| Research background and purpose: Gastric cancer is the world’s fifth-largest malignant tumor that seriously endangers human health,and its mortality rate ranks fourth.The incidence and mortality of cancer in my country far exceed those of other countries.The pathology of gastric mucosa is a multi-step process,and the heterogeneity is particularly significant in gastric cancer.How to early detect and treat precancerous lesions in time is the key to reducing the mortality of gastric cancer.Currently,tumor classification is undergoing a transition from morphology to molecular typing based on gene expression profile characteristics,which is helpful for accurate treatment and prognostic evaluation of cancer patients.Several molecular classifications of gastric cancer proposed at present are closely related to the clinical pathology and prognosis of patients,and have reference value for the precise diagnosis and treatment of gastric cancer in the future.However,due to ethnic differences and tumor heterogeneity,there has not been a consensus on the molecular classification of gastric cancer;whether the existing molecular classification is applicable to Chinese patients needs to be further explored.Based on the national conditions of the majority of patients with advanced gastric cancer in our country,this research adopted immunohistochemistry methods and in situ hybridization methods which were clinically widely available,and selected 5 molecular markers of MLH1,EBV,P53,HER-2 and E-cadherin,to explore its expression and clinical significance in gastric cancer.Methods: From January 1,2016 to December 31,2017,tissue specimens from 141 patients with gastric cancer who were diagnosed pathologically and treated with surgery in the First Affiliated Hospital of Xi’an Jiaotong University were selected,and 25 cases of normal tissue adjacent to cancer were collected at the same time.The expression of EBER,MLH1,P53,HER-2,and E-cadherin were analyzed;follow-up the patients,and the follow-up end point was the death of the patient or December 31,2020.The independent risk factors that affect the prognosis of patients with gastric cancer among these 5 molecules were creened,its relationship with the clinical pathology of patients were analyzed,its value in the diagnosis and prognosis of gastric cancer were explored,and possible signal pathways involved in the occurrence and development of gastric cancer were look for.Results:1.Among the 141 patients,males accounted for 68.79%(97/141),aged between 29 and 87 years old,with a median age of 56 years old.People with a history of smoking accounted for 53.90%(76/141);Lauren classification: intestinal type accounted for 43.97 %(62/141),diffuse type accounted for 37.59%(53/141),mixed type accounted for 18.44%(26/141);degree of differentiation: high differentiation accounted for 2.84%(4/141),moderate differentiation accounted for 34.04%(48/141)),poorly differentiated accounted for 63.12%(89/141);TNM staging: stage I accounted for 4.26%(6/141),stage II accounted for 24.11%(34/141),stage III accounted for 69.50%(98/141),stage IV only 2.13%(3/141);lymphatic infiltration accounted for 59.57%(84/141),nerve infiltration accounted for20.57%(29/141),lymph node metastasis accounted for 68.79%(97/141),postoperative adjuvant chemotherapy accounted for 93.62%(132/141).2.The results of tissue immunohistochemistry and in situ hybridization showed that EBER,P53 and HER-2 were highly expressed in gastric cancer tissues and low in adjacent tissues;MLH1 and E-cadherin were not expressed in gastric cancer tissues and highly expressed in adjacent tissues.Among 141 patients with gastric cancer,EBER negative accounted for 4.96%(7/141),positive accounted for 95.04%(134/141);MLH1 negative accounted for 12.06%(17/141),and positive accounted for 87.94%(124/141);P53 wild type accounted for 58.87%(83/141),mutant type accounted for 41.13%(58/141);HER-2negative accounted for 90.78%(128/141),positive accounted for 9.22%(13/141);E-cadherin negative accounted for 11.35%(16/141),positive accounted for 88.65%(125/141).3.Univariate and multivariate COX regression analysis showed that lymph node metastasis,no postoperative adjuvant chemotherapy,MLH1 positive,HER-2 positive,and E-cadherin negative were independent risk factors affecting the prognosis of gastric cancer(P<0.05).4.The expression of MLH1 in gastric cancer patients was related to lymph node metastasis,the expression of HER-2 was related to Lauren classification and lymph node metastasis,and the expression of E-cadherin was related to the degree of differentiation,TNM stage,lymphatic invasion and lymph node metastasis(P<0.05).5.The overall survival rate of MLH1 negative patients was 72.22%.Since the overall survival rate was greater than 50% during the follow-up period,there was no median survival time;the median survival time of MLH1 positive patients was 40 months(95%CI:29.078-50.922),the difference of the two groups was statistically significant(P<0.05);The area under the ROC curve was 0.714(95%CI: 0.613～0.802),the sensitivity was 66.67%,and the specificity was 76.19%.The median survival time of HER-2 positive and negative patients was 22 months(95%CI: 0.862～43.138)and 44 months(95%CI: 33.323～54.677),the difference was statistically significant(P<0.05);The area under the ROC curve was0.901(95%CI: 0.831～0.949),the sensitivity was 94.44%,and the specificity was 85.71%.The median survival time of E-cadherin positive and negative patients was 45 months(95%CI: 35.228～54.772)and 10 months(95%CI: 8.055～11.945),the difference was statistically significant(P<0.05);The area under the ROC curve was 0.877(95%CI:0.796～0.934),the sensitivity is 94.12%,and the specificity is 81.25%.6.GSEA functional enrichment analysis results showed that MLH1 was involved in the oxidative phosphorylation pathway of gastric cancer,E-cadherin was involved in the adhesion junction of gastric cancer,and Her-2 was involved in the chemokine signaling pathway of gastric cancer(NOM P<0.05,FDR Q<0.25).Conclusion: MLH1,HER-2,and E-cadherin are independent risk factors affecting the prognosis of gastric cancer,and they are all related to a variety of clinicopathological indicators,and have important clinical significance in the diagnosis and prognosis of gastric cancer.In addition,studying the pathogenesis of gastric cancer based on predicted related signal pathways also provides a new direction for future research. |
PDF Full Text Request