BACKGROUND Esophageal squamous cell carcinoma(ESCC)is a deadly malignancy with limited treatment options.Deubiquitinases(DUBs)have been confirmed to play a crucial role in the development of malignant tumors.JOSD2 is ...BACKGROUND Esophageal squamous cell carcinoma(ESCC)is a deadly malignancy with limited treatment options.Deubiquitinases(DUBs)have been confirmed to play a crucial role in the development of malignant tumors.JOSD2 is a DUB involved in con-trolling protein deubiquitination and influencing critical cellular processes in cancer.AIM To investigate the impact of JOSD2 on the progression of ESCC.METHODS Bioinformatic analyses were employed to explore the expression,prognosis,and enriched pathways associated with JOSD2 in ESCC.Lentiviral transduction was utilized to manipulate JOSD2 expression in ESCC cell lines(KYSE30 and RESULTS )Preliminary research indicated that JOSD2 was highly expressed in ESCC tissues,which was associated with poor prognosis.Further analysis demonstrated that JOSD2 was upregulated in ESCC cell lines compared to normal esophageal cells.JOSD2 knockdown inhibited ESCC cell activity,including proliferation and colony-forming ability.Moreover,JOSD2 knockdown decreased the drug resistance and migration of ESCC cells,while JOSD2 overexpression enhanced these phenotypes.In vivo xenograft assays further confirmed that JOSD2 promoted tumor proliferation and drug resistance in ESCC.Mechanistically,JOSD2 appears to activate the MAPK/ERK and PI3K/AKT signaling pathways.Mass spectrometry was used to identify crucial substrate proteins that interact with JOSD2,which identified the four primary proteins that bind to JOSD2,namely USP47,IGKV2D-29,HSP90AB1,and PRMT5.CONCLUSION JOSD2 plays a crucial role in enhancing the proliferation,migration,and drug resistance of ESCC,suggesting that JOSD2 is a potential therapeutic target in ESCC.展开更多
In recent years,endoscopic resection,particularly endoscopic submucosal dis-section,has become increasingly popular in treating non-metastatic superficial esophageal squamous cell carcinoma(ESCC).In this evolving para...In recent years,endoscopic resection,particularly endoscopic submucosal dis-section,has become increasingly popular in treating non-metastatic superficial esophageal squamous cell carcinoma(ESCC).In this evolving paradigm,it is crucial to identify factors that predict higher rates of lymphatic invasion and poorer outcomes.Larger tumor size,deeper invasion,poorer differentiation,more infiltrative growth patterns(INF-c),higher-grade tumor budding,positive lymphovascular invasion,and certain biomarkers have been associated with lymph node metastasis and increased morbidity through retrospective reviews,leading to the construction of comprehensive nomograms for outcome prediction.If validated by future prospective studies,these nomograms would prove highly applicable in guiding the selection of treatment for superficial ESCC.展开更多
Objective:To explore and analyze the expression and clinical significance of vascular endothelial growth factor(VEGF),hypoxia-inducible factor 1α(HIF-1α),and metabolic indicators in esophageal squamous cell carcinom...Objective:To explore and analyze the expression and clinical significance of vascular endothelial growth factor(VEGF),hypoxia-inducible factor 1α(HIF-1α),and metabolic indicators in esophageal squamous cell carcinoma(ESCC).Methods:Sixty ESCC patients admitted to the hospital from October 2021 to October 2023 were selected as the ESCC group.Sixty normal healthy patients from the same period were chosen as the control group.Their serum samples and tissue samples were collected.Metabolic indicators of all study subjects were obtained based on the basic biochemical results upon admission.RT-PCR was utilized to detect the expression of VEGF and HIF-1αin ESCC tissues.Results:The expression of VEGF and HIF-1αin the ESCC T3+T4 group was significantly higher than that of the carcinoma in situ(Tis)group,T1+T2 group,and control group.Furthermore,the expression of HIF-1αwas found to be related to the expression of VEGF,showing a significant correlation between the quantities.Significant differences in the levels of metabolic indicators were observed between the ESCC group and the control group(P<0.05).Conclusion:Metabolic indicators are associated with the onset of ESCC in patients.Abnormal lipid metabolism plays a crucial role in the occurrence and development of tumors.The expression of VEGF and HIF-1αin ESCC tissues significantly correlates with the tumor stage,providing a new reference for the diagnosis and treatment of ESCC.展开更多
BACKGROUND Superficial esophageal squamous cell carcinoma(ESCC)is defined as cancer infiltrating the mucosa and submucosa,regardless of regional lymph node metastasis(LNM).Endoscopic resection of superficial ESCC is s...BACKGROUND Superficial esophageal squamous cell carcinoma(ESCC)is defined as cancer infiltrating the mucosa and submucosa,regardless of regional lymph node metastasis(LNM).Endoscopic resection of superficial ESCC is suitable for lesions that have no or low risk of LNM.Patients with a high risk of LNM always need further treatment after endoscopic resection.Therefore,accurately assessing the risk of LNM is critical for additional treatment options.AIM To analyze risk factors for LNM and develop a nomogram to predict LNM risk in superficial ESCC patients.METHODS Clinical and pathological data of superficial ESCC patients undergoing esophagectomy from January 1,2009 to January 31,2016 were collected.Logistic regression analysis was used to predict LNM risk factors,and a nomogram was developed based on risk factors derived from multivariate logistic regression analysis.The receiver operating characteristic(ROC)curve was used to obtain the accuracy of the nomogram model.RESULTSA total of 4660 patients with esophageal cancer underwent esophagectomy.Of these,474 superficial ESCC patientswere enrolled in the final analysis,with 322 patients in the training set and 142 patients in the validation set.Theprevalence of LNM was 3.29%(5/152)for intramucosal cancer and increased to 26.40%(85/322)for submucosalcancer.Multivariate logistic analysis showed that tumor size,invasive depth,tumor differentiation,infiltrativegrowth pattern,tumor budding,and lymphovascular invasion were significantly correlated with LNM.Anomogram using these six variables showed good discrimination with an area under the ROC curve of 0.789(95%CI:0.737-0.841)in the training set and 0.827(95%CI:0.755-0.899)in the validation set.CONCLUSIONWe developed a useful nomogram model to predict LNM risk for superficial ESCC patients which will facilitateadditional decision-making in treating patients who undergo endoscopic resection.展开更多
Esophageal cancer(EC)ranks among the most prevalent malignant tumors affecting the digestive tract.Esophageal squamous cell carcinoma(ESCC)stands as the prevailing pathological subtype,encompassing approximately 90%of...Esophageal cancer(EC)ranks among the most prevalent malignant tumors affecting the digestive tract.Esophageal squamous cell carcinoma(ESCC)stands as the prevailing pathological subtype,encompassing approximately 90%of all EC patients.In clinical stage II-IVA locally advanced ESCC cases,the primary approach to treatment involves a combination of neoadjuvant therapy and surgical resection.Despite concerted efforts,the long-term outcomes for ESCC patients remain unsatisfactory,with dismal prognoses.However,recent years have witnessed remarkable strides in immunotherapy,particularly in the secondand first-line treatment of advanced or metastatic ESCC,with the development of monoclonal antibodies that inhibit programmed death 1 or programmed death ligand 1 demonstrating encouraging responses and perioperative clinical benefits for various malignancies,including ESCC.This comprehensive review aims to present the current landscape of perioperative immunotherapy for resectable ESCC,focusing specifically on the role of immune checkpoint inhibitors during the perioperative period.Additionally,the review will explore promising biomarkers and offer insights into future prospects.展开更多
Esophageal squamous cell carcinoma(ESCC)is among the most prevalent causes of cancer-related death in patients worldwide.Resistance to immunotherapy and chemotherapy results in worse survival outcomes in ESCC.It is ur...Esophageal squamous cell carcinoma(ESCC)is among the most prevalent causes of cancer-related death in patients worldwide.Resistance to immunotherapy and chemotherapy results in worse survival outcomes in ESCC.It is urgent to explore the underlying molecular mechanism of immune evasion and chemoresistance in ESCC.Here,we conducted RNA-sequencing analysis in ten ESCC tissues from cisplatin-based neoadjuvant chemotherapy patients.We found that DMRTA1 was extremely upregulated in the non-pathologic complete response(non-pCR)group.The proliferation rate of esophageal squamous carcinoma cells was markedly decreased after knockdown of DMRTA1 expression,which could increase cisplatin sensitivity in ESCC.Additionally,suppression of DMRTA1 could decrease the immune escape of esophageal squamous carcinoma cells.Further mechanistic studies suggest that DMRTA1 can promote its expression by binding to the promoter of SOX2,which plays important roles in the progression and chemoresistance of ESCC in the form of positive feedback.Therefore,DMRTA1 could be a potential target to suppress immune escape and overcome chemoresistance in ESCC.展开更多
