Establishment and evaluation of risk prediction model for the esophageal cancer via whole transcriptome analysis / 中国胸心血管外科临床杂志

@#Objective    To establish the gene-based esophageal cancer (ESCA) risk score prediction models via whole transcriptome analysis to provide ideas and basis for improving ESCA treatment strategies and patient prognosis. Methods    RNA sequencing data of esophageal squamous cell carcinoma (ESCC), esophageal adenocarcinoma (EAC) and adjacent tissues were obtained from The Cancer Genome Atlas database. The edgeR method was used to screen out the differential genes between ESCA tissue and normal tissue, and the key genes affecting the survival status of ESCC and EAC patients were initially identified through univariate Cox regression analysis. The least absolute shrinkage and selection operator regression analysis and multivariate Cox regression analysis were used to further screen genes and establish ESCC and EAC risk score prediction models. Results    The risk score prediction models were the independent prognostic factors for ESCA, and the risk score was significantly related to the survival status of patients. In ESCC, the risk score was related to T stage. In EAC, the risk score was related to lymph node metastasis, distant metastasis and clinical stage. The constructed nomogram based on risk score showed good predictive ability. In ESCC, the risk score was related to tumor immune cell infiltration and the expression of immune checkpoint genes. However, this feature was not obvious in EAC. Conclusion 聽 聽The ESCC and EAC risk score prediction models have shown good predictive capabilities, which provide certain inspiration and basis for optimizing the management of ESCA and improving the prognosis of patients.

Comparative genomic analysis of esophageal squamous cell carcinoma and adenocarcinoma: New opportunities towards molecularly targeted therapy

Esophageal cancer is one of the most lethal cancers worldwide because of its rapid progression and poor prognosis. Esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC) are two major subtypes of esophageal cancer. ESCC predominantly affects African and Asian populations, which is closely related to chronic smoking and alcohol consumption. EAC typically arises in Barrett's esophagus with a predilection for Western countries. While surgical operation and chemoradiotherapy have been applied to combat this deadly cancer, molecularly targeted therapy is still at the early stages. With the development of large-scale next-generation sequencing, various genomic alterations in ESCC and EAC have been revealed and their potential roles in the initiation and progression of esophageal cancer have been studied. Potential therapeutic targets have been identified and novel approaches have been developed to combat esophageal cancer. In this review, we comprehensively analyze the genomic alterations in EAC and ESCC and summarize the potential role of the genetic alterations in the development of esophageal cancer. Progresses in the therapeutics based on the different tissue types and molecular signatures have also been reviewed and discussed.

Low expression S100 calcium ion binding protein A6 promoting the proliferation and migration of esophageal adenocarcinoma SK-GT-4 cells / 解剖学报

Objective To explore the effect of S100 calcium ion binding protein A6 (S100A6) on proliferation and migration of esophageal adenocarcinoma SK-GT-4 cells. Methods Lenti viruses were used to construct stable transfected cell lines (shNC and shS100A6). Real-time PCR was used to detect the mRNA expression of S100A6. The inverted microscope and MTT were used to detect cell proliferation. The Transwell assay was used to detect cell migration. Western blotting was used to detect the expression of S100A6, p-ERK, p-Akt and its downstream molecular involved in proliferation and migration. Using U0126 ( inhibitor of MER1/2) and LY294002 ( inhibitor of PI3K) to detect the effect of these two inhibitors on cell proliferation and migration and the expression of p-ERK, p-Akt and its downstream molecular involved in proliferation and migration in shS100A6 cells. Results Stable cell lines of knockdown S100A6 were constructed. Knockdown S100A6 promoted cell proliferation and migration. Western blotting result displayed that in shS100A6 cells, the levels of p-Akt and p-ERK increased, p21 decreased, cyclinDl increased, and the expression of β-catenin and vimentin, increased. U0126 and LY294002 inhibited the migration of shS100A6 cells. U0126 had no effect on the proliferation of shS100A6 cells, however LY294002 could inhibit the proliferation of shS100A6 cells. U0126 treatment on shS100A6 cells could decrease p-ERK and β-catenin expression. After shS100A6 cells treated with LY294002, p-Akt and β-catenin expression decreased, p21 expression increased and the expression of cyclinDl decreased. Conclusion Low expression of S100A6 promotes cell proliferation and migration, which may be mediated by activation of p-Akt regulating cell cycle progression to promote cell proliferation and by activation of p-Akt/p-ERK to regulate β-catenin to promote cell migration.

