the 76 patients were diagnosed with recurrence. A higher serum CEA before CCRT was an independent predictive factor for a poor prognosis on multivariate analysis. Conclusions: A high level of serum CEA was a predictive factor for a poor prognosis. New strategies should be considered to control disease in this group of patients.展开更多
Objective This study aimed to evaluate serum and nipple discharge levels of carcinoembryonic antigen(CEA) and cancer antigen 153(CA153) and tissue cyclooxygenase-2(COX-2) expression in breast cancer cases and associat...Objective This study aimed to evaluate serum and nipple discharge levels of carcinoembryonic antigen(CEA) and cancer antigen 153(CA153) and tissue cyclooxygenase-2(COX-2) expression in breast cancer cases and associations of these proteins with breast cancer metastasis.Methods The immunohistochemical Ultra Sensitive^(TM) S-P method was used to detect COX-2 expression in 77 cases of invasive breast carcinoma. Of these cases, 52 exhibited CEA and CA153 in both serum and nipple discharge(electrochemiluminescence method), and associations of these biomarkers with breast cancer prognosis were studied. Sixty cases of benign breast lesion were selected as a control group. Overall survival of breast carcinoma patients was evaluated. COX-2 expression was evaluated relative to clinicopathological features and CEA and CA153 levels, and its role in invasiveness was investigated.Results Among cases of invasive breast cancer, 72.7%(56/77) were COX-2 immunopositive, compared to 16.7% of benign lesions(χ2 = 66.745, P = 0.000) percentage of positive cells. COX-2 overexpression in breast cancer correlated positively with histological grade(II vs III; χ2 = 4.064, P = 0.043), lymph node metastasis(χ2 = 9.135, P = 0.003), and distant metastasis(χ2 = 8.021, P = 0.003). However, COX-2 expression did not correlate with age(≤ 50 vs 50 years) or tumor size(≤ 5 vs > 5 cm)(χ2 = 0.081, P = 0.776 and χ2 = 3.702, P = 0.054, respectively). Among breast cancer patients, COX-2 overexpression in tumors also correlated with shorter overall survival(P < 0.05). In brief, increased COX-2 expression correlates with worse prognosis and shorter overall survival. Malignant lesions were associated with significantly higher serum and nipple discharge levels of biomarkers, relative to benign lesions(P < 0.05). These biomarkers were present at significantly higher levels in nipple discharge than in serum(P < 0.05). Furthermore, significantly higher nipple discharge levels of CEA and CA153 were observed in COX-2-positive breast carcinoma patients, compared to COX-2-negative patients(P <0.05). Shorter overall survival in cancer patients group related to COX-2 overexpression in tumors(P < 0.05).Conclusion The study suggests that COX-2 overexpression correlates with poor clinicopathological parameters in breast cancers and might be an important biological marker of invasion and metastasis. The findings of the present study suggest that combined detection of COX-2 tissue expression and CEA and CA153 in serum and nipple discharge could facilitate clinical monitoring and diagnosis of metastasis in patients with breast cancer.展开更多
BACKGROUND Carcinoembryonic antigen(CEA)is an important serum tumour marker with a substantial role in diagnosis and monitoring of various solid tumours.About 36%-70%of breast cancers have elevated serum CEA.And the a...BACKGROUND Carcinoembryonic antigen(CEA)is an important serum tumour marker with a substantial role in diagnosis and monitoring of various solid tumours.About 36%-70%of breast cancers have elevated serum CEA.And the available studies show discrepancy in addressing the prognostic significance of CEA in advanced breast cancer.AIM To estimate the serum CEA level in our metastatic breast cancer patients and correlate it with response to treatment and clinical outcome.METHODS This was a prospective clinical study conducted on 50 metastatic breast cancer patients treated at breast clinic,with newly diagnosed metastatic breast cancer planned for palliative chemotherapy,targeted therapy,and hormonal treatment.We estimated the proportion of patients with elevated serum CEA level at baseline and after palliative treatment and also studied the association of serum CEA levels with known prognostic factors.The response to treatment was correlated with the serum CEA levels in the context of responders and nonresponders.RESULTS The median pre-treatment and post-treatment CEA levels were 7.9(1.8-40.7)ng/mL and 4.39(1.4-12.15)ng/mL,respectively,in the whole study population(P=0.032).No statistically significant difference was seen in baseline serum CEA between responders and non-responders.Even in the luminal group,pretreatment serum CEA was not a predictor of response,but post-treatment CEA was a significant predictor of tumour progression.In patients with liver and lung metastases,post-treatment CEA level difference was not statistically significant in both responders and non-responders though the values were higher in nonresponders.Among those with bone metastases,69.5%had elevated post-treatment serum CEA,and only 37.5%had elevated serum CEA in those with no bone metastases.CONCLUSION Elevated post-treatment serum CEA levels are associated with disease progression and poor response to therapy.Persistently elevated post-treatment serum CEA levels are significantly associated with bone metastases.Elevated serum CEA and hormonal status are significant predictors of treatment response.展开更多
Aim: The objective of this study was to investigate the prognostic value of serum carcinoembryonic antigen (CEA) level in colorectal cancer patients with liver metastases. The serum CEA level was recorded at the point...Aim: The objective of this study was to investigate the prognostic value of serum carcinoembryonic antigen (CEA) level in colorectal cancer patients with liver metastases. The serum CEA level was recorded at the point of metastasis diagnosis, differing from the majority of literature looking at preoperative metastasectomy CEA level. Methods: From January 2010 to December 2014, 138 patients with a diagnosis of colorectal cancer and liver metastases were included in the study—population from Buenos Aires, Argentina. Patients with both resectable and unresectable liver metastases were followed up over a 4-year period. Kaplan Meier survival analysis was used to produce survival curves that were compared by log-rank test. Results: The overall survival for all patients studied with a CEA < 100 ng/ml was significantly longer compared to patients with CEA ≥ 100 ng/mL (p < 0.001). The 1-, 2-, and 3-year overall survival rates for the whole cohort were 73.6, 56.6 and 53.8% respectively. For patients with unresectable metastases, a low CEA level (<100 ng/mL) was also associated with the increased overall survival (p = 0.036). Conclusions: In our patient cohort, this study indicated that a low CEA level (<100 ng/mL) measured at metastasis diagnosis was a good prognostic indicator for improving survival in patients with colorectal liver metastases. These findings highlight the importance of measuring serum CEA levels in this group of patients at the time of liver metastasis diagnosis.展开更多