BACKGROUND Esophageal squamous cell carcinoma(ESCC)is causing a high mortality rate due to the lack of efficient early prognosis markers and suitable therapeutic regimens.The prognostic role of genes responsible for t...BACKGROUND Esophageal squamous cell carcinoma(ESCC)is causing a high mortality rate due to the lack of efficient early prognosis markers and suitable therapeutic regimens.The prognostic role of genes responsible for the acquisition of radioresistance in ESCC has not been fully elucidated.AIM To establish a prognostic model by studying gene expression patterns pertinent to radioresistance in ESCC patients.METHODS Datasets were obtained from the Gene Expression Omnibus and The Cancer Genome Atlas databases.The edgeR,a Bioconductor package,was used to analyze mRNA expression between different groups.We screened genes specifically responsible for radioresistance to estimate overall survival.Pearson correlation analysis was performed to confirm whether the expression of those genes correlated with each other.Genes contributing to radioresistance and overall survival were assessed by the multivariate Cox regression model through the calculation ofβi and risk score using the following formula:∑^(n)_(i=1)βi×PSI.RESULTS We identified three prognostic mRNAs(cathepsin S[CTSS],cluster of differentiation 180[CD180],and SLP adapter and CSK-interacting membrane protein[SCIMP])indicative of radioresistance.The expression of the three identified mRNAs was related to each other(r>0.70 and P<0.05).As to 1-year and 3-year overall survival prediction,the area under the time-dependent receiver operating characteristic curve of the signature consisting of the three mRNAs was 0.716 and 0.841,respectively.When stratifying patients based on the risk score derived from the signature,the high-risk group exhibited a higher death risk and shorter survival time than the low-risk group(P<0.0001).Overall survival of the low-risk patients was significantly better than that of the highrisk patients(P=0.018).CONCLUSION We have developed a novel three-gene prognostic signature consisting of CTSS,CD180,and SCIMO for ESCC,which may facilitate the prediction of early prognosis of this malignancy.展开更多
Accumulating evidence has indicated that long non-coding RNAs(lncRNAs)play critical roles in the development and progression of cancers,including esophageal squamous cell carcinoma(ESCC).However,the mechanisms of lncR...Accumulating evidence has indicated that long non-coding RNAs(lncRNAs)play critical roles in the development and progression of cancers,including esophageal squamous cell carcinoma(ESCC).However,the mechanisms of lncRNAs in ESCC are still incompletely understood and therapeutic attempts for in vivo targeting cancer-associated lncRNA remain a challenge.By RNA-sequencing analysis,we identified that LLNLR-299G3.1 was a novel ESCC-associated lncRNA.LLNLR-299G3.1 was up-regulated in ESCC tissues and cells and promoted ESCC cell proliferation and invasion.Silencing of LLNLR-299G3.1 with ASO(antisense oligonucleotide)resulted in opposite effects.Mechanistically,LLNLR-299G3.1 bound to cancerassociated RNA binding proteins and regulated the expression of cancer-related genes,including OSM,TNFRSF4,HRH3,and SSTR3.ChIRP-seq(chromatin isolation by RNA purification and sequencing)revealed that these genes contained enriched chromatin binding sites for LLNLR-299G3.1.Rescue experiments confirmed that the effects of LLNLR-299G3.1 on ESCC cell proliferation were dependent on interaction with HRH3 and TNFRSF4.Therapeutically,intravenous delivery of placental chondroitin sulfate A binding peptide-coated nanoparticles containing antisense oligonucleotide(pICSA-BP-ANPs)strongly inhibited ESCC tumor growth and significantly improved animal survival in vivo.Overall,our results suggest that LLNLR-299G3.1 promotes ESCC malignancy through regulating gene-chromatin interactions and targeting ESCC by pICSA-BP-ANPs may be an effective strategy for the treatment of lncRNA-associated ESCC.展开更多
BACKGROUND Previous reports have focused on muscle mass as a prognostic factor in esophageal cancer.AIM To investigate how preoperative body type influences the prognosis of patients with esophageal squamous cell carc...BACKGROUND Previous reports have focused on muscle mass as a prognostic factor in esophageal cancer.AIM To investigate how preoperative body type influences the prognosis of patients with esophageal squamous cell carcinoma who underwent neoadjuvant chemotherapy(NAC)and surgery.METHODS The subjects were 131 patients with clinical stage Ⅱ/Ⅲ esophageal squamous cell carcinoma who underwent subtotal esophagectomy after NAC.Skeletal muscle mass and quality were calculated based on computed tomography images prior to NAC,and their statistical association with long-term outcomes was examined retrospectively in this case-control study.RESULTS The disease-free survival rates in the low psoas muscle mass index(PMI)group vs the high PMI group were 41.3%vs 58.8%(P=0.036),respectively.In the high intramuscular adipose tissue content(IMAC)group vs the low IMAC group,the disease-free survival rates were 28.5%vs 57.6%(P=0.021),respectively.The overall survival(OS)rates for the low PMI group vs the high PMI group were 41.3%vs 64.5%(P=0.008),respectively,and for the high IMAC group vs the low IMAC group,they were 29.9%vs 61.9%(P=0.024),respectively.Analysis of the OS rate revealed significant differences in patients aged 60 years or older(P=0.018),those with pT3 or above disease(P=0.021),or those with lymph node metastasis(P=0.006),aside from PMI and IMAC.Multivariate analysis demonstrated that pT3 or above hazard ratio(HR):1.966,95%confidence interval(CI):1.089-3.550,(P=0.025),lymph node metastasis(HR:2.154,95%CI:1.118-4.148,P=0.022),low PMI(HR:2.266,95%CI:1.282-4.006,P=0.005),and high IMAC(HR:2.089,95%CI:1.036-4.214,P=0.022)were significant prognostic factors for esophageal squamous cell carcinoma.CONCLUSIONSkeletal muscle mass and quality before NAC in patients with esophageal squamous cellcarcinoma are significant prognostic factors for postoperative OS.展开更多
BACKGROUND Toripalimab and anlotinib have shown good response in esophageal cancer,with high objective response rate and progression free survival.Thus,they have been approved as second-line or above-line therapy for ...BACKGROUND Toripalimab and anlotinib have shown good response in esophageal cancer,with high objective response rate and progression free survival.Thus,they have been approved as second-line or above-line therapy for advanced or unresectable esophageal carcinoma.Combination of these two drugs may have synergistic effects,but evidence of which is lacking.CASE SUMMARY Here,we report on a 73-year-old male,newly diagnosed with advanced esophageal squamous cell carcinoma(ESCC),who received a combination of toripalimab and anlotinib.Complete response was achieved after treatment for 3 mo and remission was maintained up to 14 mo.CONCLUSION The combination therapy of toripalimab and anlotinib is a promising treatment for unresectable ESCC and related clinical trials are warranted.展开更多
Objective: To analyze the relationship between TIGIT and clinical features of Esophageal Squamous Cell Carcinoma, we use transcriptomic data from the TCGA database, and to investigate the relationship between TIGIT an...Objective: To analyze the relationship between TIGIT and clinical features of Esophageal Squamous Cell Carcinoma, we use transcriptomic data from the TCGA database, and to investigate the relationship between TIGIT and the immune microenvironment of Esophageal Squamous Cell Carcinoma, to provide a basis for improving the treatment strategy and prognosis of patients with Esophageal Squamous Cell Carcinoma. Methods: RNA sequencing data and clinical data corresponding to cancer tissues were obtained from the TCGA database for Esophageal carcinoma, Esophageal Squamous Cell Carcinoma tissues, and paraneoplastic tissues;then we analyzed the differences in TIGIT expression in Esophageal carcinoma, Esophageal Squamous Cell Carcinoma, and normal esophageal tissues;then we analyzed the relationship between TIGIT expression levels and overall survival in Esophageal Squamous Cell Carcinoma;finally, we explored the relationship between TIGIT expression levels and overall survival in Esophageal Squamous Cell Carcinoma. We investigated the relationship between TIGIT and the tumor immune microenvironment of Esophageal Squamous Cell Carcinoma by tumor immune infiltration and functional enrichment analysis. Results: Our study revealed that TIGIT was highly expressed in Esophageal Squamous Cell Carcinoma, and patients with high TIGIT expression had worse overall survival. We also found a close relationship between TIGIT expression levels and the immune microenvironment of Esophageal Squamous Cell Carcinoma, with high TIGIT expression positively correlated with multiple immune cells. Conclusion: Our study demonstrates that TIGIT is associated with Esophageal Squamous Cell Carcinoma malignancy and is closely linked to the immune microenvironment. Furthermore, high expression of TIGIT often predicts poorer clinical features.展开更多