Identification of key genes and pathways associated with esophageal adenocarcinoma development based on GEO database and bioinformatics / 西安交通大学学报(医学版)

【Objective】 To investigate the potential genes and pathways associated with esophageal adenocarcinoma through microarray expression profiling data analysis and bioinformatics approaches. 【Methods】 The mRNA expression microarray data related to esophageal adenocarcinoma development were screened out with GEO database, and the biological processes, signaling pathways and network of these genes were statistically analyzed using "R" software. 【Results】 The GSE26886 was obtained from GEO database. A total of 1383 differentially expressed genes were associated with carcinogenesis of esophageal adenocarcinoma, including 607 up-regulated and 776 down-regulated genes. These genes were involved in metabolism, stimulate responses, cell adhesion, cell regeneration and immune biological processes. Eight significantly enriched pathways were identified by pathway analysis. 【Conclusion】 The bioinformatic method can analyze the gene chip data effectively. Multiple genes and signaling pathways are involved in the carcinogenesis of esophageal adenocarcinoma, which provides a new idea or approach for exploring biomarkers of early screening and therapeutic targets.

Advances and challenges in the treatment of esophageal cancer

Esophageal cancer (EC) is one of the most common cancers with high morbidity and mortality rates. EC includes two histological subtypes, namely esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC). ESCC primarily occurs in East Asia, whereas EAC occurs in Western countries. The currently available treatment strategies for EC include surgery, chemotherapy, radiation therapy, molecular targeted therapy, and combinations thereof. However, the prognosis remains poor, and the overall five-year survival rate is very low. Therefore, achieving the goal of effective treatment remains challenging. In this review, we discuss the latest developments in chemotherapy and molecular targeted therapy for EC, and comprehensively analyze the application prospects and existing problems of immunotherapy. Collectively, this review aims to provide a better understanding of the currently available drugs through in-depth analysis, promote the development of new therapeutic agents, and eventually improve the treatment outcomes of patients with EC.

Research Progress on Related Genes of Gastroesophageal Reflux Disease / 胃肠病学

Gastroesophageal reflux disease (GERD) is a common disease with complex pathogenesis and poor efficacy of traditional treatments. With the development of molecular biotechnology, it is demonstrated that gene polymorphisms such as IL-1B, IL-1RN, PAR-2, and GSTP1 can increase disease susceptibility, while COX-2, CDX-2, MMPs, EGF and other genes can promote the development of GERD into Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC). The study of genetics will contribute to the prevention and treatment of the disease. This article reviewed the role of related genes in the occurrence, development and carcinogenesis of GERD.

Identification of key genes in esophageal adenocarcinoma and its clinical significance / 中国肿瘤生物治疗杂志

@#[Abstract] Objective: To screen the key genes associated with esophageal adenocarcinoma by using TCGA and GEO databases, and to analyze their biological functions, relevant signaling pathways and clinical significance. Methods: The esophageal adenocarcinoma data downloaded from TCGA database and GSE92396 microarray data from GEO database were integrated. The analysis of differentially expressed genes (DEGs) were performed by using DEseq2 and Limma packages of R software to obtain the co-differentially expressed genes, which were then chosen for the GO function enrichment analysis and KEGG pathway analysis with clusterProfiler package of R software. The key node genes that regulate the protein expressions in esophageal adenocarcinoma were screened out by protein-protein interaction (PPI) network analysis using the string website and Cytoscape 3.7.2 software. The correlation between key node genes and the survival of patients was further analyzed by combining with TCGA database. Results: By analyzing the chip data of 90 cases of adenocarcinoma tissues and 18 cases of normal esophageal tissues from databases, a total of 521 co-differentially expressed genes were obtained, including 356 upregulated genes and 165 downregulated genes. These genes were closely related to the metabolic-associated functions mainly involving epidermis development, epidermal cell differentiation and signaling pathways involving cytokine-cytokine receptor interaction, etc. The PPI network analysis revealed 15 key node genes. The survival time for patients with low CXCL8 and CCL20 expression was significantly longer compared with the patients with high expression level (median survival: 32.4 vs 19.7 months, P<0.05; 32.4 vs 13.9 months, P<0.05). Conclusion: These results show that CXCL8 and CCL20 may play an important role in the occurrence, development and prognosis of esophageal adenocarcinoma, and may be used as potential indicators to judge the prognosis of patients.

Caracterización clínico-patológica del cáncer esofágico avanzado en el Hospital Universitario Comandante Faustino Pérez. Matanzas / Clinic-pathologic characterization of the advanced esophagus cancer in the University Hospital Comandante Faustino Perez, Matanzas

