AIM To investigate the relationship between autophagy and perineural invasion(PNI), clinical features, and prognosis in patients with pancreatic cancer. METHODS Clinical and pathological data were retrospectively coll...AIM To investigate the relationship between autophagy and perineural invasion(PNI), clinical features, and prognosis in patients with pancreatic cancer. METHODS Clinical and pathological data were retrospectively collected from 109 patients with pancreatic ductal adenocarcinoma who underwent radical resection at the First Affiliated Hospital of Zhengzhou University from January 2011 to August 2016. Expression levels of the autophagy-related protein microtubuleassociated protein 1 A/1 B-light chain 3(LC3) and PNI marker ubiquitin carboxy-terminal hydrolase(UCH) in pancreatic cancer tissues were detected by immunohistochemistry. The correlations among LC3 expression, PNI, and clinical pathological features in pancreatic cancer were analyzed. The patients were followed for further survival analysis. RESULTS In 109 cases of pancreatic cancer, 68.8%(75/109) had evidence of PNI and 61.5%(67/109) had high LC3 expression. PNI was associated with lymph node metastasis, pancreatitis, and CA19-9 levels(P < 0.05). LC3 expression was related to lymph node metastasis(P < 0.05) and was positively correlated with neural invasion(P < 0.05, r = 0.227). Multivariate logistic regression analysis indicated that LC3 expression, lymph node metastasis, pancreatitis, and CA19-9 level were factors that influenced neural invasion, whereas only neural invasion itself was an independent factor for high LC3 expression. Univariate analysis showed that LC3 expression, neural invasion, and CA19-9 level were related to the overall survival of pancreatic cancer patients(P < 0.05). Multivariate COX regression analysis indicated that PNI and LC3 expression were independent risk factors for poor prognosis in pancreatic cancer(P < 0.05). CONCLUSION PNI in patients with pancreatic cancer is positively related to autophagy. Neural invasion and LC3 expression are independent risk factors for pancreatic cancer with a poor prognosis.展开更多
BACKGROUND Breast cancer is the most common malignancy in women all around the world.According to the latest statistics in 2018,there were more than 2.08 million new breast cancer cases all around the world and more t...BACKGROUND Breast cancer is the most common malignancy in women all around the world.According to the latest statistics in 2018,there were more than 2.08 million new breast cancer cases all around the world and more than 620000 deaths;the proportion of breast cancer deaths in women with cancer is 15%.By studying age,clinicopathological characteristics and molecular classification,age at menarche,age at birth,number of births,number of miscarriages,lactation time,surgical history of benign breast lesions,history of gynecological diseases,and other factors,we retrospectively summarized and compared the disease history of patients with primary breast cancer and patients with benign thyroid tumors admitted to our hospital in the past 10 years to explore the clinicopathological characteristics and risk factors for primary breast cancer.AIM To investigate the clinical and pathological features and risk factors for primary breast cancer treated at our center in order to provide a reference for the prevention and treatment of breast cancer in the Zhuhai-Macao region.METHODS Through a retrospective case-control study,149 patients with primary breast cancer diagnosed and treated at Zhuhai Hospital of Guangdong Provincial Hospital of Traditional Chinese Medicine from January 2013 to March 2020 were included as a case group,and 165 patients with benign breast tumors diagnosed and treated from January 2019 to March 2020 were included as a control group.The data collected included age,age at menarche,age at first birth,number of births,number of miscarriages,lactation time,history of surgery for benign breast lesions,history of familial malignant tumors,history of gynecological diseases,history of thyroid diseases,and the tumor characteristics of the patients in the case group including pathological diagnosis,pathological type,tumor size,lymph node metastasis,distant metastasis,stage,and molecular classification,among others.In the case group,the chi-square test was used to analyze the clinical and pathological features of patients in three age groups(<40,40-59,and≥60 years).A multifactor logistic regression analysis was used to analyze correlations between the two groups.RESULTS Among 149 patients with primary breast cancer,the average age was 48.20±12.06 years,and the proportion of patients at 40-59 years old was the highest,accounting for 61.8%of cases.The molecular type was mainly luminal B type,accounting for 69.2%of cases,and at the time of diagnosis,the tumor stage was mainly stage I/II,accounting for 62.4%of cases.There were no statistically significant differences in the distributions of tumor location,pathological type,tumor size,lymph node metastasis,stage,or molecular classification among the three age groups(<40,40-59,and≥60 years)(P≥0.05).The differences in the distribution of distant metastasis among the three age groups(<40,40-59,and≥60 years)were statistically significant(P<0.01).The differences in lactation time,history of familial malignant tumors,history of gynecological diseases,and history of thyroid diseases between the two groups were not statistically significant(P≥0.05).The differences in age at disease diagnosis,age at menarche,and history of surgery for benign breast lesions were statistically significant(P<0.01).The difference in age at first birth was also statistically significant(P<0.05).CONCLUSION The highest incidence of breast cancer in the Zhuhai-Macao region is present among women aged 40-59 years.There is a larger proportion of stage I/II patients,and the luminal B type is the most common molecular subtype.Distant metastasis occurs mainly in the≥60-year-old group at the first diagnosis;increased age,late age at menarche,and late age at first birth may be risk factors for primary breast cancer,and a history of surgery for benign breast lesions may be a protective factor for primary breast cancer.展开更多