BACKGROUND Cancer detection is a global research focus,and novel,rapid,and label-free techniques are being developed for routine clinical practice.This has led to the development of new tools and techniques from the b...BACKGROUND Cancer detection is a global research focus,and novel,rapid,and label-free techniques are being developed for routine clinical practice.This has led to the development of new tools and techniques from the bench side to routine clinical practice.In this study,we present a method that uses Raman spectroscopy(RS)to detect cancer in unstained formalin-fixed,resected specimens of the esophagus and stomach.Our method can record a clear Raman-scattered light spectrum in these specimens,confirming that the Raman-scattered light spectrum changes because of the histological differences in the mucosal tissue.AIM To evaluate the use of Raman-scattered light spectrum for detecting endoscopically resected specimens of esophageal squamous cell carcinoma(SCC)and gastric adenocarcinoma(AC).METHODS We created a Raman device that is suitable for observing living tissues,and attempted to acquire Raman-scattered light spectra in endoscopically resected specimens of six esophageal tissues and 12 gastric tissues.We evaluated formalin-fixed tissues using this technique and captured shifts at multiple locations based on feasibility,ranging from six to 19 locations 200 microns apart in the vertical and horizontal directions.Furthermore,a correlation between the obtained Raman scattered light spectra and histopathological diagnosis was performed.RESULTS We successfully obtained Raman scattered light spectra from all six esophageal and 12 gastric specimens.After data capture,the tissue specimens were sent for histopathological analysis for further processing because RS is a label-free methodology that does not cause tissue destruction or alterations.Based on data analysis of molecular-level substrates,we established cut-off values for the diagnosis of esophageal SCC and gastric AC.By analyzing specific Raman shifts,we developed an algorithm to identify the range of esophageal SCC and gastric AC with an accuracy close to that of histopathological diagnoses.CONCLUSION Our technique provides qualitative information for real-time morphological diagnosis.However,further in vivo evaluations require an excitation light source with low human toxicity and large amounts of data for validation.展开更多
Esophageal cancer is one of the most fatal diseases worldwide mainly because of its rapid progression and poor prognosis.Although the incidence of esophageal adenocarcinoma has markedly risen in North America and Euro...Esophageal cancer is one of the most fatal diseases worldwide mainly because of its rapid progression and poor prognosis.Although the incidence of esophageal adenocarcinoma has markedly risen in North America and Europe in the past several decades, esophageal squamous cell carcinoma is still the predominant subtype of esophageal cancer, especially in China. It accounts for more than 90% of all esophageal squamous cell carcinoma cases in China. Geographical differentiation is one of the most distinctive characteristics of esophageal cancer. The progression, risk factors, and prognosis of these two subtypes of esophageal cancer differ. This study reviews the epidemiology, etiology, and prevention of esophageal squamous cell carcinoma in China, thereby providing systematic references for policy-makers who will decide on issues of esophageal cancer prevention and control.展开更多
Background: Concurrent chemoradiotherapy(CCRT) significantly increases the survival rate of esophageal squa?mous cell carcinoma(ESCC) patients with malignant fistulae. Recent clinical evidence has shown the benefits o...Background: Concurrent chemoradiotherapy(CCRT) significantly increases the survival rate of esophageal squa?mous cell carcinoma(ESCC) patients with malignant fistulae. Recent clinical evidence has shown the benefits of enteral nutrition for malnourished cancer patients. In this study, we aimed to validate that, with the support of enteral nutrition, ESCC patients who develop malignant fistulae might be able to complete CCRT and achieve long?term survival.Methods: We reviewed the medical records of 652 patients with ESCC who received definitive CCRT at Sun Yat?sen University Cancer Center between January 2010 and December 2012. Treatment outcome and toxicity were ret?rospectively evaluated in 40 ESCC patients with malignant fistulae. All the 40 patients were treated with CCRT and evaluated by clinical nutritionists using nutrition risk screening(NRS) before, during, and after treatment. Twenty?two patients received a nasogastric tube, and 18 underwent percutaneous endoscopic gastrostomy feeding. The median energy intake was 2166 kcal/day. Treatment response was evaluated at 3 months after the completion of CCRT.Results: With a median follow?up of 18 months(range, 3–39 months), patients' 1?year overall survival(OS) rate was 62.5%, and the estimated OS time was 25.5 months. Univariate analysis showed that the NRS score(P n NRS score(P se to treatment(P < 0.001) were sig= 0.003), increase i= 0.024), fistula closure(P = 0.011), and responnifi?cantly associated with OS. Multivariate analysis showed that tumor response(P = 0.044) and increase in NRS score(P = 0.044) were independent predictors of OS. Grade 3 vomiting was observed in 8 patients(20.0%), grade 3 neutro?penia was observed in 11 patients(27.5%), and grade 3 cough was observed in 13 patients(32.5%); 2 patients(5.0%) died of massive bleeding during treatment.Conclusions: CCRT combined with enteral nutrition support is effective for ESCC patients with malignant fistulae. Patients have an increased potential to be cured, especially those who experience complete response and have an increase in NRS score. Careful observation and nutrition support are required for patients with advanced T?category ESCC who undergo CCRT.展开更多
Esophageal cancer is the eighth most common malignant tumor and the sixth leading cause of cancer-related death worldwide.Esophageal squamous cell carcinoma(ESCC)is the main histological type of esophageal cancer,and ...Esophageal cancer is the eighth most common malignant tumor and the sixth leading cause of cancer-related death worldwide.Esophageal squamous cell carcinoma(ESCC)is the main histological type of esophageal cancer,and accounts for 90%of all cancer cases.Despite the progress made in surgery,chemotherapy,and radiotherapy,the mortality rate from esophageal cancer remains high,and the overall 5-year survival rate is less than 20%,even in developed countries.The C-X-C motif chemokine ligand 12(CXCL12)is a member of the CXC chemokine subgroup,which is widely expressed in a variety of tissues and cells.CXCL12 participates in the regulation of many physiological and pathological processes by binding to its specific receptor,C-X-C motif chemokine receptor type 4(CXCR4),where it causes embryonic development,immune response,and angiogenesis.In addition,increasing evidence indicates that the CXCL12/CXCR4 axis plays an important role in the biological processes of tumor cells.Studies have shown that CXCL12 and its receptor,CXCR4,are highly expressed in ESCC.This abnormal expression contributes to tumor proliferation,lymph node and distant metastases,and worsening prognosis.At present,antagonists and imaging agents against CXCL12 or CXCR4 have been developed to interfere with the malignant process and monitor metastasis of tumors.This article summarizes the structure,function,and regulatory mechanism of CXCL12/CXCR4 and its role in the malignancy of ESCC.Current results from preclinical research targeting CXCL12/CXCR4 are also summarized to provide a reference for the clinical diagnosis and treatment of ESCC.展开更多
AIM: To study the expression of β-catenin in esophageal squamous cell carcinoma (ESCC) at stage T2-3N0M0 and its relation with the prognosis of ESCC patients. METHODS: Expression of β-catenin in 227 ESCC speci-mens ...AIM: To study the expression of β-catenin in esophageal squamous cell carcinoma (ESCC) at stage T2-3N0M0 and its relation with the prognosis of ESCC patients. METHODS: Expression of β-catenin in 227 ESCC speci-mens was detected by immunohistochemistry (IHC). A reproducible semi-quantitative method which takes both staining percentage and intensity into account was applied in IHC scoring, and receiver operating char-acteristic curve analysis was used to select the cut-off score for high or low IHC reactivity. Then, correlation of β-catenin expression with clinicopathological features and prognosis of ESCC patients was determined. RESULTS: No significant correlation was observed between β-catenin expression and clinicopathological parameters in terms of gender, age, tumor size, tumor grade, tumor location, depth of invasion and pathologi-cal stage. The Kaplan-Meier survival curve showed that the up-regulated expression of β-catenin indicated a poorer post-operative survival rate of ESCC patients at stage T2-3N0M0 (P = 0.004), especially of those with T3 lesions (P = 0.014) or with stage ⅡB diseases (P = 0.007). Multivariate analysis also confirmed that β-catenin was an independent prognostic factor for the overall survival rate of ESCC patients at stage T2-3N0M0 (relative risk = 1.642, 95% CI: 1.159-2.327, P = 0.005). CONCLUSION: Elevated β-catenin expression level may be an adverse indicator for the prognosis of ESCC patients at stage T2-3N0M0, especially for those with T3 lesions or stage ⅡB diseases.展开更多