RESUMEN Introducción: el cáncer de esófago en estadio avanzado, es uno de los más agresivos. En Cuba ocupa el décimo lugar entre las causas de muerte. Objetivo: caracterizar clínico y patológicamente a los pacientes con cáncer esofágico diagnosticados en el hospital estudiado. Materiales y métodos: se realizó un estudio prospectivo-descriptivo donde se efectuó una caracterización clínico-patológica a 59 pacientes con el diagnóstico endoscópico e histológico de cáncer de esófago, en el Hospital Faustino Pérez Hernández de Matanzas, de enero del 2016 a diciembre del 2017. Se estudiaron variables como: grupo etáreo, sexo, antecedentes patológicos personales y familiares, factores de riesgo, síntomas y signos predominantes en el diagnóstico, tiempo de aparición de los síntomas, tipo endoscópico, localización, tipo histológico, grado de diferenciación histológica, estadio de la enfermedad, tipo de tratamiento y tiempo de vida posterior al diagnóstico. Resultados: predominó el sexo masculino (88.1%) en pacientes mayores de 60 años (52.6%). La disfagia, la astenia y la anorexia fueron los síntomas más frecuentes; el etilismo crónico y el hábito de fumar fueron los factores de riesgo predominantes. La localización anatómica más frecuente fue el tercio medio (54.2%), el tipo endoscópico vegetante (88.1%) y el tipo histológico carcinoma epidermoide bien diferenciado (55.9%). Hubo relación entre el tiempo de inicio de los síntomas entre 3 y 6 meses antes del diagnóstico y el estadio IV de la enfermedad que predominó en 29 pacientes (49.2%). La mayoría de los pacientes recibieron tratamiento oncológico combinado con cirugía paliativa (47.5%) o ningún tratamiento (45.8%) pues el 50.8% de los pacientes fallecieron al mes del diagnóstico demostrando que el diagnóstico del cáncer esofágico se realiza casi siempre en estadios avanzados de la enfermedad cuando son posible pocas opciones terapéuticas. Conclusiones: el cáncer de esófago aún sigue diagnosticándose de forma tardía en estadios avanzados, con elevada prevalencia del carcinoma epidermoide sobre el adedocarcinoma que indica pocas acciones de salud preventivas sobre los factores de riesgo en la población estudiada, existiendo relación entre el estadio avanzado de la enfermedad y el poco tiempo de vida de estos pacientes posterior al diagnóstico.

ABSTRACT Introduction: the advanced-stage esophagus cancer is one of the most aggressive cancers. In Cuba, it is in the tenth place among the death reasons. Objective: to clinically and pathologically characterize the patients with esophageal cancer diagnosed in the mentioned hospital. Materials and methods: a prospective-descriptive study was carried out based on the clinical-histological characterization of 59 patients with the endoscopic and histological diagnosis of esophageal cancer in the Hospital "Faustino Pérez Hernández", of Matanzas, in the period from January 2016 to December 2017. The studied variables were: age group, sex, personal and familiar pathological antecedents, risk factors, symptoms and signs that were predominant in the diagnosis, time passed since the symptoms appeared, endoscopic kind, location, histological kind, level of histological differentiation, disease stage, kind of treatment, and life time after the diagnosis. Results: male sex predominated (88.1 %) in patients older than 60 years (52.6 %). Dysphagia, asthenia and anorexia were the most frequent signs. Alcoholism and smoking were the predominant risk factors. The most frequent anatomic location was the middle third (54.3 %); the endoscopic vegetating kind (88.1 %) and the histological kind well-differentiated epidermoid carcinoma (55.9 %) prevailed. The authors found a relation between the beginnings of the symptoms 3 to 6 months before the diagnosis and the disease IV stage predominating in 29 patients (49.2 %). Most of patients underwent oncologic treatment combined with palliative surgery (47.5 %) or no treatment (45.8 %), because 50.8 % of the patients died a month after the diagnosis, showing that the diagnosis of esophageal cancer is almost always achieved at advanced stages of the disease, when few therapeutic options are possible. Conclusions: esophageal cancer is still being diagnosed late, in advanced stages, with a higher prevalence of the epidermoid carcinoma over the adenocarcinoma. It indicates few health preventive actions on the risk factors among the studied population. There is a relation between the disease advanced stage and the few time patients live after the diagnosis.

Differentially expressed genes in esophageal squamous cell carcinoma and esophageal adenocarcinoma: A comprehensive analysis / 医学研究生学报

Objective This study aimed to analyze the differences in the molecular characteristics of transcriptome between esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC). Methods We obtained transcriptomic data on ESCC and EAC from the TCGA database, screened differentially expressed mRNAs, lncRNAs and miRNAs in cancer and the adjacent tissues, and constructed a network of ESCC- and EAC-related competitive endogenous RNA (ceRNA). We predicted the target genes and performed gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses on important miRNAs, and compared the molecular features of the transcriptomes between ESCC and EAC. Results The ceRNA network analysis showed that PVT1, LINC00524, miR-204, miR-383, HOXC8 and NTRK2 played important regulatory roles in both ESCC and EAC. Totally, 13 227 regulatory target genes were predicted with miR-204-5p via miRWalk and 232 target genes screened from the miRDB database. GO analysis revealed 38 enrichments, mainly involved in the regulation of cell-matrix adhesion, morphogenesis of cell membrane projection, and β-catenin combination, KEGG analysis showed 4 relevant pathways: the hedgehog, life-regulating, estrogen and relaxin signaling pathways, and survival analysis manifested LINC00261, MLIP-IT1 and LINC00504 as survival-related differentially expressed lncRNAs, hsa-mir-338 as differentially expressed miRNA, but no mRNA in ESCC. Survival-related differentially expressed lncRNAs in EAC included CYP1B1-AS1 and HOTAIR, and differentially expressed mRNAs included IL11, NTRK2, ANGPT2 and PBK. Of the differentially expressed lncRNAs in both ESCC and EAC, 150 (15.4%) were up-regulated and 158 (26.8%) down-regulated; of the miRNAs, 22 (24.2%) up-regulated and 8 (27.6%) down-regulated; and of the mRNAs, 234 (20.5%) up-regulated and 418 (23.7%) down-regulated. Conclusion There are significant molecular differences between ESCC and EAC, and the differentially expressed lncRNA, miRNA and mRNA may provide some new targets and molecular markers for the treatment and prognosis of esophageal carcinoma.