The long-term success of gene therapy for cancer relies heavily on the deveiopment of effective targeting systems. We investigate the possibility of targeted gene therapy using promoter of carcinoembryonic antigen (CE...The long-term success of gene therapy for cancer relies heavily on the deveiopment of effective targeting systems. We investigate the possibility of targeted gene therapy using promoter of carcinoembryonic antigen (CEA) gene. By using luciferase reporter gene, we found that CEA promoter exhibit 16 times high activity in CEA-producing lung cancer cells, A549 than in nonproducing cells, Hela. We also constructed a recombinant expression plasmid pCEATK, in which CEA promoter drives the effector gene, thymidine ki-nase gene of Herpes Simplex Virus (HSVTK). A549 cells transfected with pCEATK became 865 times more sensitive to ganclclovir (GCV) than the control cells. However, Hela cells transfected with this plasmid re-mained resistant to GCV. These data indicate the potential for targeted gene therapy using the CEA promoter against CEA-producing tumor cells, suck as lung cancer cells.展开更多
Objective:Lymphatic endothelial cell(LEC)proliferation is essential for lymphangiogenesis.Hypoxia induces lymphangiogenesis,but it directly inhibits LEC proliferation and the underlying mechanisms have not been fully ...Objective:Lymphatic endothelial cell(LEC)proliferation is essential for lymphangiogenesis.Hypoxia induces lymphangiogenesis,but it directly inhibits LEC proliferation and the underlying mechanisms have not been fully understood.The aim of this study was to investigate the role of carcinoembryonic antigen-related cell adhesion molecule 1(CEACAM1)in hypoxia-repressed LEC proliferation.Methods:Human dermal lymphatic endothelial cells(HDLECs)were cultured under normoxic or hypoxic conditions,and cell proliferation was determined using MTT or CCK-8 assays.CEACAM1 expression was silenced by siRNA transfection.Activation of mitogen-activated protein kinases(MAPKs)was examined by Western blotting and blocked by specific inhibitors.Results:Under hypoxia,HDLECs proliferation was suppressed and CEACAM1 expression was downregulated.Silence of CEACAM1 in normoxia inhibited HDLECs proliferation and did not further decrease proliferation in HDLECs in response to hypoxia,suggesting that CEACAM1 may mediate hypoxia-induced inhibition of HDLECs proliferation.In addition,silence of CEACAM1 increased phosphorylation of MAPK molecules:extracellular signal-regulated kinase(ERK),p38 MAPK and Jun N-terminal kinase(JNK)in HDLECs.However,only inhibition of the JNK pathway rescued the reduction of HDLEC proliferation induced by CEACAM1 silence.Conclusion:Our results suggested that hypoxia downregulates CEACAM1 expression by activation of the JNK pathway,leading to inhibition of HDLEC proliferation.These findings may help to understand the mechanisms of LEC-specific response to hypoxia and develop novel therapies for pathological lymphangiogenesis.展开更多
Objective: To study the preparation and characterization of monoclonal antibody (McAb) against carcinoembryonic antigen (CEA). Methods: CEA antigen was extracted from metastasized liver of patients with colorectal can...Objective: To study the preparation and characterization of monoclonal antibody (McAb) against carcinoembryonic antigen (CEA). Methods: CEA antigen was extracted from metastasized liver of patients with colorectal cancer and used for the preparation of McAb against CEA by hybridoma technique. Immunoreactivity of McAb to CEA antigen was evaluated using ELISA. Mouse ascites was purified by two steps, high performance liquid chromatography (HPLC) using protein A and high performance hydroxylapatite (HPHT). Normal adult tissues and tumor specimen were used for immunohistochemical evaluation of the McAb. Isotope 99mTc labeled CEA McAb was used for biodistribution in tumor-bearing mouse. Results: Purified CEA antigen was a glycoprotein of 180 kD. Anti-CEA McAb affinity constant was 7.4x109/M. The McAb showed positive staining in 54-88% of colorectal cancer, gastric cancer and lung cancer, while negative for normal tissues. 24 hours after injection of 99mTc labeled McAb, tumor ID%/g was higher than 15% and tumor/blood, tumor/kidney and tumor/liver were 1.82, 1.51 and 2.92 respectively. T/NT ratios of other viscera were over 3.0. Conclusion: Purified CEA antigen had very good immunogenicity. The anti-CEA McAb was highly specific. 99mTc labeled McAb was stabled both in vivo and in vitro. In vivo distribution result was satisfactory. McAb CL58 may be useful for RII and RIGS.展开更多
Objective: To investigate the relationship betwhen production of carcinoembryonic antigen (CEA) in thehuman cells of different tissues and scquence variation of t CEA promoter in the cellular genomes. and evaluate po-...Objective: To investigate the relationship betwhen production of carcinoembryonic antigen (CEA) in thehuman cells of different tissues and scquence variation of t CEA promoter in the cellular genomes. and evaluate po-tential application of the ets active scqucnce of CEA gene in colorectal carcinoma tissie-specific gene therapy.Methods: Nested-polymerase chain reaction (PCR) was employed to amplify the CEA promoter sequences fromthe genome of human colorectal carcinoma. normal adjacent colonic mucosa tissues. normal blood cells. placentatissues and some established cell lines of human origin. PCR-Southern bloting assay was utilized to define the reliability of the amplified sequences. The scquence variations were evaluated by means of PCR-single stranded conformation polymorphism (PCR-SSCP) and DNA sequencing. Binding effect of the amplified fragment was examinedby Band-Shift assay. Results: No scqucnce variation was found between-135bp and+69bp from the transcription-al initiation site. which was considered to be a core region of CEA promoter. There was no correlativity betweenproduction levels of CEA and sequence variations of CEA gene promoter core region. The fragment amplified either from normal tissues or from colorectal carcinoma tissues could equally bind with the nuclear extract from Lo-Vo cells. Conclusion: Differential level of CEA gene transcription in the colorectal carcinoma cells. as comparedwith normal tissues, was proved not to be related to the sequence variation of CEA promoter core region. CEApromoters, either from normal cellular genome or neoplasm cellular genome. were found suitable for colorectalcarcinoma tissue-specific gene therapy.展开更多