Background: Insulin?like growth factor?binding protein?3(IGFBP?3) is suggested to predict the radiosensitivity and/or prognosis of patients with esophageal squamous cell carcinoma(ESCC). The present study was designed...Background: Insulin?like growth factor?binding protein?3(IGFBP?3) is suggested to predict the radiosensitivity and/or prognosis of patients with esophageal squamous cell carcinoma(ESCC). The present study was designed to investi?gate the clinical and prognostic efects of IGFBP?3 on ESCC.Methods: IGFBP?3 was detected by immunohistochemistry in parain?embedded tissues from 70 ESCC patients treated with radiotherapy alone and further examined by western blotting analysis in 10 pairs of fresh ESCC tissues and adjacent non?malignant esophageal specimens. Receiver operating characteristic(ROC) analysis was used to determine cut?of scores for tumor positivity and to evaluate patient survival status. The χ2 test was performed to analyze the association of IGFBP?3 expression with clinical characteristics and radiotherapy response. Associations between prognostic outcomes and IGFBP?3 expression were investigated using Kaplan–Meier analysis and the Cox proportional hazards model.Results: The threshold for IGFBP?3 positivity was set to greater than 65% [area under the ROC curve(AUC)(45.7%) were deined as having high IGFBP?3 expression= 0.690, P < 0.019]. Of the 70 ESCC patient tissues tested, 32. The levels of IGFBP?3 protein expression were decreased in 70.0%(7 of 10) of ESCC tissues compared with adjacent non?malignant esophageal tissue. In addition, IGFBP?3 expression was associated with pathologic classiication(P < 0.05 for T, N, and M categories and clinical stage). Patients with elevated protein level of IGFBP?3 in the tumor had an improved radiotherapy response and prolonged overall survival(P < 0.001).Conclusions: High level of IGFBP?3 expression in ESCC associates with early clinical stages and are predictive for favorable survival of the patients treated with radiotherapy.展开更多
AIM: To investigate the correlation between cyclooxygenase-2 (COX-2) and cell cycle-regulatory proteins in patients with esophageal squamous cell carcinoma (ESCC). METHODS: One hundred and two surgically obtained spec...AIM: To investigate the correlation between cyclooxygenase-2 (COX-2) and cell cycle-regulatory proteins in patients with esophageal squamous cell carcinoma (ESCC). METHODS: One hundred and two surgically obtained specimens of ESCC were randomly collected. All specimens were obtained from patients who had not received chemoor radiotherapy prior to surgical resection.Twenty-eight specimens of normal squamous epithelium served as controls. The expression of COX-2, Ki-67, cyclin A and p27 was examined by immunohistochemistry. The Pearson test was used to analyze the relationship between groups. RESULTS: The protein level of COX-2, Ki-67 and cyclin A was significantly higher in ESCC than in normal squamous epithelium (74.7±61.2 vs 30.2 ± 43.4, 64.0 ± 51.6 vs 11.6 ± 2.3, 44.2 ± 32.2 vs 11.7 ± 5.0, respectively, all P<0.01). In contrast, the protein level of p27 was signifi cantly lower in ESCC than in normal squamous epithelium (182.0 ±69.0 vs 266.4±28.0, P<0.01). In ESCC, COX-2 expression was correlated with T stage, the score of T1-T2 stage was lower than that of T3-T4 stage (55.0±42.3 vs 83.0 ± 66.5, P<0.05), and Ki-67, cyclin A and p27 expressions were correlated with the tumor differentiation (43.8±31.7 vs 98.4± 84.8, 32.0 ± 19.0 vs 54.1 ±53.7,206.2±61.5 vs 123.5±68.3, respectively, all P<0.01). COX-2 expression was positively correlated to Ki-67, cyclin A and negatively correlated to p27 expression in ESCC (r=0.270, 0.233 and-0.311, respectively, all P<0.05).CONCLUSION: The expression of COX-2 is correlated with tumor cell invasion and is closely related to the cell proliferation in patients with ESCC.展开更多
Objective: Esophageal squamous cell carcinoma(ESCC) is one of the dominant malignances worldwide, but currently there is less focus on the microbiota with ESCC and its precancerous lesions.Methods: Paired esophageal b...Objective: Esophageal squamous cell carcinoma(ESCC) is one of the dominant malignances worldwide, but currently there is less focus on the microbiota with ESCC and its precancerous lesions.Methods: Paired esophageal biopsy and swab specimens were obtained from 236 participants in Linzhou, China.Data from 16 S ribosomal RNA gene sequencing were processed using quantitative insights into microbial ecology(QIIME2) and R Studio to evaluate differences. The Wilcoxon rank sum test and Kruskal-Wallis rank sum test were used to compare diversity and characteristic genera by specimens and participant groups. Ordinal logistic regression model was used to build microbiol prediction model.Results: Microbial diversity was similar between biopsy and swab specimens, including operational taxonomic unit(OTU) numbers and Shannon index. There were variations and similarities of esophageal microbiota among different pathological characteristics of ESCC. Top 10 relative abundance genera in all groups include Streptococcus, Prevotella, Veillonella, Actinobacillus, Haemophilus, Neisseria, Alloprevotella, Rothia, Gemella and Porphyromonas. Genus Streptococcus, Haemophilus, Neisseria and Porphyromonas showed significantly difference in disease groups when compared to normal control, whereas Streptococcus showed an increasing tendency with the progression of ESCC and others showed a decreasing tendency. About models based on all combinations of characteristic genera, only taken Streptococcus and Neisseria into model, the prediction performance was the ideal one, of which the area under the curve(AUC) was 0.738.Conclusions: Esophageal biopsy and swab specimens could yield similar microbial characterization. The combination of Streptococcus and Neisseria has the potential to predict the progression of ESCC, which is needed to confirm by large-scale, prospective cohort studies.展开更多
BACKGROUND Non-magnifying endoscopy with narrow-band imaging(NM-NBI)has been frequently used in routine screening of esophagus squamous cell carcinoma(ESCC).The performance of NBI for screening of early ESCC is,howeve...BACKGROUND Non-magnifying endoscopy with narrow-band imaging(NM-NBI)has been frequently used in routine screening of esophagus squamous cell carcinoma(ESCC).The performance of NBI for screening of early ESCC is,however,significantly affected by operator experience.Artificial intelligence may be a unique approach to compensate for the lack of operator experience.AIM To construct a computer-aided detection(CAD)system for application in NMNBI to identify early ESCC and to compare it with our previously reported CAD system with endoscopic white-light imaging(WLI).METHODS A total of 2167 abnormal NM-NBI images of early ESCC and 2568 normal images were collected from three institutions(Zhongshan Hospital of Fudan University,Xuhui Hospital,and Kiang Wu Hospital)as the training dataset,and 316 pairs of images,each pair including images obtained by WLI and NBI(same part),were collected for validation.Twenty endoscopists participated in this study to review the validation images with or without the assistance of the CAD systems.The diagnostic results of the two CAD systems and improvement in diagnostic efficacy of endoscopists were compared in terms of sensitivity,specificity,accuracy,positive predictive value,and negative predictive value.RESULTS The area under receiver operating characteristic curve for CAD-NBI was 0.9761.For the validation dataset,the sensitivity,specificity,accuracy,positive predictive value,and negative predictive value of CAD-NBI were 91.0%,96.7%,94.3%,95.3%,and 93.6%,respectively,while those of CAD-WLI were 98.5%,83.1%,89.5%,80.8%,and 98.7%,respectively.CAD-NBI showed superior accuracy and specificity than CAD-WLI(P=0.028 and P≤0.001,respectively),while CAD-WLI had higher sensitivity than CAD-NBI(P=0.006).By using both CAD-WLI and CAD-NBI,the endoscopists could improve their diagnostic efficacy to the highest level,with accuracy,sensitivity,and specificity of 94.9%,92.4%,and 96.7%,respectively.CONCLUSION The CAD-NBI system for screening early ESCC has higher accuracy and specificity than CAD-WLI.Endoscopists can achieve the best diagnostic efficacy using both CAD-WLI and CAD-NBI.展开更多
基金Supported by Tianjin Key Medical Discipline(Specialty)Construction Project,No.TJYXZDXK-009ATianjin Medical University Cancer Hospital National Natural Science Foundation Cultivation Program,No.220108+3 种基金National Natural Science Foundation of China,No.82373134Science and Technology Development Fund of Tianjin Education Commission for Higher Education,No.2022KJ228Chinese Anti-Cancer Association-Heng Rui Anti-angiogenesis Targeted Tumor Research Fund,No.2021001045and Scientific Research Translational Foundation of Wenzhou Safety(Emergency)Institute of Tianjin University,No.TJUWYY2022025.