Role of goblet cells in the progression of Barrett′s esophagus / 中华消化杂志

Objective@#To investigate the clinical pathological features of Barrett′s esophagus in China, and to study the relationship between the number of goblet cells and the severity of Barrett′s esophageal dysplasia.@*Methods@#From January 2008 to October 2018, in the Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, the clinical and pathological data of 453 patients who underwent gastroscopy and pathologically diagnosed with Barrett′s esophagus were retrospectively analyzed. The clinical pathological features were compared between patients with goblet cells and patients without goblet cells. Periodic acid Schiff reaction (PAS) staining was performed on pathological slides of Barrett′s esophagus with goblet cells, and the relationship between the number of goblet cells, the number of positive crypts of goblet cells and the severity of Barrett′s esophageal dysplasia was analyzed. T test and chi-square test were performed for statistical analysis.@*Results@#Among 453 patients with Barrett′s esophagus, 251 (55.4%) were males and 202 (44.6%) were females. There were 218 Barrett′s esophagus with goblet cells, including 128 males (58.7%) and 90 females (41.3%). The average onset age was (60.6±11.9) years old, and the peak onset age was between 60 and 69 years old. The appearance under endoscopy mainly was circumferential type (58.2%, 127/218). There were 235 Barrett′s esophagus without goblet cells, 123 males (52.3%) and 112 females (47.7%). The average onset age was (56.1±14.4) years old, and the peak onset age was between 50 and 59 years old. The appearance under endoscopy was mainly circumferential type (40.0%, 94/235). The incidence of dysplasia in Barrett′s esophagus with goblet cells was higher than that without goblet cells (75.7%, 165/218 vs. 37.0%, 87/235), and the difference was statistically significant (χ2=68.501, P<0.01). PAS staining showed that goblet cells were stained purplish red. The number of goblet cells, total number of crypts, the number of positive crypts of goblet cells and the proportion of positive crypts of goblet cells of Barrett′s esophagus with mild dysplasia were all significantly higher than those of Barrett′s esophagus with moderate dysplasia (95.50±40.56 vs. 40.00±13.34, 21.00±8.31 vs. 11.83±2.92, 16.50±6.17 vs. 7.50±2.47 and 0.79±0.42 vs. 0.63±0.12, respectively), and the differences were statistically significant(t=-4.503, -3.605, -4.690 and -4.340, all P<0.01).@*Conclusion@#Barrett′s esophageal dysplasia may be related with appearance of goblet cells, and the decrease or disappearance of goblet cells may indicate the progression of Barrett′s esophagus.

Role of goblet cells in the progression of Barrett's esophagus / 中华消化杂志

Objective To investigate the clinical pathological features of Barrett's esophagus in China , and to study the relationship between the number of goblet cells and the severity of Barrett 's esophageal dysplasia.Methods From January 2008 to October 2018, in the Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital , the clinical and pathological data of 453 patients who underwent gastroscopy and pathologically diagnosed with Barrett 's esophagus were retrospectively analyzed .The clinical pathological features were compared between patients with goblet cells and patients without goblet cells . Periodic acid Schiff reaction (PAS) staining was performed on pathological slides of Barrett's esophagus with goblet cells, and the relationship between the number of goblet cells , the number of positive crypts of goblet cells and the severity of Barrett's esophageal dysplasia was analyzed .T test and chi-square test were performed for statistical analysis.Results Among 453 patients with Barrett's esophagus, 251 (55.4%) were males and 202 (44.6%) were females.There were 218 Barrett's esophagus with goblet cells , including 128 males (58.7%) and 90 females (41.3%).The average onset age was (60.6 ±11.9) years old, and the peak onset age was between 60 and 69 years old.The appearance under endoscopy mainly was circumferential type (58.2%, 127/218).There were 235 Barrett's esophagus without goblet cells , 123 males (52.3%) and 112 females (47.7%).The average onset age was (56.1 ±14.4) years old, and the peak onset age was between 50 and 59 years old.The appearance under endoscopy was mainly circumferential type (40.0%, 94/235).The incidence of dysplasia in Barrett's esophagus with goblet cells was higher than that without goblet cells (75.7%, 165/218 vs.37.0%, 87/235), and the difference was statistically significant (χ2 ＝68.501, P?0.01).PAS staining showed that goblet cells were stained purplish red .The number of goblet cells , total number of crypts , the number of positive crypts of goblet cells and the proportion of positive crypts of goblet cells of Barrett 's esophagus with mild dysplasia were all significantly higher than those of Barrett 's esophagus with moderate dysplasia (95.50 ±40.56 vs.40.00 ±13.34, 21.00 ±8.31 vs.11.83 ±2.92, 16.50 ±6.17 vs.7.50 ± 2.47 and 0.79 ±0.42 vs.0.63 ±0.12, respectively), and the differences were statistically significant ( t＝-4.503,-3.605,-4.690 and -4.340, all P?0.01).Conclusion Barrett's esophageal dysplasia may be related with appearance of goblet cells , and the decrease or disappearance of goblet cells may indicate the progression of Barrett's esophagus.

