Expression Of TM4SF5 In Gastric Adenocarcinoma And Its Effect On The Prognosis

Background and objectiveGastric cancer is one of the most common malignant tumors in the digestive system.The incidence of gastric cancer is 4th in the world,and it is the second leading cause of cancer death in the world.It has a high morbidity and mortality.There are many reasons for the pathogenesis of gastric cancer,including the influence of geographical factors,Changes in diet,genetic changes and Helicobacter Pylori infections.Surgery is the only radical treatment for gastric cancer at present,but the clinical symptoms of gastric cancer generally appear so late and lacking of specificity that most of the patients have been to the advanced gastric cancer,lost the opportunity of operation.The comprehensive treatment mode based on chemotherapy is the current modle of treatment for advanced gastric cancer,but the severe side effects caused by chemotherapy are serious.As well as the appearance of drug-resistant genes makes the clinical benefit rate of patients is not high.With the study of molecular mechanism,targeted therapy has became a rapidly developing treatment mode.At present,there are few targeted drugs for gastric cancer,so it is the key to explore the molecular mechanism of gastric carcinogenesis and development,to find the target to inhibit the proliferation and metastasis of gastric cancer.TM4SF5 is a transmembrane protein superfamily,consisting of two extrace llular loops and a cytoplasmic loop and the N-termini and C-termini,containi ng four transmembrane domains with multiple transmembrane protein.TM4SF5 can form complexes mediated intracellular signal transduction to regulate cell d ifferentiation,proliferation and migration,such as the guide tumor TM4SF5 and integrin mediated binding and cell migration;TM4SF5 combined with growth factor receptor,and enhanced MMP activation,promote the formation of new blood vessels within the tumor;TM4SF5 can also interact with CD44 to promot e the circulation of tumor cells such as self-renewal.It is widely studied that TM4SF5 transduces epithelium-mesenchymal transition in hepatocellular carcino ma,changes the cytoskeleton,reduces the adhesion between cells.TM4SF5 can also be highly expressed in esophageal carcinoma,and affects the survival of p atients.However,the expression of TM4SF5 in gastric carcinoma and whether the expression of TM4SF5 affects the prognosis of gastric cancer has not been reported.In this study,the expression of TM4SF5 mRNA in gastric adenocarcinoma and paracancerous tissues was detected by RT-PCR technique.Immunohistochemical technique was used to detect the expression of TM4SF5 protein in gastric adenocarcinoma and paracancerous tissues.The purpose of this study was to explore the differences in expression of TM4SF5 mRNA and protein in cancer and paracancerous tissues,and the relationship between the expression level and clinicopathological features and survival of patients.Providing directions for TM4SF5 in the occurrence,development,prognostic evaluation and targeted therapy of gastric cancer and so on.Methods1.Collections of tissue samples:(1)Collections of fresh tissue samples:46 cases of gastric carcinoma were selected from December 1,2015 to March 31,2016 in gastrointestinal surgery,the First affiliated Hospital of Zhengzhou University.Collect the Cancer and paracancerous fresh tissues stored in-80 ? refrigerator in the operating room;(2)Collections of paraffin tissue samples : 76 cases of gastric carcinoma were selected from January 1,2012 to December 31,2012 at the first affiliated Hospital of Zhengzhou University who has undergone surgical resection.,Check the patient's history,register the patient's pathological number,and borrow the wax pieces corresponding to cancer and paracancerous tissues from our department of pathology.2.Quantitative real time polymerase chain reaction(qRT-PCR)was used to detect the relative expression of TM4SF5 mRNA in 46 fresh frozen gastric adenocarcinoma tissues and its adjacent tissues.Analyze the relationship between the expression of TM4SF5 mRNA in gastric carcinoma and the clinicopathological features.3.Immunohistochemical method was used to detect the expression of TM4SF5 protein in 76 paraffin-embedded gastric adenocarcinoma tissues and paracancerous tissues.Compare expression of TM4SF5 protein in gastric cancer tissues with its adjacent tissues and analyze the relationship between the expression of TM4SF5 protein in gastric carcinoma and the clinicopathological features.4.76 cases of patients with gastric adenocarcinoma were followed up by medical record or telephone.Recorde the time of progression and survival of gastric cancer.The deadline of follow-up was September 30,2017.5.Application of SPSS21.0 software to statistical analysis of data Results1.q RT-PCR results showed that the expression of TM4SF5 mRNA in gastric adenocarcinoma tissues was higher than that in adjacent tissues,and the difference was statistically significant(P=0.0003),There were no significant differences of the expression of TM4SF5 mRNA in gender,age,tumor size,stage,degree of differentiation,location of gastric adenocarcinoma,lymph node metastasis and depth of invasion(P > 0.05).2.The results of immunohistochemistry showed that the expression of TM4SF5 protein was positive or strongly positive in gastric adenocarcinoma tissues,and the positive rate was 59.2%,and that in the corresponding paracancerous tissues was weak expression or negative expression.The positive expression rate of TM4SF5 protein was only 13.2.TM4SF5 protein in cancer was higher than that in adjacent tissues,and the difference was statistically significant.The expression of TM4SF5 protein was correlated with lymph node metastasis(P = 0.008)and depth of invasion(P = 0.007),and it was not related to gender,age,tumor size,stage,the degree of differentiation and the location of its occurrence(P >0.05).3.Prognostic Survival Analysis of 76 patients.(1)The results of one-factor analysis showed that the expression of TM4F5 protein and pTNM stage of tumor affected DFS,OS;(2)The results of stratified analysis showed that the expression of T4SF5 protein in the same stage had no effect on the DFS(P>0.05).(3)The results of multivariate analysis showed that the expression of TM4SF5 protein and pTNM stage of tumor were an independent factor which affecting DFS in patients(P < 0.05).Conclusions1)The relative expression of TM4SF5 mRNA and the expression of TM4SF5 protein in gastric adenocarcinoma were higher than those in paracancerous tissues,suggesting that TM4SF5 might be related to the occurrence of gastric cancer.2)The expression level of TM4SF5 protein is related to the depth of invasion and lymph node metastasis.The higher the expression level,the more invasive degree is,the more likely lymph node metastasis occurs.It suggests that TM4SF5 may promote the invasion and metastasis of gastric cancer.3)The level of TM4SF5 protein expression affects the prognosis of patients.The higher the expression level,the shorter the DFS and OS of the patients.TM4SF5 is an independent influencing factor for the determination of DFS in gastric cancer patients.