文摘BACKGROUND Colorectal cancer(CRC)is a prevalent malignant tumor involving adenomas that develop into malignant lesions.Carcinoembryonic antigen(CEA)is a non-specific serum biomarker upregulated in CRC.The concentration of CEA is modulated by tumor stage and grade,tumor site in the colon,ploidy status,and patient smoking status.This study aimed to evaluate current evidence regarding the diagnostic power of CEA levels in the early detection of CRC recurrence in adults.AIM To evaluate current evidence regarding the diagnostic power of CEA levels in the early detection of CRC recurrence in adults.METHODS A systematic search was performed using four databases:MEDLINE,Cochrane Trials,EMBASE,and the Web of Science.The inclusion criteria were as follows:Adult patients aged≥18 years who had completed CRC curative treatment and were followed up postoperatively;reporting the number of CRC recurrences as an outcome;and randomized,clinical,cohort,and case-control study designs.Studies that were not published in English and animal studies were excluded.The following data were extracted by three independent reviewers:Study design,index tests,follow-up,patient characteristics,and primary outcomes.All statistical analyses were performed using the RevMan 5.4.1.RESULTS A total of 3232 studies were identified,with 73 remaining following the elimination of duplicates.After screening on predetermined criteria,12 studies were included in the final analysis.At a reference standard of 5 mg/L,CEA detected only approximately half of recurrent CRCs,with a pooled sensitivity of 59%(range,33%–83%)and sensitivity of 89%(range,58%–97%).CONCLUSION CEA is a significant marker for CRC diagnosis.However,it has insufficient sensitivity and specificity to be used as a single biomarker of early CRC recurrence,with an essential proportion of false negatives.
文摘BACKGROUND Gastric cancer(GC)is a common malignant tumor of the digestive system with a high degree of malignancy.It usually develops insidiously without any specific symptoms in the early stages.As one of the diseases caused by abnormal gene changes,GC has abnormal expression of various oncogenes and products during its development.Tumor markers such as carcinoembryonic antigen(CEA),carbohydrate antigen 199(CA199)and carbohydrate antigen 724(CA724)are not expressed or lowly expressed in normal people,but significantly increased after carcinogenesis.Monitoring the changes in the levels of tumor markers such as CEA,CA199 and CA724 is conducive to early diagnosis and evaluation of the occurrence of some solid tumors.AIM To investigate the expression of CEA,CA199 and CA724 in GC and their correlation with clinical features,hoping to provide more effective markers for the early preventive diagnosis of GC.METHODS Of 87 patients with GC admitted to our hospital from September 2020 to December 2021 were included in the GC group,and another 80 healthy people who came to our hospital for physical examination with normal results during the same period were selected as the control group.The serum CEA,CA199,and CA724 levels were compared between the two groups,and the serum CEA,CA199,and CA724 levels were compared in patients with GC at different TNM stages,and the differences in the positive rates of CEA,CA199,and CA724 alone and in combination in detecting TNM stages of GC and GC were compared.In addition,the relationship between the levels of tumor markers CEA,CA199 and CA724 and the clinicopathological characteristics of GC patients was also analyzed.The relationship between the serum levels of CEA,CA199 and CA724 and the survival period of GC patients was analyzed by Pearson.RESULTS The serum levels of CEA,CA199 and CA724 in GC group were significantly higher than those in control group(P<0.05).With the increase of TNM stage,the serum CEA,CA199 and CA724 expression levels in GC patients increased significantly,and the differences between groups were statistically significant(P<0.05).The positive rate of the CA724 single test was higher than that of CEA and CA199 single test(P<0.05).The positive rate of the three combined tests was 95.40%(83/87),which was higher than that of CEA,CA199 and CA724 single tests.The difference was statistically significant(P<0.05).The combined detection positive rates of CEA,CA199,and CA724 in stages I,II,III,and IV of GC were 89.66%,93.10%,98.85%,and 100.00%respectively,all of which were higher than the individual detection rates of CEA,CA199,and CA724.The differences were statistically significant(P<0.05).There was no significant difference in serum CEA,CA199 and CA724 levels between GC patients with different genders,smoking history and alcohol history(P>0.05).However,the serum CEA,CA199 and CA724 levels were significantly higher in GC patients aged≥45 years,TNM stage III-IV,with lymph node metastasis and tumor diameter≥5 cm than in GC patients aged<45 years,TNM stage I-II,without lymph node metastasis and tumor diameter<5 cm(P<0.05).CONCLUSION The expression levels of serum tumor markers CEA,CA199 and CA724 in patients with GC are high and rise with the increase of TNM stage.The levels of CEA,CA199 and CA724 are related to age,TNM stage,lymph node metastasis and tumor diameter.The combined detection of CEA,CA199 and CA724 is helpful to improve the diagnostic accuracy of GC with high clinical guidance value.
文摘BACKGROUND Carcinoembryonic antigen(CEA)is a broad-spectrum tumor marker for differential diagnosis,monitoring,and response assessment of a variety of malignancies.AIM To evaluate whether serum CEA could predict the prognosis in patients with colorectal cancer liver metastasis(CRCLM)before and after liver resection(LR).METHODS PubMed,Embase,Cochrane,and Web of Science were systematically searched to retrieve literature,with a search cut-off date of February 27,2023.Articles were strictly screened for inclusion according to pre-specified inclusion and exclusion criteria.Data were pooled and analyzed using Stata 16.0.RESULTS This meta-analysis included 36 studies involving a total of 11143 CRCLM patients.The results showed that a high pre-LR serum CEA level was correlated with poor overall survival(OS)[hazard ratio(HR)=1.61,95%confidence interval(CI):1.49-1.75,P<0.001]and recurrence-free survival(HR=1.27,95%CI:1.11-1.45,P<0.001)in CRCLM patients.A high post-LR serum CEA level predicted poor OS(HR=2.66,95%CI:2.10-3.38,P<0.001).A comparison by treatment modality,analysis modality,patient source,and cutoff-value showed that overall,high preoperative and postoperative serum CEA levels remained correlated with a poor prognosis.CONCLUSION This study concluded that high pre-LR and post-LR serum CEA levels were significantly correlated with a poor prognosis in CRCLM patients.