BACKGROUND: Devic's neuromyelitis optica (DNMO) and multiple sclerosis in Asian populations have been considered to be the same disease. However, there is an increasing number of studies suggesting that DNMO and m...BACKGROUND: Devic's neuromyelitis optica (DNMO) and multiple sclerosis in Asian populations have been considered to be the same disease. However, there is an increasing number of studies suggesting that DNMO and multiple sclerosis are different diseases. OBJECTIVE: Little information is available regarding comparisons of DNMO patients between China and other countries, as well as clinical manifestations of Chinese patients with DNMO and multiple sclerosis. The present study performed a multicenter, pathological, retrospective analysis. DESIGN, TIME AND SETTING: A retrospective analysis of clinical data from seven patients with DNMO diagnosed between 1957 and 1998. PARTICIPANTS: Data from Chinese DNMO patients was provided by the Shanghai Second Medical University, Sun Yat-sen University of Medical Sciences and the First Affiliated Hospital of Harbin Medical University in China. METHODS: Clinical and pathological data from Chinese patients with DNMO were retrospectively analyzed. The clinical characteristics of DNMO were compared between Chinese and Caucasian patients. In addition, clinical and pathological differences between DNMO and multiple sclerosis Chinese patients were compared. MAIN OUTCOME MEASURES: Clinical and pathological features of Chinese patients with DNMO. RESULTS: All seven Chinese patients with DNMO exhibited abrupt onset of vision disturbance, with a disease course of 3 days to 9 years. DNMO recurred in two of the patients. Demyelinating lesions were observed in all patients, with necrotic lesions and gitter cells in five patients, collagenous hyperplasia in one patient, and perivascular inflammatory cell infiltration in six patients. Comparison between Chinese and Caucasian DNMO patients revealed no significant differences in age at onset, clinical onset, duration, or interval between optic neuritis and myelitis. Compared with Chinese multiple sclerosis patients, Chinese DNMO patients presented with fewer recurrences, higher occurrence of necrosis, perivascular inflammatory cell infiltration and gitter cells, and a lower occurrence of collagenous hyperplasia. CONCLUSION: There was no difference in DNMO clinical features between Chinese and Caucasian patients. However, the clinical and pathological features of DNMO were different compared with multiple sclerosis in Chinese patients. Results suggested that the characteristics of DNMO in Chinese patients were significantly different than multiple sclerosis.展开更多
BACKGROUND Endoscopy has rapidly developed in recent years and has enabled further investigation into the origin and features of intestinal tumors.The small size and concealed position of these tumors make it difficul...BACKGROUND Endoscopy has rapidly developed in recent years and has enabled further investigation into the origin and features of intestinal tumors.The small size and concealed position of these tumors make it difficult to distinguish them from nonneoplastic polyps and carcinoma in adenoma(CIA).The invasive depth and metastatic potential determine the operation regimen,which in turn affects the overall survival and distant prognosis.The previous studies have confirmed the malignant features and clinicopathological features of de novo colorectal cancer(CRC).AIM To provide assistance for diagnosis and treatment,but the lack of a summary of endoscopic features and assessment of risk factors that differ from the CIA prompted us to conduct this retrospective study.METHODS In total,167 patients with small-sized CRCs diagnosed by endoscopy were reviewed.The patients diagnosed as advanced CRCs and other malignant cancers or chronic diseases that could affect distant outcomes were excluded.After screening,63 cases were excluded,including 33 de novo and 30 CIA cases.Patient information,including their follow-up information,was obtained from an electronic His-system.The characteristics between two group and risk factors for invasion depth were analyzed with SPSS 25.0 software.RESULTS Nearly half of the de novo CRCs were smaller than 1 cm(n=16,48.5%)and the majority were located in the distal colon(n=26,78.8%).The IIc type was the most common macroscopic type of de novo CRC.In a Pearson analysis,the differential degree,Sano,JNET,and Kudo types,surrounding mucosa,and chicken skin mucosa(CSM)were correlated with the invasion depth(P<0.001).CSM was a significant risk factor for deep invasion and disturbed judgment of endoscopic ultrasound.A high degree of tumor budding and tumor-infiltrating lymphocytes are accompanied by malignancy.Finally,de novo CRCs have worse outcomes than CIA CRCs.CONCLUSION This is the first comprehensive study to analyze the features of de novo CRCs to distinguish them from nonneoplastic polyps.It is also the first study paying attention to CSM invasive depth measurement.This study emphasizes the high metastatic potential of de novo CRCs and highlights the need for more research on this tumor type.展开更多
BACKGROUND The clinicopathological features and prognosis of gastric signet ring cell carcinoma(GSRC)remain controversial,particularly with regard to sensitivity to postoperative adjuvant therapy.AIM To compare the pa...BACKGROUND The clinicopathological features and prognosis of gastric signet ring cell carcinoma(GSRC)remain controversial,particularly with regard to sensitivity to postoperative adjuvant therapy.AIM To compare the pathological features of GSRC with those of gastric adenocarcinoma of different degrees of differentiation and the differences in survival prognosis between the different disease processes.METHODS By screening gastric cancer patients from 2010 to 2015 in the database of Surveillance,Epidemiology and End Results,and collecting the clinicopathological and prognostic data of gastric cancer patients who underwent surgery from January 2014 to December 2016 in the Second Affiliated Hospital of Nanchang University,we analyzed the general pathological characteristics of GSRC by the chi-square test.Univariate and multivariate analyses were conducted to compare the factors affecting the survival and prognosis of early and advanced gastric adenocarcinoma.The Kaplan-Meier curves were plotted to reveal the survival difference between early and advanced GSRC and different differentiated types of gastric adenocarcinoma.The prognosis model of advanced GSRC was established with R software,and the area under curve(AUC)and C-index were used to assess the accuracy of the model.RESULTS Analysis of pathological features revealed that signet ring-cell carcinoma(SRC)was more frequently seen in younger(<60 years),female,and White patients compared to non-SRC patients.SRC was less commonly associated with early gastric cancer(EGC)(23.60%vs 39.10%),lower N0(38.61%vs 61.03%),and larger tumour sizes>5 cm(31.15%vs 27.10%)compared to the differentiated type,while the opposite was true compared to the undifferentiated type.Survival prognostic analysis found no significant difference in the prognosis of SRC patients among EGC patients.In contrast,among advanced gastric cancer(AGC)patients,the prognosis of SRC patients was correlated with age,race,tumour size,AJCC stage,T-stage,and postoperative adjuvant therapy.The predictive model showed that the 3-year AUC was 0.787,5-year AUC was 0.806,and C-index was 0.766.Compared to non-SRC patients,patients with SRC had a better prognosis in EGC[hazard ratio(HR):0.626,95%confidence interval(CI):0.427-0.919,P<0.05]and a worse prognosis in AGC(HR:1.139,95%CI:1.030-1.258,P<0.05).When non-SRC was divided into differentiated and undifferentiated types for comparison,it was found that in EGC,SRC had a better prognosis than differentiated and undifferentiated types,while there was no significant difference between differentiated and undifferentiated types.In AGC,there was no significant difference in prognosis between SRC and undifferentiated types,both of which were worse than differentiated types.A prognostic analysis of postoperative adjuvant therapy for SRC in patients with AGC revealed that adjuvant postoperative radiotherapy or chemotherapy significantly improved patient survival(34.6%and 36.2%vs 18.6%,P<0.05).CONCLUSION The prognosis of SRC is better than that of undifferentiated type,especially in EGC,and its prognosis is even better than that of differentiated type.SRC patients can benefit from early detection,surgical resection,and aggressive adjuvant therapy.展开更多