Evaluation of p53 protein expression in Barrett esophagus

Background: Loss of heterozygosity of p53 along with aneuploidy is deemed to be the early molecular steps in Barrett metaplasia-dysplasia-adenocarcinoma sequence. Objective biomarkers need to be used along with microscopy for risk stratification to predict the progression of Barrett esophagus (BE) to carcinoma. Aim: This study aims to study p53 protein expression in dysplasia and correlate the same with morphology in BE. Materials and Methods: A time-bound study was conducted from January 2011 to June 2015. All esophageal biopsies showing histological evidence of columnar epithelium with the presence of goblet cells were included. The cases which showed dysplasia were graded on hematoxylin and eosin stain. Evaluation of p53 immunohistochemistry staining was done on all the cases of BE. Dysplasia was correlated with the expression of p53 using Chi-square value (χ2) and Fischer's exact test wherever appropriate. P < 0.05 was considered to be statistically significant. Results: Of 829 esophageal biopsies received, 119 were endoscopically suspected to be BE, of which 85 cases were confirmed on microscopy. In our study, there were 75 cases negative for dysplasia (88.2%), 8 with low-grade dysplasia (LGD) (9.4%), and two with high-grade dysplasia (HGD) (2.4%). Three cases of BE had associated adenocarcinoma. Immunostaining with p53 done on all the 85 cases showed positive staining in all cases with LGD, one with HGD and two with adenocarcinoma. In the present study, immunostaining with p53 showed 90% sensitivity, 89.3% specificity, positive predictive value of 52.9%, and negative predictive value of 98.5%. Conclusion: The technical simplicity, easy availability, and comparatively lower cost enhance the role of p53 as a biomarker in risk stratification for patients with BE.

MiR-21 Suppresses Anoikis through Targeting PDCD4 and PTEN in Human Esophageal Adenocarcinoma / 华中科技大学学报（医学）（英德文版）

Anoikis is a form of apoptosis induced upon cell detachment from extracellular matrix.It has been determined that acquisition of resistance to anoikis is a critical step for tumor cell metastasis.MiR-21,the most prominent oncomiR,plays an important role in tumor progression.In this study,we revealed that up-regulation of miR-21 in human esophageal adenocarcinoma (EA) is associated with lymph node metastasis and poor survival rate.Because of the established anti-apoptosis effect of miR-21,it is tempting to speculate that miR-21 might contribute to tumor metastasis by regulating anoikis,qRT-PCR analysis demonstrated that miR-21 expression in OE33/AR cells (subpopulation of human EA OE33 cells that acquired resistance to anoikis) was significantly increased.Also,transfection of miR-21 mimics provided OE33 cells resisting to anoikis.By luciferase assays,we verified that PDCD4 and PTEN were the functional targets of miR-21.In mouse model,via tail vein injection experiment,we showed that the metastasis formation of OE33 cells in vivo could be mediated by changing the miR-21 expression pattern.Taken together,our findings suggested that miR-21 was involved in the regulation of anoikis in human EA cells.Targeting miR-21 may provide a novel strategy to prevent metastasis.