文摘BACKGROUND Preoperative chemoradiotherapy(CRT)is a standard treatment modality for locally advanced rectal cancer.However,CRT alone cannot improve overall survival.Approximately 20%of patients with CRT-resistant tumors show disease progression.Therefore,predictive factors for treatment response are needed to identify patients who will benefit from CRT.We theorized that the prognosis may vary if patients are classified according to pre-to post-CRT changes in carcinoembryonic antigen(CEA)levels.AIM To identify patients with locally advanced rectal cancer for preoperative chemoradiotherapy based on carcinoembryonic antigen levels.METHODS We retrospectively included locally advanced rectal cancer patients who underwent preoperative CRT and curative resection between 2011 and 2017.Patients were assigned to groups A,B,and C based on pre-and post-CRT serum CEA levels:Both>5;pre>5 and post≤5;and both≤5 ng/mL,respectively.We compared the response to CRT based on changes in serum CEA levels.Receiver operating characteristic curve analysis was performed to determine optimal cutoff for neutrophil–lymphocyte ratio and platelet–lymphocyte ratio.Multivariate logistic regression analysis was used to evaluate the prognostic factors for pathologic complete response(pCR)/good response.RESULTS The cohort comprised 145 patients;of them,27,43,and 65 belonged to groups A,B,and C,respectively,according to changes in serum CEA levels before and after CRT.Pre-(P<0.001)and post-CRT(P<0.001)CEA levels and the ratio of downstaging(P=0.013)were higher in Groups B and C than in Group A.The ratio of pathologic tumor regression grade 0/1 significantly differed among the groups(P=0.003).Group C had the highest number of patients showing pCR(P<0.001).Most patients with pCR showed pre-and post-CRT CEA levels<5 ng/mL(P<0.001,P=0.008).Pre-and post-CRT CEA levels were important risk factors for pCR(OR=18.71;95%CI:4.62–129.51,P<0.001)and good response(OR=5.07;95%CI:1.92–14.83,P=0.002),respectively.Pre-CRT neutrophil–lymphocyte ratio and post-CRT T≥3 stage were also prognostic factors for pCR or good response.CONCLUSION Pre-and post-CRT CEA levels,as well as change in CEA levels,were prognostic markers for treatment response to CRT and may facilitate treatment individualization for rectal cancer.
基金Supported by Foundation for Research Support of the State of Sao Paulo
文摘AIM: To evaluate the serum levels of cytokeratins and carcinoembryonic antigen (CEA) in diagnosis, staging and prognosis of patients with colorectal adenocarcinoma.METHODS: The sample consisted of 169 patients. One hundred blood donors formed the control group. Radical surgery was performed on 120 patients, with an average follow-up duration of 22.3 mo. Relapses occurred in 23individuals after an average of 18.09 mo. CEA was assayed via the Delfia(R) method with a limit of 5 ng/mL. Cytokeratins were assayed via the LIA-mat(R) TPA-M Prolifigen(R) method with a limit of 72 U/L.RESULTS: In the diagnosis of patients with colorectal adenocarcinoma, CEA showed a sensitivity of 56%, a specificity of 95%, a positive predictive value of 94%, a negative predictive value of 50% and an accuracy of 76.8%.TPA-M had a sensitivity of 70%, a specificity of 96%, a positive predictive value of 97%, a negative predictive value of 66% and an accuracy of 93.6%. The elevation of one of the markers was shown to have a sensitivity of 76.9%, a specificity of 91%, a positive predictive value of 93.5%, a negative predictive value of 70% and an accuracy of 83.6%.There was no variation in the levels of the markers according to the degree of cell differentiation while there was an elevation in their concentrations in accordance with the increase in neoplastic dissemination. There was a statistically significant difference between the patients with stage Ⅳ lesions and those with stages Ⅰ, Ⅱ and Ⅲ tumors.With regard to CEA, the averagelevel was 14.2 ng/mL in patients with stage Ⅰ lesions, 8.5 ng/mL in patients with stage Ⅱ lesions, 8.0 ng/mL in patients with stage Ⅲ lesions and 87.7 ng/mL in patients with stage Ⅳ lesions. In relation to TPA-M, the levels were 153.1 U/L in patients with stage Ⅰtumors, 106.5 U/L in patients with stage Ⅱ tumors, 136.3 U/L in patients with stage Ⅲ tumors and 464.3 U/L in patients with stage Ⅳ tumors. There was a statistical difference in patients with a high CEA level in relation to a shorter survival(P＜0.05). However, there was no correlation between patients with high TPA-M levels and prognostic indices of patients undergoing radical surgery.CONCLUSION: Cytokeratins demonstrate a greater sensitivity than CEA in the diagnosis of colorectal adenocarcinoma.There is an increase in the sensitivity of the markers with tumor dissemination. Cytokeratins cannot identify the worse prognosis in patients undergoing radical surgery.Cytokeratins constitute an advance in the direction of a perfect tumor marker in the treatment of patients with colorectal cancer.