Objective:To investigate the effect of programmed death-ligand 1(PD-L1)gene polymorphism on pathological characteristics and clinical prognosis quality in patients with esophageal cancer.Methods:86 patients with esoph...Objective:To investigate the effect of programmed death-ligand 1(PD-L1)gene polymorphism on pathological characteristics and clinical prognosis quality in patients with esophageal cancer.Methods:86 patients with esophageal cancer treated in our hospital from January 2014 to January 2017 were selected as the observation group,and 100 healthy patients were selected as the control group during the same period.The single nucleotide polymorphisms of rs2890658,rs17718883,rs2297136 and rs4143185 at different sites were determined.And the impact of PD-L1 gene polymorphism on pathological features and prognosis of esophageal cancer were analyzed.Results:The observation group finally completed 84 cases,and the control group included 99 cases.There were differences between the observation group and the control group in the PD-L1 different genetic locus rs17718883,rs2890658,rs2297136(P<0.05).The PD-L1 locus rs17718883 was related to the pathological type and degree of differentiation of esophageal cancer,the difference was statistically significant(P<0.05),rs2890658 was related to the degree of differentiation of esophageal cancer,the difference was statistically significant(P<0.05).Log-rank test showed that the genotype of rs17718883 in patients with esophageal cancer was related to prognostic survival,and the difference was statistically significant(P<0.05).Cox proportional hazards model analysis showed that age,degree of differentiation,lymph node metastasis,and rs17718883 genotype were independent factors in the prognosis of patients with esophageal cancer,and the difference was statistically significant(P<0.05).Conclusion:The polymorphisms of rs17718883 and rs2890658 loci of PD-L1 gene have an impact on the clinicopathological characteristics of patients with esophageal cancer,and the polymorphisms of rs17718883 locus of PD-L1 gene have an impact on the clinical prognosis quality.展开更多
BACKGROUND Primary sclerosing cholangitis(PSC)associated inflammatory bowel disease(IBD)is a unique form of IBD(PSC-IBD)with distinct clinical and histologic features from ulcerative colitis(UC)and Crohn disease(CD).I...BACKGROUND Primary sclerosing cholangitis(PSC)associated inflammatory bowel disease(IBD)is a unique form of IBD(PSC-IBD)with distinct clinical and histologic features from ulcerative colitis(UC)and Crohn disease(CD).In patients with PSC and IBD,the severity of the two disease processes may depend on each other.AIM To study the histologic and clinical features of PSC patients with and without IBD.METHODS We assessed specimens from patients with UC(n=28),CD(n=10),PSC and UC(PSC-UC;n=26);PSC and CD(PSC-CD;n=6);and PSC and no IBD(PSC-no IBD;n=4)between years 1999-2013.PSC-IBD patients were matched to IBD patients without PSC by age and colitis duration.Clinical data including age,gender,age at IBD and PSC diagnoses,IBD duration,treatment,follow-up,orthotopic liver transplantation(OLT)were noted.RESULTS PSC-UC patients had more isolated right-sided disease(P=0.03),and less active inflammation in left colon,rectum(P=0.03 and P=0.0006),and overall(P=0.0005)compared to UC.They required less steroids(P=0.01)and fewer colectomies(P=0.03)than UC patients.The PSC-CD patients had more ileitis and less rectal involvement compared to PSC-UC and CD.No PSC-CD patients required OLT compared to 38%of PSC-UC(P=0.1).PSC-IBD(PSC-UC and PSCCD)patients with OLT had severe disease in the left colon and rectum(P=0.04).CONCLUSION PSC-UC represents a distinct form of IBD.The different disease phenotype in PSC-IBD patients with OLT may support liver-gut axis interaction,however warrants clinical attention and further research.展开更多
BACKGROUND Angiosarcoma is a highly malignant soft-tissue sarcoma derived from vascular endothelial cells that mainly occurs in the skin and subcutaneous tissues.Smallintestinal angiosarcomas are rare,and the prognosi...BACKGROUND Angiosarcoma is a highly malignant soft-tissue sarcoma derived from vascular endothelial cells that mainly occurs in the skin and subcutaneous tissues.Smallintestinal angiosarcomas are rare,and the prognosis is poor.CASE SUMMARY We reported a case of primary multifocal ileal angiosarcoma and analyze previously reported cases to improve our understanding of small intestinal angiosarcoma.Small intestinal angiosarcoma is more common in elderly and male patients.Gastrointestinal bleeding,anemia,abdominal pain,weakness,and weight loss were the common symptoms.CD31,CD34,factor VIII-related antigen,ETS-related gene,friend leukemia integration 1,and von Willebrand factor are valuable immunohistochemical markers for the diagnosis of small-intestinal angiosarcoma.Small-intestinal angiosarcoma most commonly occurs in the jejunum,followed by the ileum and duodenum.Radiation and toxicant exposure are risk factors for angiosarcoma.After a definite diagnosis,the mean and median survival time was 8 mo and 3 mo,respectively.Kaplan-Meier survival analysis showed that age,infiltration depth,chemotherapy,and the number of small intestinal segments invaded by tumor lesions were prognostic factors for small intestinal angiosarcoma.Multivariate Cox regression analysis showed that chemotherapy and surgery significantly improved patient prognosis.CONCLUSION Angiosarcoma should be considered for unexplained melena and abdominal pain,especially in older men and patients with a history of radiation exposure.Prompt treatment,including surgery and adjuvant chemotherapy,is essential to prolonging patient survival.展开更多
BACKGROUND Primary sclerosing cholangitis(PSC)manifests within a broad ethnic and racial spectrum,reflecting different levels of access to health care.AIM To evaluate the clinical profile,complications and survival ra...BACKGROUND Primary sclerosing cholangitis(PSC)manifests within a broad ethnic and racial spectrum,reflecting different levels of access to health care.AIM To evaluate the clinical profile,complications and survival rates of patients with PSC undergoing liver transplantation(LTx)at a Brazilian reference center.METHODS All patients diagnosed with PSC before or after LTx were included.The medical records were reviewed for demographic and clinical variables,including outcomes and survival.The level of statistical significance was set at P<0.05.RESULTS Our cohort represented 1.6%(n=34)of the 2113 patients receiving liver grafts at our service over the past two decades.Most were male(n=19;56%).The average age(40±14 years)was similar for men and women(P=0.347).The mean follow-up time from diagnosis to LTx was 68 mo.Most patients had the classic form of PSC.Three women had PSC/autoimmune hepatitis overlap syndrome,and one patient had small-duct PSC.Alkaline phosphatase levels