MiR-21 Suppresses Anoikis through Targeting PDCD4 and PTEN in Human Esophageal Adenocarcinoma / 华中科技大学学报（医学）（英德文版）

Anoikis is a form of apoptosis induced upon cell detachment from extracellular matrix.It has been determined that acquisition of resistance to anoikis is a critical step for tumor cell metastasis.MiR-21,the most prominent oncomiR,plays an important role in tumor progression.In this study,we revealed that up-regulation of miR-21 in human esophageal adenocarcinoma (EA) is associated with lymph node metastasis and poor survival rate.Because of the established anti-apoptosis effect of miR-21,it is tempting to speculate that miR-21 might contribute to tumor metastasis by regulating anoikis,qRT-PCR analysis demonstrated that miR-21 expression in OE33/AR cells (subpopulation of human EA OE33 cells that acquired resistance to anoikis) was significantly increased.Also,transfection of miR-21 mimics provided OE33 cells resisting to anoikis.By luciferase assays,we verified that PDCD4 and PTEN were the functional targets of miR-21.In mouse model,via tail vein injection experiment,we showed that the metastasis formation of OE33 cells in vivo could be mediated by changing the miR-21 expression pattern.Taken together,our findings suggested that miR-21 was involved in the regulation of anoikis in human EA cells.Targeting miR-21 may provide a novel strategy to prevent metastasis.

Incidence and prognosis of esophageal adenocarcinoma, Siewert type Ⅰ adenocarcinoma of esophagogastric junction and Barrett esophagus in Henan province from 2010 to 2015 / 中华消化杂志

Objective To explore the incidence and prognosis of esophageal adenocarcinoma (EAC),Siewert type Ⅰ adenocarcinoma of esophagogastric junction (AEG) and Barrett esophagus (BE) in Henan province,an area of high incidence of esophageal cancer.Methods From January 2010 to January 2015,the clinical data of 152 patients with EAC,70 patients with Siewert type Ⅰ AEG and 149 patients with BE were collected,and the clinicopathological features and treatment methods of all the patients were retrospectively analyzed.Patients with EAC and Siewert type Ⅰ AEG were followed up by telephone,while the patients with BE were followed up by telephone and endoscopy examination.The follow-up was ended in January 1st 2016 and the total follow-up period was 12 to 72 months.Chi square test,t test and one way analysis of variance were performed for comparison of pathological characteristics among groups;linear regression method was used to detect changing trends in the rates over time and Kaplan-Meier method was for survival analysis.Results The annual detection rates in five years of EAC were 0.7‰,0.9‰,0.8‰,1.1‰ and 1.1‰,respectively,suggesting an increasing trend (F=10.714,P＜0.05).The proportion of EAC to esophageal squamous carcinoma (ESC) were 2.9％,3.2％,3.1％,3.4％ and 3.8％,respectively with an increasing trend (F=17.647,P＜0.05).The one,three-and five-year overall survival rates of EAC were 57.7％,30.6％ and 15.3 ％.Among 152 patients with EAC,51 received operation and 101 patients did not.The median survival time was 14 months,and the median survival time of operation group and non-operation group was 60 months and 10 months,respectively.Survival curve layered by treatment methods indicated that the three-year survival rates of operation combined with chemotherapy group,operation group,radiotherapy or chemotherapy group and notreatment group were 82.3％,50.0％,11.2％ and 0.The three-year survival rates in operation combined with chemotherapy group,operation group,radiotherapy or chemotherapy group and no-treatment group were significantly different (x2 =1.099,2.236 and 11.431,all P＜0.01).The annual detection rates in five years of Siewert type Ⅰ AEG were 0.2‰,0.3‰,0.4‰,0.4‰,0.7‰,respectively,with an increasing trend (F=19.105,P＜0.05).The one-,three-and five-year overall survival rate of Siewert type Ⅰ AEG was 59.8％,30.5 ％ and 15.3 ％,respectively.Among 70 patients with Siewert type Ⅰ AEG,16 cases received operation,while 54 cases without operation.The median survival time of Siewert type Ⅰ AEG was 16 months,and the median survival time of operation group and non-operation group was 50 months and 13 months.The one-,three-and five-year survival rates of operation group were 87.5％,62.6％ and 43.0％ respectively,and the one-,threeand five-year survival rates of non-operation group were 50.2 ％,19.6 ％ and 0,respectively,and the difference in cumulative survival rate between the two groups was statistically significant (x2 =12.289,P＜ 0.05).The annual detection rates of BE in five years were 0.6‰,0.5‰,0.9‰,0.9‰ and 1.1‰,respectively,with an increasing trend (F=13.364,P＜0.05).Among 149 patients with BE,there were 24 cases with specialized intestinal metaplasia and six cases with dysplasia,but none of them developed into adenocarcinoma during the follow-up period.Conclusions In Henan province,an area with high incidence of esophageal cancer,there is an increasing trend in the annual detection rates in five years of EAC,Siewert type Ⅰ AEG and BE.Although the incidence of EAC and Siewert type Ⅰ AEG is not high,the prognosis is poor with low survival rate.The prognosis of non-operation group is obviously worse than that of operation group.Specialized intestinal metaplasia and dysplasia in patiens with BE are rare and have a low probability of developing into adenocarcinoma.