基金Supported by the National Basic Research Program of China(973Program)(No.2015CB554001,JW)the National Natural Science Foundation of China(No.81972245,YL+6 种基金 No.81902877,HY)the Natural Science Fund for Distinguished Young Scholars of Guangdong Province(No.2016A030306002,YL)the Tip-top Scientific and Technical Innovative Youth Talents of Guangdong special support program(No.2015TQ01R454,YL)the Project 5010 of Clinical Medical Research of Sun Yat-sen University-5010Cultivation Foundation(No.2018026,YL)the Natural Science Foundation of Guangdong Province(No.2016A030310222,HY No.2018A0303130303,HY)the Program of Introducing Talents of Discipline to Universities,and National Key Clinical Discipline(2012)
文摘BACKGROUND Carcinoembryonic antigen(CEA)is a commonly used biomarker in colorectal cancer.However,controversy exists regarding the insufficient prognostic value of preoperative serum CEA alone in rectal cancer.Here,we combined preoperative serum CEA and the maximum tumor diameter to correct the CEA level,which may better reflect the malignancy of rectal cancer.AIM To assess the prognostic impact of preoperative CEA/tumor size in rectal cancer.METHODS We retrospectively reviewed 696 stage I to III rectal cancer patients who underwent curative tumor resection from 2007 to 2012.These patients were randomly divided into two cohorts for cross-validation:training cohort and validation cohort.The training cohort was used to generate an optimal cutoff point and the validation cohort was used to further validate the model.Maximally selected rank statistics were used to identify the optimum cutoff for CEA/tumor size.The Kaplan-Meier method and log-rank test were used to plot the survival curve and to compare the survival data.Univariate and multivariate Cox regression analyses were used to determine the prognostic value of CEA/tumor size.The primary and secondary outcomes were overall survival(OS)and disease-free survival(DFS),respectively.RESULTS In all,556 patients who satisfied both the inclusion and exclusion criteria were included and randomly divided into the training cohort(2/3 of 556,n=371)and the validation cohort(1/3 of 556,n=185).The cutoff was 2.429 ng/mL per cm.Comparison of the baseline data showed that high CEA/tumor size was correlated with older age,high TNM stage,the presence of perineural invasion,high CEA,and high carbohydrate antigen 19-9(CA 19-9).Kaplan-Meier curves showed a manifest reduction in 5-year OS(training cohort:56.7%vs 81.1%,P<0.001;validation cohort:58.8%vs 85.6%,P<0.001)and DFS(training cohort:52.5%vs 71.9%,P=0.02;validation cohort:50.3%vs 79.3%,P=0.002)in the high CEA/tumor size group compared with the low CEA/tumor size group.Univariate and multivariate analyses identified CEA/tumor size as an independent prognostic factor for OS(training cohort:hazard ratio(HR)=2.18,95%confidence interval(CI):1.28-3.73,P=0.004;validation cohort:HR=4.83,95%CI:2.21-10.52,P<0.001)as well as DFS(training cohort:HR=1.47,95%CI:0.93-2.33,P=0.096;validation cohort:HR=2.61,95%CI:1.38-4.95,P=0.003).CONCLUSION Preoperative CEA/tumor size is an independent prognostic factor for patients with stage I-III rectal cancer.Higher CEA/tumor size is associated with worse OS and DFS.
基金Supported by Changhai Hospital 1255 Project Fund,No.CH125542500
文摘AIM:To identify the predictors of distant metastasis in pathologically T1(pT1)colorectal cancer(CRC)after radical resection. METHODS:Variables including age,gender,preoperative carcinoembryonic antibody(CEA)level,tumor location,tumor size,lymph node status,and histological grade were recorded.Patients with and without metastasis were compared with regard to age,gender,CEA level and pathologic tumor characteristics using the independent t test orχ 2 test,as appropriate.Risk factors were determined by logistic regression analysis. RESULTS:Metastasis occurred in 6(3.8%)of the 159 patients during a median follow-up of 67.0(46.5%) mo.The rates of distant metastasis in patients with pT1 cancer of the colon and rectum were 6.7%and 2.9%, respectively(P<0.001).The rates of distant metastasis between male and female patients with T1 CRC were 6.25%and 1.27%,respectively(P<0.001).The most frequent site of distant metastasis was the liver. Age(P=0.522),gender(P=0.980),tumor location(P =0.330),tumor size(P=0.786),histological grade(P =0.509),and high serum CEA level(P=0.262)were not prognostic factors for lymph node metastasis.Univariate analysis revealed that age(P=0.231),gender(P =0.137),tumor location(P=0.386),and tumor size (P=0.514)were not risk factors for distant metastasis after radical resection for T1 colorectal cancer.Postoperative metastasis was only significantly correlated with high preoperative serum CEA level(P=0.001).Using multivariate logistic regression analysis,high preoperative serum CEA level(P=0.004;odds ratio 15.341; 95%CI 2.371-99.275)was an independent predictor for postoperative distant metastasis. CONCLUSION:The preoperative increased serum CEA level is a predictive risk factor for distant metastasis in CRC patients after radical resection.Adjuvant chemotherapy may be necessary in such patients,even if they have pT1 colorectal cancer.
基金Supported by Domestic Support from Young and Middle-aged key personnel Training program for provincial Health planning Students,No.2017-ZQN-18provincial Youth Health Science Research project,No.2014-2-8 and No.2017-1-13National key Clinical Specialty Construction project,No.2013-2016
文摘AIM To assess whether elevated serum carcinoembryonic antigen(CEA) is in the inferior prognosis for pathological lymph node-negative(p N_0) gastric cancer(GC) patients who underwent D_2 gastrectomy.METHODS About 469 p N0 GC patients,who received D^2 radical gastrectomy were retrospectively analyzed. The X-tile plots cut-off point for CEA were 30.02 ng/m L using minimum P-value from log-rank χ~2 statistics,and p N_0 GC patients were assigned to two groups: those more than 30.02 ng/m L(n = 48;CEA-high group) and those less than 30.02 ng/m L(n = 421;CEA-low group). Clinicopathologic characteristics were compared usingPearson's χ2 or Fisher's exact tests,and survival curves were so manufactured using the Kaplan-Meier method. Univariate and multivariate analysis were carried out using the logistic regression method.RESULTS The percentage of vessel carcinoma embolus(31.35% vs 17.1%) and advanced GC(T_(2-4b))(81.25% vs 65.32%) were higher in CEA-high group than CEA-low group. The CEA-positive patients had a significantly poorer prognosis than the CEA-nagetive patients in terms of overall survival(57.74% vs 90.69%,P < 0.05),and no different was found between subgroup of T category,differentiation,nerve invasion,and vessel carcinoma embolus(all P > 0.05). Multivariate survival analysis showed that CEA(OR = 4.924),and T category(OR = 2.214) were significant prognostic factors for stage p N0 GC(all P < 0.05). Besides,only T category(OR = 1.962) was an independent hazard factor in the CEA-high group(P < 0.05).CONCLUSION Those pretreatment serum CEA levels over 30.02 ng/m L on behalf of worse characteristics and unfavourable tumor behavior,and a poor prognosis for a nearly doubled risk of mortality in GC patients.