文摘BACKGROUND Esophageal squamous cell carcinoma(ESCC)is a deadly malignancy with limited treatment options.Deubiquitinases(DUBs)have been confirmed to play a crucial role in the development of malignant tumors.JOSD2 is a DUB involved in con-trolling protein deubiquitination and influencing critical cellular processes in cancer.AIM To investigate the impact of JOSD2 on the progression of ESCC.METHODS Bioinformatic analyses were employed to explore the expression,prognosis,and enriched pathways associated with JOSD2 in ESCC.Lentiviral transduction was utilized to manipulate JOSD2 expression in ESCC cell lines(KYSE30 and RESULTS )Preliminary research indicated that JOSD2 was highly expressed in ESCC tissues,which was associated with poor prognosis.Further analysis demonstrated that JOSD2 was upregulated in ESCC cell lines compared to normal esophageal cells.JOSD2 knockdown inhibited ESCC cell activity,including proliferation and colony-forming ability.Moreover,JOSD2 knockdown decreased the drug resistance and migration of ESCC cells,while JOSD2 overexpression enhanced these phenotypes.In vivo xenograft assays further confirmed that JOSD2 promoted tumor proliferation and drug resistance in ESCC.Mechanistically,JOSD2 appears to activate the MAPK/ERK and PI3K/AKT signaling pathways.Mass spectrometry was used to identify crucial substrate proteins that interact with JOSD2,which identified the four primary proteins that bind to JOSD2,namely USP47,IGKV2D-29,HSP90AB1,and PRMT5.CONCLUSION JOSD2 plays a crucial role in enhancing the proliferation,migration,and drug resistance of ESCC,suggesting that JOSD2 is a potential therapeutic target in ESCC.
文摘In recent years,endoscopic resection,particularly endoscopic submucosal dis-section,has become increasingly popular in treating non-metastatic superficial esophageal squamous cell carcinoma(ESCC).In this evolving paradigm,it is crucial to identify factors that predict higher rates of lymphatic invasion and poorer outcomes.Larger tumor size,deeper invasion,poorer differentiation,more infiltrative growth patterns(INF-c),higher-grade tumor budding,positive lymphovascular invasion,and certain biomarkers have been associated with lymph node metastasis and increased morbidity through retrospective reviews,leading to the construction of comprehensive nomograms for outcome prediction.If validated by future prospective studies,these nomograms would prove highly applicable in guiding the selection of treatment for superficial ESCC.
文摘Objective:To explore and analyze the expression and clinical significance of vascular endothelial growth factor(VEGF),hypoxia-inducible factor 1α(HIF-1α),and metabolic indicators in esophageal squamous cell carcinoma(ESCC).Methods:Sixty ESCC patients admitted to the hospital from October 2021 to October 2023 were selected as the ESCC group.Sixty normal healthy patients from the same period were chosen as the control group.Their serum samples and tissue samples were collected.Metabolic indicators of all study subjects were obtained based on the basic biochemical results upon admission.RT-PCR was utilized to detect the expression of VEGF and HIF-1αin ESCC tissues.Results:The expression of VEGF and HIF-1αin the ESCC T3+T4 group was significantly higher than that of the carcinoma in situ(Tis)group,T1+T2 group,and control group.Furthermore,the expression of HIF-1αwas found to be related to the expression of VEGF,showing a significant correlation between the quantities.Significant differences in the levels of metabolic indicators were observed between the ESCC group and the control group(P<0.05).Conclusion:Metabolic indicators are associated with the onset of ESCC in patients.Abnormal lipid metabolism plays a crucial role in the occurrence and development of tumors.The expression of VEGF and HIF-1αin ESCC tissues significantly correlates with the tumor stage,providing a new reference for the diagnosis and treatment of ESCC.
基金the National Natural Science Foundation of China,No.82173253the Sichuan Province Science and Technology Support Program,No.2022YFH0003 and No.2023NSFSC1900+1 种基金the Postdoctoral Research Foundation of West China Hospital,No.2021HXBH020and the Medico-Engineering Cooperation Funds from the University of Electronic Science and Technology of China and West China Hospital of Sichuan University,No.HXDZ22005.
文摘BACKGROUND Superficial esophageal squamous cell carcinoma(ESCC)is defined as cancer infiltrating the mucosa and submucosa,regardless of regional lymph node metastasis(LNM).Endoscopic resection of superficial ESCC is suitable for lesions that have no or low risk of LNM.Patients with a high risk of LNM always need further treatment after endoscopic resection.Therefore,accurately assessing the risk of LNM is critical for additional treatment options.AIM To analyze risk factors for LNM and develop a nomogram to predict LNM risk in superficial ESCC patients.METHODS Clinical and pathological data of superficial ESCC patients undergoing esophagectomy from January 1,2009 to January 31,2016 were collected.Logistic regression analysis was used to predict LNM risk factors,and a nomogram was developed based on risk factors derived from multivariate logistic regression analysis.The receiver operating characteristic(ROC)curve was used to obtain the accuracy of the nomogram model.RESULTSA total of 4660 patients with esophageal cancer underwent esophagectomy.Of these,474 superficial ESCC patientswere enrolled in the final analysis,with 322 patients in the training set and 142 patients in the validation set.Theprevalence of LNM was 3.29%(5/152)for intramucosal cancer and increased to 26.40%(85/322)for submucosalcancer.Multivariate logistic analysis showed that tumor size,invasive depth,tumor differentiation,infiltrativegrowth pattern,tumor budding,and lymphovascular invasion were significantly correlated with LNM.Anomogram using these six variables showed good discrimination with an area under the ROC curve of 0.789(95%CI:0.737-0.841)in the training set and 0.827(95%CI:0.755-0.899)in the validation set.CONCLUSIONWe developed a useful nomogram model to predict LNM risk for superficial ESCC patients which will facilitateadditional decision-making in treating patients who undergo endoscopic resection.
文摘Esophageal cancer(EC)ranks among the most prevalent malignant tumors affecting the digestive tract.Esophageal squamous cell carcinoma(ESCC)stands as the prevailing pathological subtype,encompassing approximately 90%of all EC patients.In clinical stage II-IVA locally advanced ESCC cases,the primary approach to treatment involves a combination of neoadjuvant therapy and surgical resection.Despite concerted efforts,the long-term outcomes for ESCC patients remain unsatisfactory,with dismal prognoses.However,recent years have witnessed remarkable strides in immunotherapy,particularly in the secondand first-line treatment of advanced or metastatic ESCC,with the development of monoclonal antibodies that inhibit programmed death 1 or programmed death ligand 1 demonstrating encouraging responses and perioperative clinical benefits for various malignancies,including ESCC.This comprehensive review aims to present the current landscape of perioperative immunotherapy for resectable ESCC,focusing specifically on the role of immune checkpoint inhibitors during the perioperative period.Additionally,the review will explore promising biomarkers and offer insights into future prospects.
基金funded by the Department of Education of Yunnan Province(No.2021J0244).