at diagnosis and pre-LTx model for end-stage liver disease.scores were significantly higher in males.Inflammatory bowel research(IBD)was investigated by colonoscopy in 26/34(76%)and was present in most cases(18/26;69%).IBD was less common in women than in men(44.4%vs.55.6%)(P=0.692).Cholangiocarcinoma(CCA)was diagnosed in 2/34(5.9%)patients by histopathology of the explant(survival:3 years 6 mo,and 4 years 11 mo).Two patients had complications requiring a second LTx(one after 7 d due to hepatic artery thrombosis and one after 17 d due to primary graft dysfunction).Five patients(14.7%)developed biliary stricture.The overall median post-LTx survival was 66 mo.Most deaths occurred in the first year(infection n=2,primary liver graft dysfunction n=3,unknown cause n=1).The 1-year and 5-year survival rates of this cohort were 82.3%and 70.6%,respectively,matching the mean overall survival rates of LTx patients at our center(87.1%and 69.43%,respectively)(P=0.83).CONCLUSION Survival after 1 and 5 years was similar to that of other LTx indications.The observed CCA survival rate suggests CCA may be an indication for LTx in selected cases.展开更多
BACKGROUND Myxopapillary ependymoma(MPE)is a pathological grade I tumor that arises in the filum terminale.MPE with anaplastic features is extremely rare,and only 5 cases have shown malignancy at the time of recurrenc...BACKGROUND Myxopapillary ependymoma(MPE)is a pathological grade I tumor that arises in the filum terminale.MPE with anaplastic features is extremely rare,and only 5 cases have shown malignancy at the time of recurrence.CASE SUMMARY The patient(a 46-year-old woman)had undergone a MPE operation 30 years ago.After subtotal resection of the tumor located in L4-S1,it had a solid component that extended to the adjacent subcutaneous region.Histologically,the tumor consisted of a typical MPE with anaplastic features.The anaplastic areas of the tumor showed hypercellularity,a rapid mitotic rate,vascular proliferation,and connective tissue proliferation.Pleomorphic cells and atypical mitotic figures were occasionally observed.The MIB-1 index in this area was 12.3%.The immunohistochemical study showed immunoreactivity for vimentin,glial fibrillary acidic protein and S100.The morphological pattern and immunohistochemical profile were consistent with anaplastic MPE.The patient tolerated surgery well without new neurological deficits.She underwent local irradiation for the residual tumor and rehabilitation.CONCLUSION Although extremely rare,anaplastic MPE occurs in both pediatric and adult patients,similar to other ependymomas.At a minimum,close monitoring is recommended,given concerns about aggressive biological potential.In the future,further study is needed to determine the WHO classification criteria and genetic indicators of tumor progression.The possibility of malignant transformation of MPE should be taken into account,and patients with MPE should be treated with care and follow-up.展开更多
Ki67 is a marker of cell proliferation that is expressed in the S, G2 and M phases but not in the G0 phase of the cell cycle. Several recent studies showed that the expression of Ki67 is closely related to the occurre...Ki67 is a marker of cell proliferation that is expressed in the S, G2 and M phases but not in the G0 phase of the cell cycle. Several recent studies showed that the expression of Ki67 is closely related to the occurrence and development of gastrointestinal tumours. The Ki67 index is closely related to the degree of differentiation, invasion, metastasis and prognosis of gastrointestinal tumours. This review describes the relationship between the Ki67 index and degree of malignancy, therapeutic effect and prognosis of gastrointestinal tumours.展开更多
Background:Ductal carcinoma in situ with microinvasion(DCIS-MI)is defined as ductal carcinoma in situ(DCIS)with a microscopic invasive focus≤1 mm in the longest diameter.The current literature is controversial concer...Background:Ductal carcinoma in situ with microinvasion(DCIS-MI)is defined as ductal carcinoma in situ(DCIS)with a microscopic invasive focus≤1 mm in the longest diameter.The current literature is controversial concerning the clinical prognostic features and management of DCIS-MI.This narrative review described recently reported literature regarding the characteristics,treatment,and prognosis of it.Methods:Searching PubMed for relevant articles covering the period of 1982 to 2021 using the following terms by MeSH and free-word:breast cancer,microinvasion,DCIS,DCIS-MI,and invasive ductal carcinoma(IDC).Results:DCIS-MI tends to express more aggressive pathological features such as necrosis,HER2+,ER-or PR-,and high nuclear grade.The overall prognosis of DCIS-MI is typically good,however,some indicators such as young age,HR-,HER2+and multimicroinvasive lesions,were associated with worse prognoses.And there are also conflicting results on the differences between the prognoses of DCIS-MI and DCIS or T1a-IDC.Postoperative chemotherapy and anti-HER2 therapy still have uncertain benefits and are more likely to be used to treat high-risk patients who are HR-orHER2+to improve the prognosis.Conclusion:DCIS-MI has more aggressive pathological features,which may suggest its biological behavior is worse than that of DCIS and similar to early IDC.Although the overall prognosis of DCIS-MI is good,when making decisions about adjuvant therapy clinicians need to give priority to the hormone receptor status,HER2 expression and axillary lymph node status of patients,because these may affect the prognosis and treatment response.展开更多
Background:Hepatocellular carcinoma(HCC)is one of the most common causes of cancer worldwide.Although many studies have focused on oncogene characteristics,the genomic landscape of Chinese HCC patients has not been fu...Background:Hepatocellular carcinoma(HCC)is one of the most common causes of cancer worldwide.Although many studies have focused on oncogene characteristics,the genomic landscape of Chinese HCC patients has not been fully clarified.Methods:A total of 165 HCC patients,including 146 males and 19 females,were enrolled.The median age was 55 years(range,27-78 years).Corresponding clinical and pathological information was collected for further analysis.A total of 168 tumor tissues from these patients were selected for next-generation sequencing(NGS)-based 450 panel gene sequencing.Genomic alterations including single nucleotide variations(SNV),short and long insertions and deletions(InDels),copy number variations,and gene rearrangements were analyzed.Tumor mutational burden(TMB)was measured by an algorithm developed in-house.The top quartile of HCC was classified as TMB high.Results:A total of 1,004 genomic alterations were detected from 258 genes in 168 HCC tissues.TMB values were identified in 160 HCC specimens,with a median TMB of 5.4 Muts/Mb(range,0-28.4 Muts/Mb)and a 75%TMB of 7.7 Muts/Mb.The most commonly mutated genes were TP53,TERT,CTNNB1,AXIN1,RB1,TSC2,CCND1,ARID1A,and FGF19.SNV was the most common mutation type and C:G>T:A and guanine transformation were the most common SNVs.Compared to wild-type patients,the proportion of Edmondson grade III-IV and microvascular invasion was significantly higher in TP53 mutated