文摘AIM:To evaluate the value of positron emission tomography(PET)/computerized tomography(CT)in surveillance of colorectal cancer(CRC)patients with different carcinoembryonic antigen(CEA)concentrations.METHODS:One hundred and six postoperative CRC patients who had suspected recurrence or metastasis and received fluorodeoxyglucose(FDG)PET/CT within one week were included in this study.The final diagnosis was confirmed by histological examination or clinicalfollow-up over at least six months.RESULTS:The sensitivity,specificity,and accuracy of FDG PET/CT were 95.2%,82.6%,and 92.5%,and94.8%,81.4%and 92.8%,respectively,in the caseand lesion-based analyses.The sensitivity and accuracy of FDG PET/CT significantly differed from CT in both analyses(χ2=8.186,P=0.004;χ2=6.201,P=0.013;χ2=13.445,P=0.000;χ2=11.194,P=0.001).In the lesion-based analysis,the sensitivity,specificity,and accuracy of FDG PET/CT in the abnormal CEA group were97.8%,82.6%,and 95.6%,compared with 81.3%,80%,and 80.6%for patients with normal CEA levels.In case-based analysis,the sensitivity,specificity,and accuracy of FDG PET/CT were 97.2%,77.8%,and 95%in abnormal CEA group.Only in lesion-based analysis,the sensitivity and accuracy of FDG PET/CT in the abnormal CEA group were significantly superior to those in the normal CEA group(χ2=6.432,P=0.011;χ2=7.837,P=0.005).FDG PET/CT changed the management in 45.8%of patients with positive scans.CONCLUSION:FDG PET/CT showed superior diagnostic value and is an advisable option in surveillance of postoperative CRC patients with a vague diagnosis.
基金Supported by The Khon Kaen University Publication Clinic,Research
文摘AIM: To evaluate outcomes in resectable cholangiocarcinoma patients and to determine prognostic factors. METHODS: A retrospective study was conducted among newly-diagnosed cholangiocarcinoma patients from January 2009 to December 2011 who underwent curative resection in Srinakarind Hospital (a 1000-bed university hospital). Two hundred and sixty-three cholangiocarcinoma patients with good performance were enrolled. These patients had pathological reports with clear margins or microscopic margins. Prognostic factors which included clinical factors, serum liver function test as well as serum tumor makers at presentation,tumor data, and receiving adjuvant chemotherapy were determined by uniand multivariate analysis. RESULTS: The median overall survival time was 17 mo (95%CI: 13.2-20.7); and 1-, 2-, and 3year survival rates were 65.5%, 45.2% and 35.4%. Serum albumin levels, serum carcinoembryonic antigen (CEA) levels, staging classifications by American Joint Committee on cancer, pathological tumor staging, lymph node metastases, tumor grading, surgical margin status, and if adjuvant chemotherapy was administered, were shown to be significant prognostic factors of resectable cholangiocarcinoma by univariate analysis. Multivariate analysis, however, established that only abnormal serum CEA [hazard ratio (HR) 1.68; P = 0.027] and lymph node metastases (HR 2.27; P = 0.007) were significantly associated with a decrease in overall survival, while adjuvant chemotherapy (HR 0.71; P = 0.067) and surgical margin negative (HR 0.72; P = 0.094) tended to improve survival time. CONCLUSION: Serum CEA and lymph node metastases which were associated with advanced stage tumors become strong negative prognostic factors in cholangiocarcinoma.
文摘AIM: To investigate the impact of RAS and BRAF mutations on the pattern of metastatic disease and carcinoembryonic antigen(CEA) production.METHODS: In this retrospective study, we investigated the impact of RAS and BRAF mutational status on pattern of metastatic disease and CEA production. Only patients presenting with a newly diagnosed metastatic colorectal cancer(CRC) were included. Patients' characteristics, primary tumor location, site of metastatic disease and CEA at presentation were compared between those with and without RAS and BRAF mutations.RESULTS: Among 174 patients, mutations in KRAS, NRAS and BRAF were detected in 47%, 3% and 6% respectively. RAS mutations(KRAS and NRAS) were more likely to be found in African American patients(87% vs 13%; P value = 0.0158). RAS mutations were associated with a higher likelihood of a normal CEA(< 5 ng/mL) at presentation. BRAF mutations were more likely to occur in females. We were not able to confirm any association between mutational status and site of metastatic disease at initial diagnosis.CONCLUSION: No association was found between RAS and BRAF mutations and sites of metastatic disease at the time of initial diagnosis in our cohort. Patients with RAS mutations were more likely to present with CEA levels < 5 ng/mL. These findings may have clinical implications on surveillance strategies for RAS mutant patients with earlier stages of CRC.
文摘Pancreatic cystic lesions(PCLs) have been increasingly recognized in clinical practice. Although inflammatory cysts(pseudocysts) are the most common PCLs detected by cross-sectional imaging modalities in symptomatic patients in a setting of acute or chronic pancreatitis, incidental pancreatic cysts with no symptoms or history of pancreatitis are usually neoplastic cysts. For these lesions,it is imperative to identify mucinous cysts(intraductal papillary mucinous neoplasms and mucinous cystic neoplasms) due to the risk of their progression to malignancy. However, no single imaging modality alone is sufficient for a definitive diagnosis of all PCLs. The cyst fluid obtained by endoscopic ultrasound-guided fine needle aspiration provides additional information for the differential diagnosis of PCLs. Current recommendations suggest sending cyst fluid for cytology evaluation and measurement of carcinoembryonic antigen(CEA) levels. Unfortunately, the sensitivity of cytology is greatly limited, and cyst fluid CEA has demonstrated insufficient accuracy as a predictor of mucinous cysts. More recently, cyst fluid glucose has emerged as an alternative to CEA for distinguishing between mucinous and nonmucinous lesions. Herein, the clinical utility of cyst fluid glucose and CEA for the differential diagnosis of PCLs was evaluated.