Incidence and prognosis of esophageal adenocarcinoma, Siewert type Ⅰ adenocarcinoma of esophagogastric junction and Barrett esophagus in Henan province from 2010 to 2015 / 中华消化杂志

Objective To explore the incidence and prognosis of esophageal adenocarcinoma (EAC),Siewert type Ⅰ adenocarcinoma of esophagogastric junction (AEG) and Barrett esophagus (BE) in Henan province,an area of high incidence of esophageal cancer.Methods From January 2010 to January 2015,the clinical data of 152 patients with EAC,70 patients with Siewert type Ⅰ AEG and 149 patients with BE were collected,and the clinicopathological features and treatment methods of all the patients were retrospectively analyzed.Patients with EAC and Siewert type Ⅰ AEG were followed up by telephone,while the patients with BE were followed up by telephone and endoscopy examination.The follow-up was ended in January 1st 2016 and the total follow-up period was 12 to 72 months.Chi square test,t test and one way analysis of variance were performed for comparison of pathological characteristics among groups;linear regression method was used to detect changing trends in the rates over time and Kaplan-Meier method was for survival analysis.Results The annual detection rates in five years of EAC were 0.7‰,0.9‰,0.8‰,1.1‰ and 1.1‰,respectively,suggesting an increasing trend (F=10.714,P＜0.05).The proportion of EAC to esophageal squamous carcinoma (ESC) were 2.9％,3.2％,3.1％,3.4％ and 3.8％,respectively with an increasing trend (F=17.647,P＜0.05).The one,three-and five-year overall survival rates of EAC were 57.7％,30.6％ and 15.3 ％.Among 152 patients with EAC,51 received operation and 101 patients did not.The median survival time was 14 months,and the median survival time of operation group and non-operation group was 60 months and 10 months,respectively.Survival curve layered by treatment methods indicated that the three-year survival rates of operation combined with chemotherapy group,operation group,radiotherapy or chemotherapy group and notreatment group were 82.3％,50.0％,11.2％ and 0.The three-year survival rates in operation combined with chemotherapy group,operation group,radiotherapy or chemotherapy group and no-treatment group were significantly different (x2 =1.099,2.236 and 11.431,all P＜0.01).The annual detection rates in five years of Siewert type Ⅰ AEG were 0.2‰,0.3‰,0.4‰,0.4‰,0.7‰,respectively,with an increasing trend (F=19.105,P＜0.05).The one-,three-and five-year overall survival rate of Siewert type Ⅰ AEG was 59.8％,30.5 ％ and 15.3 ％,respectively.Among 70 patients with Siewert type Ⅰ AEG,16 cases received operation,while 54 cases without operation.The median survival time of Siewert type Ⅰ AEG was 16 months,and the median survival time of operation group and non-operation group was 50 months and 13 months.The one-,three-and five-year survival rates of operation group were 87.5％,62.6％ and 43.0％ respectively,and the one-,threeand five-year survival rates of non-operation group were 50.2 ％,19.6 ％ and 0,respectively,and the difference in cumulative survival rate between the two groups was statistically significant (x2 =12.289,P＜ 0.05).The annual detection rates of BE in five years were 0.6‰,0.5‰,0.9‰,0.9‰ and 1.1‰,respectively,with an increasing trend (F=13.364,P＜0.05).Among 149 patients with BE,there were 24 cases with specialized intestinal metaplasia and six cases with dysplasia,but none of them developed into adenocarcinoma during the follow-up period.Conclusions In Henan province,an area with high incidence of esophageal cancer,there is an increasing trend in the annual detection rates in five years of EAC,Siewert type Ⅰ AEG and BE.Although the incidence of EAC and Siewert type Ⅰ AEG is not high,the prognosis is poor with low survival rate.The prognosis of non-operation group is obviously worse than that of operation group.Specialized intestinal metaplasia and dysplasia in patiens with BE are rare and have a low probability of developing into adenocarcinoma.

Analysis of histopathological features in 850 cases of esophageal malignant tumor / 中华消化杂志