patients(P<0.05).The proportion of tumors invading the hepatic capsule was significantly higher in TERT mutated patients(P<0.05).The proportion of Edmondson grade I-II,alpha fetoprotein(AFP)<25μmg/L,and those without a history of hepatitis B was significantly higher in CTNNB1 mutated patients(P<0.05).CTNNB1 mutations were associated with TMB high in HCC patients(P<0.05).Based on correlation analysis,the mutation of TP53 was independently correlated with microvascular invasion(P=0.002,OR=3.096)and Edmondson grade III-IV(P=0.008,OR=2.613).The mutation of TERT was independently correlated with tumor invasion of the liver capsule(P=0.001,OR=3.030),and the mutation of CTNNB1 was independently correlated with AFP(<25μmg/L)(P=0.009,OR=3.414).Conclusions:The most frequently mutated genes of HCC patients in China were TP53,TERT,and CTNNB1,which mainly lead to the occurrence and development of HCC by regulating the P53 pathway,Wnt pathway,and telomere repair pathway.There were more patients with microvascular invasion and Edmondson III-IV grade in TP53 mutated patients and more patients with hepatic capsule invasion in TERT mutated patients,while in CTNNB1 mutated patients,there were more patients with Edmondson I-II grade,AFP<25μmg/L,and a non-hepatitis B background.Also,the TMB values were significantly higher in CTNNB1 mutated patients than in wild type patients.展开更多
基金Supported by the National Natural Science Foundation of China,No.U1504815
文摘AIM To investigate the relationship between autophagy and perineural invasion(PNI), clinical features, and prognosis in patients with pancreatic cancer. METHODS Clinical and pathological data were retrospectively collected from 109 patients with pancreatic ductal adenocarcinoma who underwent radical resection at the First Affiliated Hospital of Zhengzhou University from January 2011 to August 2016. Expression levels of the autophagy-related protein microtubuleassociated protein 1 A/1 B-light chain 3(LC3) and PNI marker ubiquitin carboxy-terminal hydrolase(UCH) in pancreatic cancer tissues were detected by immunohistochemistry. The correlations among LC3 expression, PNI, and clinical pathological features in pancreatic cancer were analyzed. The patients were followed for further survival analysis. RESULTS In 109 cases of pancreatic cancer, 68.8%(75/109) had evidence of PNI and 61.5%(67/109) had high LC3 expression. PNI was associated with lymph node metastasis, pancreatitis, and CA19-9 levels(P < 0.05). LC3 expression was related to lymph node metastasis(P < 0.05) and was positively correlated with neural invasion(P < 0.05, r = 0.227). Multivariate logistic regression analysis indicated that LC3 expression, lymph node metastasis, pancreatitis, and CA19-9 level were factors that influenced neural invasion, whereas only neural invasion itself was an independent factor for high LC3 expression. Univariate analysis showed that LC3 expression, neural invasion, and CA19-9 level were related to the overall survival of pancreatic cancer patients(P < 0.05). Multivariate COX regression analysis indicated that PNI and LC3 expression were independent risk factors for poor prognosis in pancreatic cancer(P < 0.05). CONCLUSION PNI in patients with pancreatic cancer is positively related to autophagy. Neural invasion and LC3 expression are independent risk factors for pancreatic cancer with a poor prognosis.
文摘BACKGROUND Breast cancer is the most common malignancy in women all around the world.According to the latest statistics in 2018,there were more than 2.08 million new breast cancer cases all around the world and more than 620000 deaths;the proportion of breast cancer deaths in women with cancer is 15%.By studying age,clinicopathological characteristics and molecular classification,age at menarche,age at birth,number of births,number of miscarriages,lactation time,surgical history of benign breast lesions,history of gynecological diseases,and other factors,we retrospectively summarized and compared the disease history of patients with primary breast cancer and patients with benign thyroid tumors admitted to our hospital in the past 10 years to explore the clinicopathological characteristics and risk factors for primary breast cancer.AIM To investigate the clinical and pathological features and risk factors for primary breast cancer treated at our center in order to provide a reference for the prevention and treatment of breast cancer in the Zhuhai-Macao region.METHODS Through a retrospective case-control study,149 patients with primary breast cancer diagnosed and treated at Zhuhai Hospital of Guangdong Provincial Hospital of Traditional Chinese Medicine from January 2013 to March 2020 were included as a case group,and 165 patients with benign breast tumors diagnosed and treated from January 2019 to March 2020 were included as a control group.The data collected included age,age at menarche,age at first birth,number of births,number of miscarriages,lactation time,history of surgery for benign breast lesions,history of familial malignant tumors,history of gynecological diseases,history of thyroid diseases,and the tumor characteristics of the patients in the case group including pathological diagnosis,pathological type,tumor size,lymph node metastasis,distant metastasis,stage,and molecular classification,among others.In the case group,the chi-square test was used to analyze the clinical and pathological features of patients in three age groups(<40,40-59,and≥60 years).A multifactor logistic regression analysis was used to analyze correlations between the two groups.RESULTS Among 149 patients with primary breast cancer,the average age was 48.20±12.06 years,and the proportion of patients at 40-59 years old was the highest,accounting for 61.8%of cases.The molecular type was mainly luminal B type,accounting for 69.2%of cases,and at the time of diagnosis,the tumor stage was mainly stage I/II,accounting for 62.4%of cases.There were no statistically significant differences in the distributions of tumor location,pathological type,tumor size,lymph node metastasis,stage,or molecular classification among the three age groups(<40,40-59,and≥60 years)(P≥0.05).The differences in the distribution of distant metastasis among the three age groups(<40,40-59,and≥60 years)were statistically significant(P<0.01).The differences in lactation time,history of familial malignant tumors,history of gynecological diseases,and history of thyroid diseases between the two groups were not statistically significant(P≥0.05).The differences in age at disease diagnosis,age at menarche,and history of surgery for benign breast lesions were statistically significant(P<0.01).The difference in age at first birth was also statistically significant(P<0.05).CONCLUSION The highest incidence of breast cancer in the Zhuhai-Macao region is present among women aged 40-59 years.There is a larger proportion of stage I/II patients,and the luminal B type is the most common molecular subtype.Distant metastasis occurs mainly in the≥60-year-old group at the first diagnosis;increased age,late age at menarche,and late age at first birth may be risk factors for primary breast cancer,and a history of surgery for benign breast lesions may be a protective factor for primary breast cancer.