文摘Esophageal squamous cell carcinoma(ESCC)is among the most prevalent causes of cancer-related death in patients worldwide.Resistance to immunotherapy and chemotherapy results in worse survival outcomes in ESCC.It is urgent to explore the underlying molecular mechanism of immune evasion and chemoresistance in ESCC.Here,we conducted RNA-sequencing analysis in ten ESCC tissues from cisplatin-based neoadjuvant chemotherapy patients.We found that DMRTA1 was extremely upregulated in the non-pathologic complete response(non-pCR)group.The proliferation rate of esophageal squamous carcinoma cells was markedly decreased after knockdown of DMRTA1 expression,which could increase cisplatin sensitivity in ESCC.Additionally,suppression of DMRTA1 could decrease the immune escape of esophageal squamous carcinoma cells.Further mechanistic studies suggest that DMRTA1 can promote its expression by binding to the promoter of SOX2,which plays important roles in the progression and chemoresistance of ESCC in the form of positive feedback.Therefore,DMRTA1 could be a potential target to suppress immune escape and overcome chemoresistance in ESCC.
文摘BACKGROUND Esophageal squamous cell carcinoma(ESCC)is causing a high mortality rate due to the lack of efficient early prognosis markers and suitable therapeutic regimens.The prognostic role of genes responsible for the acquisition of radioresistance in ESCC has not been fully elucidated.AIM To establish a prognostic model by studying gene expression patterns pertinent to radioresistance in ESCC patients.METHODS Datasets were obtained from the Gene Expression Omnibus and The Cancer Genome Atlas databases.The edgeR,a Bioconductor package,was used to analyze mRNA expression between different groups.We screened genes specifically responsible for radioresistance to estimate overall survival.Pearson correlation analysis was performed to confirm whether the expression of those genes correlated with each other.Genes contributing to radioresistance and overall survival were assessed by the multivariate Cox regression model through the calculation ofβi and risk score using the following formula:∑^(n)_(i=1)βi×PSI.RESULTS We identified three prognostic mRNAs(cathepsin S[CTSS],cluster of differentiation 180[CD180],and SLP adapter and CSK-interacting membrane protein[SCIMP])indicative of radioresistance.The expression of the three identified mRNAs was related to each other(r>0.70 and P<0.05).As to 1-year and 3-year overall survival prediction,the area under the time-dependent receiver operating characteristic curve of the signature consisting of the three mRNAs was 0.716 and 0.841,respectively.When stratifying patients based on the risk score derived from the signature,the high-risk group exhibited a higher death risk and shorter survival time than the low-risk group(P<0.0001).Overall survival of the low-risk patients was significantly better than that of the highrisk patients(P=0.018).CONCLUSION We have developed a novel three-gene prognostic signature consisting of CTSS,CD180,and SCIMO for ESCC,which may facilitate the prediction of early prognosis of this malignancy.
基金This study was approved by the Medical Ethics Committee of Shenzhen University Health Science Center(protocol no.2016001).
文摘Accumulating evidence has indicated that long non-coding RNAs(lncRNAs)play critical roles in the development and progression of cancers,including esophageal squamous cell carcinoma(ESCC).However,the mechanisms of lncRNAs in ESCC are still incompletely understood and therapeutic attempts for in vivo targeting cancer-associated lncRNA remain a challenge.By RNA-sequencing analysis,we identified that LLNLR-299G3.1 was a novel ESCC-associated lncRNA.LLNLR-299G3.1 was up-regulated in ESCC tissues and cells and promoted ESCC cell proliferation and invasion.Silencing of LLNLR-299G3.1 with ASO(antisense oligonucleotide)resulted in opposite effects.Mechanistically,LLNLR-299G3.1 bound to cancerassociated RNA binding proteins and regulated the expression of cancer-related genes,including OSM,TNFRSF4,HRH3,and SSTR3.ChIRP-seq(chromatin isolation by RNA purification and sequencing)revealed that these genes contained enriched chromatin binding sites for LLNLR-299G3.1.Rescue experiments confirmed that the effects of LLNLR-299G3.1 on ESCC cell proliferation were dependent on interaction with HRH3 and TNFRSF4.Therapeutically,intravenous delivery of placental chondroitin sulfate A binding peptide-coated nanoparticles containing antisense oligonucleotide(pICSA-BP-ANPs)strongly inhibited ESCC tumor growth and significantly improved animal survival in vivo.Overall,our results suggest that LLNLR-299G3.1 promotes ESCC malignancy through regulating gene-chromatin interactions and targeting ESCC by pICSA-BP-ANPs may be an effective strategy for the treatment of lncRNA-associated ESCC.
文摘BACKGROUND Previous reports have focused on muscle mass as a prognostic factor in esophageal cancer.AIM To investigate how preoperative body type influences the prognosis of patients with esophageal squamous cell carcinoma who underwent neoadjuvant chemotherapy(NAC)and surgery.METHODS The subjects were 131 patients with clinical stage Ⅱ/Ⅲ esophageal squamous cell carcinoma who underwent subtotal esophagectomy after NAC.Skeletal muscle mass and quality were calculated based on computed tomography images prior to NAC,and their statistical association with long-term outcomes was examined retrospectively in this case-control study.RESULTS The disease-free survival rates in the low psoas muscle mass index(PMI)group vs the high PMI group were 41.3%vs 58.8%(P=0.036),respectively.In the high intramuscular adipose tissue content(IMAC)group vs the low IMAC group,the disease-free survival rates were 28.5%vs 57.6%(P=0.021),respectively.The overall survival(OS)rates for the low PMI group vs the high PMI group were 41.3%vs 64.5%(P=0.008),respectively,and for the high IMAC group vs the low IMAC group,they were 29.9%vs 61.9%(P=0.024),respectively.Analysis of the OS rate revealed significant differences in patients aged 60 years or older(P=0.018),those with pT3 or above disease(P=0.021),or those with lymph node metastasis(P=0.006),aside from PMI and IMAC.Multivariate analysis demonstrated that pT3 or above hazard ratio(HR):1.966,95%confidence interval(CI):1.089-3.550,(P=0.025),lymph node metastasis(HR:2.154,95%CI:1.118-4.148,P=0.022),low PMI(HR:2.266,95%CI:1.282-4.006,P=0.005),and high IMAC(HR:2.089,95%CI:1.036-4.214,P=0.022)were significant prognostic factors for esophageal squamous cell carcinoma.CONCLUSIONSkeletal muscle mass and quality before NAC in patients with esophageal squamous cellcarcinoma are significant prognostic factors for postoperative OS.
文摘BACKGROUND Toripalimab and anlotinib have shown good response in esophageal cancer,with high objective response rate and progression free survival.Thus,they have been approved as second-line or above-line therapy for advanced or unresectable esophageal carcinoma.Combination of these two drugs may have synergistic effects,but evidence of which is lacking.CASE SUMMARY Here,we report on a 73-year-old male,newly diagnosed with advanced esophageal squamous cell carcinoma(ESCC),who received a combination of toripalimab and anlotinib.Complete response was achieved after treatment for 3 mo and remission was maintained up to 14 mo.CONCLUSION The combination therapy of toripalimab and anlotinib is a promising treatment for unresectable ESCC and related clinical trials are warranted.
文摘Objective: To analyze the relationship between TIGIT and clinical features of Esophageal Squamous Cell Carcinoma, we use transcriptomic data from the TCGA database, and to investigate the relationship between TIGIT and the immune microenvironment of Esophageal Squamous Cell Carcinoma, to provide a basis for improving the treatment strategy and prognosis of patients with Esophageal Squamous Cell Carcinoma. Methods: RNA sequencing data and clinical data corresponding to cancer tissues were obtained from the TCGA database for Esophageal carcinoma, Esophageal Squamous Cell Carcinoma tissues, and paraneoplastic tissues;then we analyzed the differences in TIGIT expression in Esophageal carcinoma, Esophageal Squamous Cell Carcinoma, and normal esophageal tissues;then we analyzed the relationship between TIGIT expression levels and overall survival in Esophageal Squamous Cell Carcinoma;finally, we explored the relationship between TIGIT expression levels and overall survival in Esophageal Squamous Cell Carcinoma. We investigated the relationship between TIGIT and the tumor immune microenvironment of Esophageal Squamous Cell Carcinoma by tumor immune infiltration and functional enrichment analysis. Results: Our study revealed that TIGIT was highly expressed in Esophageal Squamous Cell Carcinoma, and patients with high TIGIT expression had worse overall survival. We also found a close relationship between TIGIT expression levels and the immune microenvironment of Esophageal Squamous Cell Carcinoma, with high TIGIT expression positively correlated with multiple immune cells. Conclusion: Our study demonstrates that TIGIT is associated with Esophageal Squamous Cell Carcinoma malignancy and is closely linked to the immune microenvironment. Furthermore, high expression of TIGIT often predicts poorer clinical features.