文摘Objective: To identify prognostic factors in patients with locally advanced cervical cancer treated with concurrent chemoradiotherapy (CCRT). Methods and Materials: We analyzed 76 patients with FIGO stage IB2 - IVb cervical cancer treated with CCRT between 2001 and 2006 at the Nagoya University Hospital. Patients with an advanced cervical cancer treated with CCRT. Overall survival (OS) and Progression-free survival (PFS) rates were estimated using the Kaplan-Meier method. The log-rank test was used to test differences in survival. Fisher's exact test was employed for univariate analysis. The Cox proportional hazard model was used for multivariate analysis. Results: The median age was 52, and the median follow-up period was 36 months. The 5 - year OS and PFS rates of all patients were 88.2% and 72.4%, respectively. Twenty-one of the 76 patients were diagnosed with recurrence. A higher serum CEA before CCRT was an independent predictive factor for a poor prognosis on multivariate analysis. Conclusions: A high level of serum CEA was a predictive factor for a poor prognosis. New strategies should be considered to control disease in this group of patients.
基金Supported by grants from the Medicine and Health Care Science and Technology Development Plan Projects Foundation of Shandong Province(No.2014WS0282,2014WSA11003)Application Technology Research and Development Project Foundation in Rizhao City(No.2014SZSH02)+1 种基金Science and technology innovation project of medical workers in Shandong Province(No.201515)the Scientific Research Projects of Jining Medical College(No.JY2013KJ051)
文摘Objective This study aimed to evaluate serum and nipple discharge levels of carcinoembryonic antigen(CEA) and cancer antigen 153(CA153) and tissue cyclooxygenase-2(COX-2) expression in breast cancer cases and associations of these proteins with breast cancer metastasis.Methods The immunohistochemical Ultra Sensitive^(TM) S-P method was used to detect COX-2 expression in 77 cases of invasive breast carcinoma. Of these cases, 52 exhibited CEA and CA153 in both serum and nipple discharge(electrochemiluminescence method), and associations of these biomarkers with breast cancer prognosis were studied. Sixty cases of benign breast lesion were selected as a control group. Overall survival of breast carcinoma patients was evaluated. COX-2 expression was evaluated relative to clinicopathological features and CEA and CA153 levels, and its role in invasiveness was investigated.Results Among cases of invasive breast cancer, 72.7%(56/77) were COX-2 immunopositive, compared to 16.7% of benign lesions(χ2 = 66.745, P = 0.000) percentage of positive cells. COX-2 overexpression in breast cancer correlated positively with histological grade(II vs III; χ2 = 4.064, P = 0.043), lymph node metastasis(χ2 = 9.135, P = 0.003), and distant metastasis(χ2 = 8.021, P = 0.003). However, COX-2 expression did not correlate with age(≤ 50 vs 50 years) or tumor size(≤ 5 vs > 5 cm)(χ2 = 0.081, P = 0.776 and χ2 = 3.702, P = 0.054, respectively). Among breast cancer patients, COX-2 overexpression in tumors also correlated with shorter overall survival(P < 0.05). In brief, increased COX-2 expression correlates with worse prognosis and shorter overall survival. Malignant lesions were associated with significantly higher serum and nipple discharge levels of biomarkers, relative to benign lesions(P < 0.05). These biomarkers were present at significantly higher levels in nipple discharge than in serum(P < 0.05). Furthermore, significantly higher nipple discharge levels of CEA and CA153 were observed in COX-2-positive breast carcinoma patients, compared to COX-2-negative patients(P <0.05). Shorter overall survival in cancer patients group related to COX-2 overexpression in tumors(P < 0.05).Conclusion The study suggests that COX-2 overexpression correlates with poor clinicopathological parameters in breast cancers and might be an important biological marker of invasion and metastasis. The findings of the present study suggest that combined detection of COX-2 tissue expression and CEA and CA153 in serum and nipple discharge could facilitate clinical monitoring and diagnosis of metastasis in patients with breast cancer.
文摘BACKGROUND Carcinoembryonic antigen(CEA)is an important serum tumour marker with a substantial role in diagnosis and monitoring of various solid tumours.About 36%-70%of breast cancers have elevated serum CEA.And the available studies show discrepancy in addressing the prognostic significance of CEA in advanced breast cancer.AIM To estimate the serum CEA level in our metastatic breast cancer patients and correlate it with response to treatment and clinical outcome.METHODS This was a prospective clinical study conducted on 50 metastatic breast cancer patients treated at breast clinic,with newly diagnosed metastatic breast cancer planned for palliative chemotherapy,targeted therapy,and hormonal treatment.We estimated the proportion of patients with elevated serum CEA level at baseline and after palliative treatment and also studied the association of serum CEA levels with known prognostic factors.The response to treatment was correlated with the serum CEA levels in the context of responders and nonresponders.RESULTS The median pre-treatment and post-treatment CEA levels were 7.9(1.8-40.7)ng/mL and 4.39(1.4-12.15)ng/mL,respectively,in the whole study population(P=0.032).No statistically significant difference was seen in baseline serum CEA between responders and non-responders.Even in the luminal group,pretreatment serum CEA was not a predictor of response,but post-treatment CEA was a significant predictor of tumour progression.In patients with liver and lung metastases,post-treatment CEA level difference was not statistically significant in both responders and non-responders though the values were higher in nonresponders.Among those with bone metastases,69.5%had elevated post-treatment serum CEA,and only 37.5%had elevated serum CEA in those with no bone metastases.CONCLUSION Elevated post-treatment serum CEA levels are associated with disease progression and poor response to therapy.Persistently elevated post-treatment serum CEA levels are significantly associated with bone metastases.Elevated serum CEA and hormonal status are significant predictors of treatment response.
文摘Aim: The objective of this study was to investigate the prognostic value of serum carcinoembryonic antigen (CEA) level in colorectal cancer patients with liver metastases. The serum CEA level was recorded at the point of metastasis diagnosis, differing from the majority of literature looking at preoperative metastasectomy CEA level. Methods: From January 2010 to December 2014, 138 patients with a diagnosis of colorectal cancer and liver metastases were included in the study—population from Buenos Aires, Argentina. Patients with both resectable and unresectable liver metastases were followed up over a 4-year period. Kaplan Meier survival analysis was used to produce survival curves that were compared by log-rank test. Results: The overall survival for all patients studied with a CEA < 100 ng/ml was significantly longer compared to patients with CEA ≥ 100 ng/mL (p < 0.001). The 1-, 2-, and 3-year overall survival rates for the whole cohort were 73.6, 56.6 and 53.8% respectively. For patients with unresectable metastases, a low CEA level (<100 ng/mL) was also associated with the increased overall survival (p = 0.036). Conclusions: In our patient cohort, this study indicated that a low CEA level (<100 ng/mL) measured at metastasis diagnosis was a good prognostic indicator for improving survival in patients with colorectal liver metastases. These findings highlight the importance of measuring serum CEA levels in this group of patients at the time of liver metastasis diagnosis.