文摘BACKGROUND: Devic's neuromyelitis optica (DNMO) and multiple sclerosis in Asian populations have been considered to be the same disease. However, there is an increasing number of studies suggesting that DNMO and multiple sclerosis are different diseases. OBJECTIVE: Little information is available regarding comparisons of DNMO patients between China and other countries, as well as clinical manifestations of Chinese patients with DNMO and multiple sclerosis. The present study performed a multicenter, pathological, retrospective analysis. DESIGN, TIME AND SETTING: A retrospective analysis of clinical data from seven patients with DNMO diagnosed between 1957 and 1998. PARTICIPANTS: Data from Chinese DNMO patients was provided by the Shanghai Second Medical University, Sun Yat-sen University of Medical Sciences and the First Affiliated Hospital of Harbin Medical University in China. METHODS: Clinical and pathological data from Chinese patients with DNMO were retrospectively analyzed. The clinical characteristics of DNMO were compared between Chinese and Caucasian patients. In addition, clinical and pathological differences between DNMO and multiple sclerosis Chinese patients were compared. MAIN OUTCOME MEASURES: Clinical and pathological features of Chinese patients with DNMO. RESULTS: All seven Chinese patients with DNMO exhibited abrupt onset of vision disturbance, with a disease course of 3 days to 9 years. DNMO recurred in two of the patients. Demyelinating lesions were observed in all patients, with necrotic lesions and gitter cells in five patients, collagenous hyperplasia in one patient, and perivascular inflammatory cell infiltration in six patients. Comparison between Chinese and Caucasian DNMO patients revealed no significant differences in age at onset, clinical onset, duration, or interval between optic neuritis and myelitis. Compared with Chinese multiple sclerosis patients, Chinese DNMO patients presented with fewer recurrences, higher occurrence of necrosis, perivascular inflammatory cell infiltration and gitter cells, and a lower occurrence of collagenous hyperplasia. CONCLUSION: There was no difference in DNMO clinical features between Chinese and Caucasian patients. However, the clinical and pathological features of DNMO were different compared with multiple sclerosis in Chinese patients. Results suggested that the characteristics of DNMO in Chinese patients were significantly different than multiple sclerosis.
基金Natural Science Foundation of Liaoning Province,China,No.2022-YGJC-71
文摘BACKGROUND Endoscopy has rapidly developed in recent years and has enabled further investigation into the origin and features of intestinal tumors.The small size and concealed position of these tumors make it difficult to distinguish them from nonneoplastic polyps and carcinoma in adenoma(CIA).The invasive depth and metastatic potential determine the operation regimen,which in turn affects the overall survival and distant prognosis.The previous studies have confirmed the malignant features and clinicopathological features of de novo colorectal cancer(CRC).AIM To provide assistance for diagnosis and treatment,but the lack of a summary of endoscopic features and assessment of risk factors that differ from the CIA prompted us to conduct this retrospective study.METHODS In total,167 patients with small-sized CRCs diagnosed by endoscopy were reviewed.The patients diagnosed as advanced CRCs and other malignant cancers or chronic diseases that could affect distant outcomes were excluded.After screening,63 cases were excluded,including 33 de novo and 30 CIA cases.Patient information,including their follow-up information,was obtained from an electronic His-system.The characteristics between two group and risk factors for invasion depth were analyzed with SPSS 25.0 software.RESULTS Nearly half of the de novo CRCs were smaller than 1 cm(n=16,48.5%)and the majority were located in the distal colon(n=26,78.8%).The IIc type was the most common macroscopic type of de novo CRC.In a Pearson analysis,the differential degree,Sano,JNET,and Kudo types,surrounding mucosa,and chicken skin mucosa(CSM)were correlated with the invasion depth(P<0.001).CSM was a significant risk factor for deep invasion and disturbed judgment of endoscopic ultrasound.A high degree of tumor budding and tumor-infiltrating lymphocytes are accompanied by malignancy.Finally,de novo CRCs have worse outcomes than CIA CRCs.CONCLUSION This is the first comprehensive study to analyze the features of de novo CRCs to distinguish them from nonneoplastic polyps.It is also the first study paying attention to CSM invasive depth measurement.This study emphasizes the high metastatic potential of de novo CRCs and highlights the need for more research on this tumor type.
基金Supported by National Natural Science Foundation of China,No.81860433Natural Science Youth Foundation of Jiangxi Province,No.20192BAB215036+2 种基金Jiangxi Province Natural Science Key R&D Project-General Project,No.20202BBG73024Training Plan for Academic and Technical Young Leaders of Major Disciplines in Jiangxi Province,No.20204BCJ23021Jiangxi Provincial Education Department,Science and Technology Research Project-Youth Project,No.GJJ210252。
文摘BACKGROUND The clinicopathological features and prognosis of gastric signet ring cell carcinoma(GSRC)remain controversial,particularly with regard to sensitivity to postoperative adjuvant therapy.AIM To compare the pathological features of GSRC with those of gastric adenocarcinoma of different degrees of differentiation and the differences in survival prognosis between the different disease processes.METHODS By screening gastric cancer patients from 2010 to 2015 in the database of Surveillance,Epidemiology and End Results,and collecting the clinicopathological and prognostic data of gastric cancer patients who underwent surgery from January 2014 to December 2016 in the Second Affiliated Hospital of Nanchang University,we analyzed the general pathological characteristics of GSRC by the chi-square test.Univariate and multivariate analyses were conducted to compare the factors affecting the survival and prognosis of early and advanced gastric adenocarcinoma.The Kaplan-Meier curves were plotted to reveal the survival difference between early and advanced GSRC and different differentiated types of gastric adenocarcinoma.The prognosis model of advanced GSRC was established with R software,and the area under curve(AUC)and C-index were used to assess the accuracy of the model.RESULTS Analysis of pathological features revealed that signet ring-cell carcinoma(SRC)was more frequently seen in younger(<60 years),female,and White patients compared to non-SRC patients.SRC was less commonly associated with early gastric cancer(EGC)(23.60%vs 39.10%),lower N0(38.61%vs 61.03%),and larger tumour sizes>5 cm(31.15%vs 27.10%)compared to the differentiated type,while the opposite was true compared to the undifferentiated type.Survival prognostic analysis found no significant difference in the prognosis of SRC patients among EGC patients.In contrast,among advanced gastric cancer(AGC)patients,the prognosis of SRC patients was correlated with age,race,tumour size,AJCC stage,T-stage,and postoperative adjuvant therapy.The predictive model showed that the 3-year AUC was 0.787,5-year AUC was 0.806,and C-index was 0.766.Compared to non-SRC patients,patients with SRC had a better prognosis in EGC[hazard ratio(HR):0.626,95%confidence interval(CI):0.427-0.919,P<0.05]and a worse prognosis in AGC(HR:1.139,95%CI:1.030-1.258,P<0.05).When non-SRC was divided into differentiated and undifferentiated types for comparison,it was found that in EGC,SRC had a better prognosis than differentiated and undifferentiated types,while there was no significant difference between differentiated and undifferentiated types.In AGC,there was no significant difference in prognosis between SRC and undifferentiated types,both of which were worse than differentiated types.A prognostic analysis of postoperative adjuvant therapy for SRC in patients with AGC revealed that adjuvant postoperative radiotherapy or chemotherapy significantly improved patient survival(34.6%and 36.2%vs 18.6%,P<0.05).CONCLUSION The prognosis of SRC is better than that of undifferentiated type,especially in EGC,and its prognosis is even better than that of differentiated type.SRC patients can benefit from early detection,surgical resection,and aggressive adjuvant therapy.