Objective To explore the histopathological features of 850 patients with esophageal malignant tumor in 10 years.Methods From January 2002 to January 2012, 850 patients diagnosed with esophageal malignant tumor were enrolled.Tumor location, general type, pathological type and TNM stage were retrospectively analyzed.All the data were described as case number and percentage.Results Among the 850 cases of esophageal malignant tumor, 33 lesions (3.9％) located in the neck segment of esophagus, 119 lesions (14.0％) located in the upper segment, 44 lesions (5.2 ％) located in the upper-middle segment, 409 lesions (48.1％) located in the middle segment, 123 lesions (14.5 ％) located in the middle-lower segment, 122 lesions (14.4％) located in the lower segment.Among the 724 eases clearly diagnosed as esophageal malignant tumor by general type, the most cases were ulcer type (305 cases, 42.1％), followed by medulla type (260 cases, 35.9％), fungating type (80 cases, 11.0％) and constrictive type (70 cases, 9.7％), and the least cases were intraluminal type (nine cases, 1.2％).Among the 850 cases of esophageal malignant tumor, squamous cell carcinoma (794 cases, 93.4 ％) was the most common cytological type, followed by small cell carcinoma (19 eases, 2.2％), and the least common cytological type was adenocarcinoma (seven cases, 0.8 ％).Among the 724 cases with clear TNM staging, case number of Tis, T1, T2, T3 and T4 stage was eight (1.1％), six (0.8％), 271 (37.4％), 278 (38.4％) and 161 (22.2％), respectively.Among the 122 cases of distal esophageal carcinomas (104 cases with clear TNM staging), most cases were squamous cell carcinoma (112 cases, 91.8 ％), the others cases were adenocarcinoma (three cases, 2.5 ％), small cell carcinoma (three cases, 2.5 ％), basaloid squamous cell, adenosquamous, neuroendocrine carcinomas and carcinosarcoma (one case in each type, 0.8％).Conclusions Esophageal carcinoma was mostly located in the middle segment of in which squamous cell carcinoma was predominant while adenocarcinoma was less common.Esophageal cancer located at lower segment of esophagus is with a wide range of pathological spectrum, squamous cell carcinoma was still dominant, however, esophageal adenocarcinoma is rare.

Expression analysis of miRNA and target mRNAs in esophageal cancer

We aimed to investigate miRNAs and related mRNAs through a network-based approach in order to learn the crucial role that they play in the biological processes of esophageal cancer. Esophageal squamous-cell carcinoma (ESCC) and adenocarcinoma (EAC)-related miRNA and gene expression data were downloaded from the Gene Expression Omnibus database, and differentially expressed miRNAs and genes were selected. Target genes of differentially expressed miRNAs were predicted and their regulatory networks were constructed. Differentially expressed miRNA analysis selected four miRNAs associated with EAC and ESCC, among which hsa-miR-21 and hsa-miR-202 were shared by both diseases. hsa-miR-202 was reported for the first time to be associated with esophageal cancer in the present study. Differentially expressed miRNA target genes were mainly involved in cancer-related and signal-transduction pathways. Functional categories of these target genes were related to transcriptional regulation. The results may indicate potential target miRNAs and genes for future investigations of esophageal cancer.

Clinical consequences of Helicobacter pylori infection in children and its relation with the response of the gastric mucosa to the infection

Helicobacter pylori is usually acquired during childhood and remains in the gastric mucosa for years, often lifelong if untreated. It can be concluded that the gastric mucosa of children actively responds to the presence of H. pylori. Current evidences suggest that whereas H. pylori infection rarely causes peptic ulcers or gastric atrophy in children, it seems to be associated with iron deficiency and iron deficiency anemia; the evidence also suggests the infection may cause growth retardation. In contrast, H. pylori infection has been associated with a reduced risk of asthma and allergy in children and adults; also, epidemiological studies suggest that there is an inverse association between H. pylori infection and risk for esophageal adenocarcinoma. The gastric mucosa of children elicits a significant inflammatory response in the site of infection, with increased expression of toll-like receptors (TLRs) and cytokines, and increased epithelial proliferation. This response may partly be responsible for the required "immune training" needed to protect for the development of esophageal cancer, asthma, allergy or even diabetes later in life. The response may as well be associated with growth retardation, iron deficiency and increased risk for enteric infections. It then seems that our co-evolution with H. pylori has rendered benefits for human health making clear that this relationship is complex and the decision to eradicate the infection should be taken with caution.

RING Finger Proteins Are Involved in the Progression of Barrett Esophagus to Esophageal Adenocarcinoma: A Preliminary Study

BACKGROUND/AIMS: To investigate the differential expression of RING finger (RNF) proteins in Barrett esophagus (BE) and esophageal adenocarcinoma (EAC). METHODS: The differential expression of RNFs in normal esophagus (NE), BE, and EAC was screened using microarray assay. Real-time quantitative polymerase chain reaction (PCR), tissue microarray assay, and Western blot analysis were independently performed to detect the mRNA and protein expression of screened RNFs. RESULTS: The expression of nine RNFs in the BE or EAC was 2-fold higher than those in NE. Among these proteins, the RNF32 and RNF121 expression in BE was 20.3-fold and 16.4-fold higher, respectively, than that in NE, and the expression of RNF24, RNF130, RNF141, RNF139, RNF11, RNF14, and RNF159 was upregulated more than 2-fold compared with NE. The expression of nine RNFs was not only upregulated in the EAC but was also positively related to the RNF expression in BE. The PCR results also indicated increased expression of these RNFs in BE and EAC compared to NE. Furthermore, the mRNA expression of all RNFs, except for RNF141 in EAC, was dramatically higher than those in the BE. Similar results were also obtained from the Western blot analysis. CONCLUSIONS: A total of nine RNFs play critical roles in the progression of BE to EAC.