文摘The long-term success of gene therapy for cancer relies heavily on the deveiopment of effective targeting systems. We investigate the possibility of targeted gene therapy using promoter of carcinoembryonic antigen (CEA) gene. By using luciferase reporter gene, we found that CEA promoter exhibit 16 times high activity in CEA-producing lung cancer cells, A549 than in nonproducing cells, Hela. We also constructed a recombinant expression plasmid pCEATK, in which CEA promoter drives the effector gene, thymidine ki-nase gene of Herpes Simplex Virus (HSVTK). A549 cells transfected with pCEATK became 865 times more sensitive to ganclclovir (GCV) than the control cells. However, Hela cells transfected with this plasmid re-mained resistant to GCV. These data indicate the potential for targeted gene therapy using the CEA promoter against CEA-producing tumor cells, suck as lung cancer cells.
基金supported by grants from the National Natural Science Foundation of China(No.81873473 and No.91939110)Academic Promotion Program of Shandong First Medical University(No.2019QL014)Shandong Taishan Scholarship(Ju Liu).
文摘Objective:Lymphatic endothelial cell(LEC)proliferation is essential for lymphangiogenesis.Hypoxia induces lymphangiogenesis,but it directly inhibits LEC proliferation and the underlying mechanisms have not been fully understood.The aim of this study was to investigate the role of carcinoembryonic antigen-related cell adhesion molecule 1(CEACAM1)in hypoxia-repressed LEC proliferation.Methods:Human dermal lymphatic endothelial cells(HDLECs)were cultured under normoxic or hypoxic conditions,and cell proliferation was determined using MTT or CCK-8 assays.CEACAM1 expression was silenced by siRNA transfection.Activation of mitogen-activated protein kinases(MAPKs)was examined by Western blotting and blocked by specific inhibitors.Results:Under hypoxia,HDLECs proliferation was suppressed and CEACAM1 expression was downregulated.Silence of CEACAM1 in normoxia inhibited HDLECs proliferation and did not further decrease proliferation in HDLECs in response to hypoxia,suggesting that CEACAM1 may mediate hypoxia-induced inhibition of HDLECs proliferation.In addition,silence of CEACAM1 increased phosphorylation of MAPK molecules:extracellular signal-regulated kinase(ERK),p38 MAPK and Jun N-terminal kinase(JNK)in HDLECs.However,only inhibition of the JNK pathway rescued the reduction of HDLEC proliferation induced by CEACAM1 silence.Conclusion:Our results suggested that hypoxia downregulates CEACAM1 expression by activation of the JNK pathway,leading to inhibition of HDLEC proliferation.These findings may help to understand the mechanisms of LEC-specific response to hypoxia and develop novel therapies for pathological lymphangiogenesis.
基金supported by a grant from The National "863" Project of China(No.2001AA215371)
文摘Objective: To study the preparation and characterization of monoclonal antibody (McAb) against carcinoembryonic antigen (CEA). Methods: CEA antigen was extracted from metastasized liver of patients with colorectal cancer and used for the preparation of McAb against CEA by hybridoma technique. Immunoreactivity of McAb to CEA antigen was evaluated using ELISA. Mouse ascites was purified by two steps, high performance liquid chromatography (HPLC) using protein A and high performance hydroxylapatite (HPHT). Normal adult tissues and tumor specimen were used for immunohistochemical evaluation of the McAb. Isotope 99mTc labeled CEA McAb was used for biodistribution in tumor-bearing mouse. Results: Purified CEA antigen was a glycoprotein of 180 kD. Anti-CEA McAb affinity constant was 7.4x109/M. The McAb showed positive staining in 54-88% of colorectal cancer, gastric cancer and lung cancer, while negative for normal tissues. 24 hours after injection of 99mTc labeled McAb, tumor ID%/g was higher than 15% and tumor/blood, tumor/kidney and tumor/liver were 1.82, 1.51 and 2.92 respectively. T/NT ratios of other viscera were over 3.0. Conclusion: Purified CEA antigen had very good immunogenicity. The anti-CEA McAb was highly specific. 99mTc labeled McAb was stabled both in vivo and in vitro. In vivo distribution result was satisfactory. McAb CL58 may be useful for RII and RIGS.
文摘Objective: To investigate the relationship betwhen production of carcinoembryonic antigen (CEA) in thehuman cells of different tissues and scquence variation of t CEA promoter in the cellular genomes. and evaluate po-tential application of the ets active scqucnce of CEA gene in colorectal carcinoma tissie-specific gene therapy.Methods: Nested-polymerase chain reaction (PCR) was employed to amplify the CEA promoter sequences fromthe genome of human colorectal carcinoma. normal adjacent colonic mucosa tissues. normal blood cells. placentatissues and some established cell lines of human origin. PCR-Southern bloting assay was utilized to define the reliability of the amplified sequences. The scquence variations were evaluated by means of PCR-single stranded conformation polymorphism (PCR-SSCP) and DNA sequencing. Binding effect of the amplified fragment was examinedby Band-Shift assay. Results: No scqucnce variation was found between-135bp and+69bp from the transcription-al initiation site. which was considered to be a core region of CEA promoter. There was no correlativity betweenproduction levels of CEA and sequence variations of CEA gene promoter core region. The fragment amplified either from normal tissues or from colorectal carcinoma tissues could equally bind with the nuclear extract from Lo-Vo cells. Conclusion: Differential level of CEA gene transcription in the colorectal carcinoma cells. as comparedwith normal tissues, was proved not to be related to the sequence variation of CEA promoter core region. CEApromoters, either from normal cellular genome or neoplasm cellular genome. were found suitable for colorectalcarcinoma tissue-specific gene therapy.