基金Scientific research project of Jiangsu Health and Family Planning Commission(No.H2017082)。
文摘Objective:To investigate the effect of programmed death-ligand 1(PD-L1)gene polymorphism on pathological characteristics and clinical prognosis quality in patients with esophageal cancer.Methods:86 patients with esophageal cancer treated in our hospital from January 2014 to January 2017 were selected as the observation group,and 100 healthy patients were selected as the control group during the same period.The single nucleotide polymorphisms of rs2890658,rs17718883,rs2297136 and rs4143185 at different sites were determined.And the impact of PD-L1 gene polymorphism on pathological features and prognosis of esophageal cancer were analyzed.Results:The observation group finally completed 84 cases,and the control group included 99 cases.There were differences between the observation group and the control group in the PD-L1 different genetic locus rs17718883,rs2890658,rs2297136(P<0.05).The PD-L1 locus rs17718883 was related to the pathological type and degree of differentiation of esophageal cancer,the difference was statistically significant(P<0.05),rs2890658 was related to the degree of differentiation of esophageal cancer,the difference was statistically significant(P<0.05).Log-rank test showed that the genotype of rs17718883 in patients with esophageal cancer was related to prognostic survival,and the difference was statistically significant(P<0.05).Cox proportional hazards model analysis showed that age,degree of differentiation,lymph node metastasis,and rs17718883 genotype were independent factors in the prognosis of patients with esophageal cancer,and the difference was statistically significant(P<0.05).Conclusion:The polymorphisms of rs17718883 and rs2890658 loci of PD-L1 gene have an impact on the clinicopathological characteristics of patients with esophageal cancer,and the polymorphisms of rs17718883 locus of PD-L1 gene have an impact on the clinical prognosis quality.
文摘BACKGROUND Primary sclerosing cholangitis(PSC)associated inflammatory bowel disease(IBD)is a unique form of IBD(PSC-IBD)with distinct clinical and histologic features from ulcerative colitis(UC)and Crohn disease(CD).In patients with PSC and IBD,the severity of the two disease processes may depend on each other.AIM To study the histologic and clinical features of PSC patients with and without IBD.METHODS We assessed specimens from patients with UC(n=28),CD(n=10),PSC and UC(PSC-UC;n=26);PSC and CD(PSC-CD;n=6);and PSC and no IBD(PSC-no IBD;n=4)between years 1999-2013.PSC-IBD patients were matched to IBD patients without PSC by age and colitis duration.Clinical data including age,gender,age at IBD and PSC diagnoses,IBD duration,treatment,follow-up,orthotopic liver transplantation(OLT)were noted.RESULTS PSC-UC patients had more isolated right-sided disease(P=0.03),and less active inflammation in left colon,rectum(P=0.03 and P=0.0006),and overall(P=0.0005)compared to UC.They required less steroids(P=0.01)and fewer colectomies(P=0.03)than UC patients.The PSC-CD patients had more ileitis and less rectal involvement compared to PSC-UC and CD.No PSC-CD patients required OLT compared to 38%of PSC-UC(P=0.1).PSC-IBD(PSC-UC and PSCCD)patients with OLT had severe disease in the left colon and rectum(P=0.04).CONCLUSION PSC-UC represents a distinct form of IBD.The different disease phenotype in PSC-IBD patients with OLT may support liver-gut axis interaction,however warrants clinical attention and further research.
文摘BACKGROUND Angiosarcoma is a highly malignant soft-tissue sarcoma derived from vascular endothelial cells that mainly occurs in the skin and subcutaneous tissues.Smallintestinal angiosarcomas are rare,and the prognosis is poor.CASE SUMMARY We reported a case of primary multifocal ileal angiosarcoma and analyze previously reported cases to improve our understanding of small intestinal angiosarcoma.Small intestinal angiosarcoma is more common in elderly and male patients.Gastrointestinal bleeding,anemia,abdominal pain,weakness,and weight loss were the common symptoms.CD31,CD34,factor VIII-related antigen,ETS-related gene,friend leukemia integration 1,and von Willebrand factor are valuable immunohistochemical markers for the diagnosis of small-intestinal angiosarcoma.Small-intestinal angiosarcoma most commonly occurs in the jejunum,followed by the ileum and duodenum.Radiation and toxicant exposure are risk factors for angiosarcoma.After a definite diagnosis,the mean and median survival time was 8 mo and 3 mo,respectively.Kaplan-Meier survival analysis showed that age,infiltration depth,chemotherapy,and the number of small intestinal segments invaded by tumor lesions were prognostic factors for small intestinal angiosarcoma.Multivariate Cox regression analysis showed that chemotherapy and surgery significantly improved patient prognosis.CONCLUSION Angiosarcoma should be considered for unexplained melena and abdominal pain,especially in older men and patients with a history of radiation exposure.Prompt treatment,including surgery and adjuvant chemotherapy,is essential to prolonging patient survival.
基金reviewed and approved by the ethics committee of the Federal University of Cearáand filed under Approval No.98627218.6.2018.5045.
文摘BACKGROUND Primary sclerosing cholangitis(PSC)manifests within a broad ethnic and racial spectrum,reflecting different levels of access to health care.AIM To evaluate the clinical profile,complications and survival rates of patients with PSC undergoing liver transplantation(LTx)at a Brazilian reference center.METHODS All patients diagnosed with PSC before or after LTx were included.The medical records were reviewed for demographic and clinical variables,including outcomes and survival.The level of statistical significance was set at P<0.05.RESULTS Our cohort represented 1.6%(n=34)of the 2113 patients receiving liver grafts at our service over the past two decades.Most were male(n=19;56%).The average age(40±14 years)was similar for men and women(P=0.347).The mean follow-up time from diagnosis to LTx was 68 mo.Most patients had the classic form of PSC.Three women had PSC/autoimmune hepatitis overlap syndrome,and one patient had small-duct PSC.Alkaline phosphatase levels at diagnosis and pre-LTx model for end-stage liver disease.scores were significantly higher in males.Inflammatory bowel research(IBD)was investigated by colonoscopy in 26/34(76%)and was present in most cases(18/26;69%).IBD was less common in women than in men(44.4%vs.55.6%)(P=0.692).Cholangiocarcinoma(CCA)was diagnosed in 2/34(5.9%)patients by histopathology of the explant(survival:3 years 6 mo,and 4 years 11 mo).Two patients had complications requiring a second LTx(one after 7 d due to hepatic artery thrombosis and one after 17 d due to primary graft dysfunction).Five patients(14.7%)developed biliary stricture.The overall median post-LTx survival was 66 mo.Most deaths occurred in the first year(infection n=2,primary liver graft dysfunction n=3,unknown cause n=1).The 1-year and 5-year survival rates of this cohort were 82.3%and 70.6%,respectively,matching the mean overall survival rates of LTx patients at our center(87.1%and 69.43%,respectively)(P=0.83).CONCLUSION Survival after 1 and 5 years was similar to that of other LTx indications.The observed CCA survival rate suggests CCA may be an indication for LTx in selected cases.