基金Supported by MEXT KAKENHI,JP17K09022 and JP20K07643.
文摘BACKGROUND Cancer detection is a global research focus,and novel,rapid,and label-free techniques are being developed for routine clinical practice.This has led to the development of new tools and techniques from the bench side to routine clinical practice.In this study,we present a method that uses Raman spectroscopy(RS)to detect cancer in unstained formalin-fixed,resected specimens of the esophagus and stomach.Our method can record a clear Raman-scattered light spectrum in these specimens,confirming that the Raman-scattered light spectrum changes because of the histological differences in the mucosal tissue.AIM To evaluate the use of Raman-scattered light spectrum for detecting endoscopically resected specimens of esophageal squamous cell carcinoma(SCC)and gastric adenocarcinoma(AC).METHODS We created a Raman device that is suitable for observing living tissues,and attempted to acquire Raman-scattered light spectra in endoscopically resected specimens of six esophageal tissues and 12 gastric tissues.We evaluated formalin-fixed tissues using this technique and captured shifts at multiple locations based on feasibility,ranging from six to 19 locations 200 microns apart in the vertical and horizontal directions.Furthermore,a correlation between the obtained Raman scattered light spectra and histopathological diagnosis was performed.RESULTS We successfully obtained Raman scattered light spectra from all six esophageal and 12 gastric specimens.After data capture,the tissue specimens were sent for histopathological analysis for further processing because RS is a label-free methodology that does not cause tissue destruction or alterations.Based on data analysis of molecular-level substrates,we established cut-off values for the diagnosis of esophageal SCC and gastric AC.By analyzing specific Raman shifts,we developed an algorithm to identify the range of esophageal SCC and gastric AC with an accuracy close to that of histopathological diagnoses.CONCLUSION Our technique provides qualitative information for real-time morphological diagnosis.However,further in vivo evaluations require an excitation light source with low human toxicity and large amounts of data for validation.
文摘Esophageal cancer is one of the most fatal diseases worldwide mainly because of its rapid progression and poor prognosis.Although the incidence of esophageal adenocarcinoma has markedly risen in North America and Europe in the past several decades, esophageal squamous cell carcinoma is still the predominant subtype of esophageal cancer, especially in China. It accounts for more than 90% of all esophageal squamous cell carcinoma cases in China. Geographical differentiation is one of the most distinctive characteristics of esophageal cancer. The progression, risk factors, and prognosis of these two subtypes of esophageal cancer differ. This study reviews the epidemiology, etiology, and prevention of esophageal squamous cell carcinoma in China, thereby providing systematic references for policy-makers who will decide on issues of esophageal cancer prevention and control.
基金supported by funds from the Scientific Research Foundation for the Returned Overseas Chinese Scholars, State Education MinistryNational Nature Science Fund, Support Grant 81301932+2 种基金the grants from the University Cancer Foundation via the Sister Institution Network Fund at The University of Texas MD Anderson Cancer Center and, in part, by the National Institutes of Health through MD Anderson Cancer Center Support Grant (CA016672)as some of these studies were performed in the North Campus Flow Cytometry and Cellular Imaging Core (PI: Ronald A. De Pinho, MD)supported by the grant from the Scientific Research Foundation for the Returned Overseas Chinese Scholars, State Education Ministry, China
文摘Background: Concurrent chemoradiotherapy(CCRT) significantly increases the survival rate of esophageal squa?mous cell carcinoma(ESCC) patients with malignant fistulae. Recent clinical evidence has shown the benefits of enteral nutrition for malnourished cancer patients. In this study, we aimed to validate that, with the support of enteral nutrition, ESCC patients who develop malignant fistulae might be able to complete CCRT and achieve long?term survival.Methods: We reviewed the medical records of 652 patients with ESCC who received definitive CCRT at Sun Yat?sen University Cancer Center between January 2010 and December 2012. Treatment outcome and toxicity were ret?rospectively evaluated in 40 ESCC patients with malignant fistulae. All the 40 patients were treated with CCRT and evaluated by clinical nutritionists using nutrition risk screening(NRS) before, during, and after treatment. Twenty?two patients received a nasogastric tube, and 18 underwent percutaneous endoscopic gastrostomy feeding. The median energy intake was 2166 kcal/day. Treatment response was evaluated at 3 months after the completion of CCRT.Results: With a median follow?up of 18 months(range, 3–39 months), patients' 1?year overall survival(OS) rate was 62.5%, and the estimated OS time was 25.5 months. Univariate analysis showed that the NRS score(P n NRS score(P se to treatment(P < 0.001) were sig= 0.003), increase i= 0.024), fistula closure(P = 0.011), and responnifi?cantly associated with OS. Multivariate analysis showed that tumor response(P = 0.044) and increase in NRS score(P = 0.044) were independent predictors of OS. Grade 3 vomiting was observed in 8 patients(20.0%), grade 3 neutro?penia was observed in 11 patients(27.5%), and grade 3 cough was observed in 13 patients(32.5%); 2 patients(5.0%) died of massive bleeding during treatment.Conclusions: CCRT combined with enteral nutrition support is effective for ESCC patients with malignant fistulae. Patients have an increased potential to be cured, especially those who experience complete response and have an increase in NRS score. Careful observation and nutrition support are required for patients with advanced T?category ESCC who undergo CCRT.
基金supported by the National Natural Science Foundation of China(Grant Nos.81772619 and 81702405)Wu Jieping Medical Foundation(Grant No.320.6750.17519)+1 种基金Bethune Charitable Foundation(Grant No.HZB-20190528-18)Tianjin Natural Science Foundation for Youth(Grant No.19JCQNJC10800)。
文摘Esophageal cancer is the eighth most common malignant tumor and the sixth leading cause of cancer-related death worldwide.Esophageal squamous cell carcinoma(ESCC)is the main histological type of esophageal cancer,and accounts for 90%of all cancer cases.Despite the progress made in surgery,chemotherapy,and radiotherapy,the mortality rate from esophageal cancer remains high,and the overall 5-year survival rate is less than 20%,even in developed countries.The C-X-C motif chemokine ligand 12(CXCL12)is a member of the CXC chemokine subgroup,which is widely expressed in a variety of tissues and cells.CXCL12 participates in the regulation of many physiological and pathological processes by binding to its specific receptor,C-X-C motif chemokine receptor type 4(CXCR4),where it causes embryonic development,immune response,and angiogenesis.In addition,increasing evidence indicates that the CXCL12/CXCR4 axis plays an important role in the biological processes of tumor cells.Studies have shown that CXCL12 and its receptor,CXCR4,are highly expressed in ESCC.This abnormal expression contributes to tumor proliferation,lymph node and distant metastases,and worsening prognosis.At present,antagonists and imaging agents against CXCL12 or CXCR4 have been developed to interfere with the malignant process and monitor metastasis of tumors.This article summarizes the structure,function,and regulatory mechanism of CXCL12/CXCR4 and its role in the malignancy of ESCC.Current results from preclinical research targeting CXCL12/CXCR4 are also summarized to provide a reference for the clinical diagnosis and treatment of ESCC.
文摘AIM: To study the expression of β-catenin in esophageal squamous cell carcinoma (ESCC) at stage T2-3N0M0 and its relation with the prognosis of ESCC patients. METHODS: Expression of β-catenin in 227 ESCC speci-mens was detected by immunohistochemistry (IHC). A reproducible semi-quantitative method which takes both staining percentage and intensity into account was applied in IHC scoring, and receiver operating char-acteristic curve analysis was used to select the cut-off score for high or low IHC reactivity. Then, correlation of β-catenin expression with clinicopathological features and prognosis of ESCC patients was determined. RESULTS: No significant correlation was observed between β-catenin expression and clinicopathological parameters in terms of gender, age, tumor size, tumor grade, tumor location, depth of invasion and pathologi-cal stage. The Kaplan-Meier survival curve showed that the up-regulated expression of β-catenin indicated a poorer post-operative survival rate of ESCC patients at stage T2-3N0M0 (P = 0.004), especially of those with T3 lesions (P = 0.014) or with stage ⅡB diseases (P = 0.007). Multivariate analysis also confirmed that β-catenin was an independent prognostic factor for the overall survival rate of ESCC patients at stage T2-3N0M0 (relative risk = 1.642, 95% CI: 1.159-2.327, P = 0.005). CONCLUSION: Elevated β-catenin expression level may be an adverse indicator for the prognosis of ESCC patients at stage T2-3N0M0, especially for those with T3 lesions or stage ⅡB diseases.
