Expression Of FN1 In Gastric Cancer And Relationship With Clinical Outcome

ObjectiveThis study aimed to evaluate the correlations of expression of Fibronectin(FN1)with clinicopathological features and overall survival(OS)in gastric cancer(GC)patients.MethodsIn this study,we investigated the expression of FN1 via immunohistochemistry(IHC)in 190 GC patients and the mRNA data from The Cancer Genome Atlas(TCGA),the Gene Expression Omnibus(GEO)dataset and Oncomine.Results1.The results of public database analysis showed that FN1 expression levels were up-regulated in 8 independent cohort tumors of gastric cancer and adjacent tissues.All cohort meta-analysis further confirmed that the average difference of increased expression of FN1 in tumors was 1.99(p < 0.001).The expression of FN1 in tumor tissues was correlated with T stage(Cohen's d =-0.22,95% CI=-0.35,-0.09,P=0.0005),and the degree of differentiation(Cohen's d =-0.22,95% CI =-0.38,-0.05,P=0.000)related to histological classification(Cohen's d =-0.23,95% CI =-0.36,-0.10,P=0.0004).2..Kaplan-Merier survival analysis in the database showed that high FN1 expression was associated with adverse prognosis in four of the six cohorts with total survival(OS)information(P < 0.05).In three cohorts with disease-free survival(DFS),high FN1 expression was associated with adverse prognosis(P < 0.05).Meta-analysis showed that OS(HR = 1.67,P < 0.001)and DFS(HR = 1.87,P < 0.001)of patients with high expression of FN1 were shorter than those with low expression of FN1.Subgroup analysis showed that the high expression of FN1 was an unfavorable prognostic factor for OS and DFS in stage ? and ? patients,but it was not related to prognosis in stage ? and ? patients.3.IHC results showed that E-FN1 expression was negative in normal epithelial cells and S-FN1 was low..E-FN1 expression rate was 44.7%(85 cases)in 190 cases of gastric adenocarcinoma.S-FN1 expression was no/weak in 11 cases(5.8%),moderate in 71 cases(37.4%)and strong staining in 108 cases(56.8%).There was no correlation between E-FN1 and S-FN1(P=0.112).The expression of E-FN1 in gastric cancer was correlated with tumor size(P = 0.037),but not with age,sex,depth of invasion and degree of differentiation(P > 0.05).4.Survival analysis in IHC group showed that the overall survival and disease-free survival of patients with high expression of E-FN1 protein were shorter than those with low expression of E-FN1 protein.Subgroup analysis showed that the high expression of E-FN1 was an unfavorable prognostic factor for OS and DFS in stage ? and? patients,and the expression of E-FN1 was not correlated with prognosis in stage?and ? patients.Cox model showed that high expression of E-FN1 was an independent risk factor for prognosis of gastric cancer(HR = 0.480,95% CI = 0.336-0.686,P < 0.01).ConclusionThe expression levels of FN1 mRNA and protein in gastric cancer were higher than those in adjacent tissues.High expression of FN1 at gene and protein levels is a negative prognostic factor for gastric cancer patients.FN1 could be used as a biomarker for poor prognosis of gastric cancer patients.