文摘BACKGROUND Myxopapillary ependymoma(MPE)is a pathological grade I tumor that arises in the filum terminale.MPE with anaplastic features is extremely rare,and only 5 cases have shown malignancy at the time of recurrence.CASE SUMMARY The patient(a 46-year-old woman)had undergone a MPE operation 30 years ago.After subtotal resection of the tumor located in L4-S1,it had a solid component that extended to the adjacent subcutaneous region.Histologically,the tumor consisted of a typical MPE with anaplastic features.The anaplastic areas of the tumor showed hypercellularity,a rapid mitotic rate,vascular proliferation,and connective tissue proliferation.Pleomorphic cells and atypical mitotic figures were occasionally observed.The MIB-1 index in this area was 12.3%.The immunohistochemical study showed immunoreactivity for vimentin,glial fibrillary acidic protein and S100.The morphological pattern and immunohistochemical profile were consistent with anaplastic MPE.The patient tolerated surgery well without new neurological deficits.She underwent local irradiation for the residual tumor and rehabilitation.CONCLUSION Although extremely rare,anaplastic MPE occurs in both pediatric and adult patients,similar to other ependymomas.At a minimum,close monitoring is recommended,given concerns about aggressive biological potential.In the future,further study is needed to determine the WHO classification criteria and genetic indicators of tumor progression.The possibility of malignant transformation of MPE should be taken into account,and patients with MPE should be treated with care and follow-up.
文摘Ki67 is a marker of cell proliferation that is expressed in the S, G2 and M phases but not in the G0 phase of the cell cycle. Several recent studies showed that the expression of Ki67 is closely related to the occurrence and development of gastrointestinal tumours. The Ki67 index is closely related to the degree of differentiation, invasion, metastasis and prognosis of gastrointestinal tumours. This review describes the relationship between the Ki67 index and degree of malignancy, therapeutic effect and prognosis of gastrointestinal tumours.
文摘Background:Ductal carcinoma in situ with microinvasion(DCIS-MI)is defined as ductal carcinoma in situ(DCIS)with a microscopic invasive focus≤1 mm in the longest diameter.The current literature is controversial concerning the clinical prognostic features and management of DCIS-MI.This narrative review described recently reported literature regarding the characteristics,treatment,and prognosis of it.Methods:Searching PubMed for relevant articles covering the period of 1982 to 2021 using the following terms by MeSH and free-word:breast cancer,microinvasion,DCIS,DCIS-MI,and invasive ductal carcinoma(IDC).Results:DCIS-MI tends to express more aggressive pathological features such as necrosis,HER2+,ER-or PR-,and high nuclear grade.The overall prognosis of DCIS-MI is typically good,however,some indicators such as young age,HR-,HER2+and multimicroinvasive lesions,were associated with worse prognoses.And there are also conflicting results on the differences between the prognoses of DCIS-MI and DCIS or T1a-IDC.Postoperative chemotherapy and anti-HER2 therapy still have uncertain benefits and are more likely to be used to treat high-risk patients who are HR-orHER2+to improve the prognosis.Conclusion:DCIS-MI has more aggressive pathological features,which may suggest its biological behavior is worse than that of DCIS and similar to early IDC.Although the overall prognosis of DCIS-MI is good,when making decisions about adjuvant therapy clinicians need to give priority to the hormone receptor status,HER2 expression and axillary lymph node status of patients,because these may affect the prognosis and treatment response.
文摘Background:Hepatocellular carcinoma(HCC)is one of the most common causes of cancer worldwide.Although many studies have focused on oncogene characteristics,the genomic landscape of Chinese HCC patients has not been fully clarified.Methods:A total of 165 HCC patients,including 146 males and 19 females,were enrolled.The median age was 55 years(range,27-78 years).Corresponding clinical and pathological information was collected for further analysis.A total of 168 tumor tissues from these patients were selected for next-generation sequencing(NGS)-based 450 panel gene sequencing.Genomic alterations including single nucleotide variations(SNV),short and long insertions and deletions(InDels),copy number variations,and gene rearrangements were analyzed.Tumor mutational burden(TMB)was measured by an algorithm developed in-house.The top quartile of HCC was classified as TMB high.Results:A total of 1,004 genomic alterations were detected from 258 genes in 168 HCC tissues.TMB values were identified in 160 HCC specimens,with a median TMB of 5.4 Muts/Mb(range,0-28.4 Muts/Mb)and a 75%TMB of 7.7 Muts/Mb.The most commonly mutated genes were TP53,TERT,CTNNB1,AXIN1,RB1,TSC2,CCND1,ARID1A,and FGF19.SNV was the most common mutation type and C:G>T:A and guanine transformation were the most common SNVs.Compared to wild-type patients,the proportion of Edmondson grade III-IV and microvascular invasion was significantly higher in TP53 mutated patients(P<0.05).The proportion of tumors invading the hepatic capsule was significantly higher in TERT mutated patients(P<0.05).The proportion of Edmondson grade I-II,alpha fetoprotein(AFP)<25μmg/L,and those without a history of hepatitis B was significantly higher in CTNNB1 mutated patients(P<0.05).CTNNB1 mutations were associated with TMB high in HCC patients(P<0.05).Based on correlation analysis,the mutation of TP53 was independently correlated with microvascular invasion(P=0.002,OR=3.096)and Edmondson grade III-IV(P=0.008,OR=2.613).The mutation of TERT was independently correlated with tumor invasion of the liver capsule(P=0.001,OR=3.030),and the mutation of CTNNB1 was independently correlated with AFP(<25μmg/L)(P=0.009,OR=3.414).Conclusions:The most frequently mutated genes of HCC patients in China were TP53,TERT,and CTNNB1,which mainly lead to the occurrence and development of HCC by regulating the P53 pathway,Wnt pathway,and telomere repair pathway.There were more patients with microvascular invasion and Edmondson III-IV grade in TP53 mutated patients and more patients with hepatic capsule invasion in TERT mutated patients,while in CTNNB1 mutated patients,there were more patients with Edmondson I-II grade,AFP<25μmg/L,and a non-hepatitis B background.Also,the TMB values were significantly higher in CTNNB1 mutated patients than in wild type patients.