基金supported by a Grant from the National Natural Science Foundation of China (NSFC 81272487)the Foundation of Guangdong Esophageal Cancer Research Institute (M201415)
文摘Background: Insulin?like growth factor?binding protein?3(IGFBP?3) is suggested to predict the radiosensitivity and/or prognosis of patients with esophageal squamous cell carcinoma(ESCC). The present study was designed to investi?gate the clinical and prognostic efects of IGFBP?3 on ESCC.Methods: IGFBP?3 was detected by immunohistochemistry in parain?embedded tissues from 70 ESCC patients treated with radiotherapy alone and further examined by western blotting analysis in 10 pairs of fresh ESCC tissues and adjacent non?malignant esophageal specimens. Receiver operating characteristic(ROC) analysis was used to determine cut?of scores for tumor positivity and to evaluate patient survival status. The χ2 test was performed to analyze the association of IGFBP?3 expression with clinical characteristics and radiotherapy response. Associations between prognostic outcomes and IGFBP?3 expression were investigated using Kaplan–Meier analysis and the Cox proportional hazards model.Results: The threshold for IGFBP?3 positivity was set to greater than 65% [area under the ROC curve(AUC)(45.7%) were deined as having high IGFBP?3 expression= 0.690, P < 0.019]. Of the 70 ESCC patient tissues tested, 32. The levels of IGFBP?3 protein expression were decreased in 70.0%(7 of 10) of ESCC tissues compared with adjacent non?malignant esophageal tissue. In addition, IGFBP?3 expression was associated with pathologic classiication(P < 0.05 for T, N, and M categories and clinical stage). Patients with elevated protein level of IGFBP?3 in the tumor had an improved radiotherapy response and prolonged overall survival(P < 0.001).Conclusions: High level of IGFBP?3 expression in ESCC associates with early clinical stages and are predictive for favorable survival of the patients treated with radiotherapy.
基金Supported by The "333 Plan" Fund of Jiangsu Province, China, No. 2009-24
文摘AIM: To investigate the correlation between cyclooxygenase-2 (COX-2) and cell cycle-regulatory proteins in patients with esophageal squamous cell carcinoma (ESCC). METHODS: One hundred and two surgically obtained specimens of ESCC were randomly collected. All specimens were obtained from patients who had not received chemoor radiotherapy prior to surgical resection.Twenty-eight specimens of normal squamous epithelium served as controls. The expression of COX-2, Ki-67, cyclin A and p27 was examined by immunohistochemistry. The Pearson test was used to analyze the relationship between groups. RESULTS: The protein level of COX-2, Ki-67 and cyclin A was significantly higher in ESCC than in normal squamous epithelium (74.7±61.2 vs 30.2 ± 43.4, 64.0 ± 51.6 vs 11.6 ± 2.3, 44.2 ± 32.2 vs 11.7 ± 5.0, respectively, all P<0.01). In contrast, the protein level of p27 was signifi cantly lower in ESCC than in normal squamous epithelium (182.0 ±69.0 vs 266.4±28.0, P<0.01). In ESCC, COX-2 expression was correlated with T stage, the score of T1-T2 stage was lower than that of T3-T4 stage (55.0±42.3 vs 83.0 ± 66.5, P<0.05), and Ki-67, cyclin A and p27 expressions were correlated with the tumor differentiation (43.8±31.7 vs 98.4± 84.8, 32.0 ± 19.0 vs 54.1 ±53.7,206.2±61.5 vs 123.5±68.3, respectively, all P<0.01). COX-2 expression was positively correlated to Ki-67, cyclin A and negatively correlated to p27 expression in ESCC (r=0.270, 0.233 and-0.311, respectively, all P<0.05).CONCLUSION: The expression of COX-2 is correlated with tumor cell invasion and is closely related to the cell proliferation in patients with ESCC.
基金the National Natural Science Foundation of China (No.81974493)the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences (No.2016-I2M-3-001)。
文摘Objective: Esophageal squamous cell carcinoma(ESCC) is one of the dominant malignances worldwide, but currently there is less focus on the microbiota with ESCC and its precancerous lesions.Methods: Paired esophageal biopsy and swab specimens were obtained from 236 participants in Linzhou, China.Data from 16 S ribosomal RNA gene sequencing were processed using quantitative insights into microbial ecology(QIIME2) and R Studio to evaluate differences. The Wilcoxon rank sum test and Kruskal-Wallis rank sum test were used to compare diversity and characteristic genera by specimens and participant groups. Ordinal logistic regression model was used to build microbiol prediction model.Results: Microbial diversity was similar between biopsy and swab specimens, including operational taxonomic unit(OTU) numbers and Shannon index. There were variations and similarities of esophageal microbiota among different pathological characteristics of ESCC. Top 10 relative abundance genera in all groups include Streptococcus, Prevotella, Veillonella, Actinobacillus, Haemophilus, Neisseria, Alloprevotella, Rothia, Gemella and Porphyromonas. Genus Streptococcus, Haemophilus, Neisseria and Porphyromonas showed significantly difference in disease groups when compared to normal control, whereas Streptococcus showed an increasing tendency with the progression of ESCC and others showed a decreasing tendency. About models based on all combinations of characteristic genera, only taken Streptococcus and Neisseria into model, the prediction performance was the ideal one, of which the area under the curve(AUC) was 0.738.Conclusions: Esophageal biopsy and swab specimens could yield similar microbial characterization. The combination of Streptococcus and Neisseria has the potential to predict the progression of ESCC, which is needed to confirm by large-scale, prospective cohort studies.
基金Supported by National Key R&D Program of China,No.2018YFC1315000,No.2018YFC1315005,No.2019YFC1315800,and No.2019YFC1315802National Natural Science Foundation of China,No.81861168036 and No.81702305+2 种基金Science and Technology Commission Foundation of Shanghai Municipality,No.19411951600,and No.19411951601Macao SAR Science and Technology Development Foundation,No.0023/2018/AFJDawn Program of Shanghai Education Commission,No.18SG08.
文摘BACKGROUND Non-magnifying endoscopy with narrow-band imaging(NM-NBI)has been frequently used in routine screening of esophagus squamous cell carcinoma(ESCC).The performance of NBI for screening of early ESCC is,however,significantly affected by operator experience.Artificial intelligence may be a unique approach to compensate for the lack of operator experience.AIM To construct a computer-aided detection(CAD)system for application in NMNBI to identify early ESCC and to compare it with our previously reported CAD system with endoscopic white-light imaging(WLI).METHODS A total of 2167 abnormal NM-NBI images of early ESCC and 2568 normal images were collected from three institutions(Zhongshan Hospital of Fudan University,Xuhui Hospital,and Kiang Wu Hospital)as the training dataset,and 316 pairs of images,each pair including images obtained by WLI and NBI(same part),were collected for validation.Twenty endoscopists participated in this study to review the validation images with or without the assistance of the CAD systems.The diagnostic results of the two CAD systems and improvement in diagnostic efficacy of endoscopists were compared in terms of sensitivity,specificity,accuracy,positive predictive value,and negative predictive value.RESULTS The area under receiver operating characteristic curve for CAD-NBI was 0.9761.For the validation dataset,the sensitivity,specificity,accuracy,positive predictive value,and negative predictive value of CAD-NBI were 91.0%,96.7%,94.3%,95.3%,and 93.6%,respectively,while those of CAD-WLI were 98.5%,83.1%,89.5%,80.8%,and 98.7%,respectively.CAD-NBI showed superior accuracy and specificity than CAD-WLI(P=0.028 and P≤0.001,respectively),while CAD-WLI had higher sensitivity than CAD-NBI(P=0.006).By using both CAD-WLI and CAD-NBI,the endoscopists could improve their diagnostic efficacy to the highest level,with accuracy,sensitivity,and specificity of 94.9%,92.4%,and 96.7%,respectively.CONCLUSION The CAD-NBI system for screening early ESCC has higher accuracy and specificity than CAD-WLI.Endoscopists can achieve the best diagnostic efficacy using both CAD-WLI and CAD-NBI.
