Clinical Significance Of GCNT3 Expression In Non-small Cell Lung Cancer

Objective:Lung cancer is a serious threat to human health due to its high incidence,high mortality and poor prognosis.Non-small cell lung cancer(NSCLC)accounts for80%–85%of all histological type of lung cancer.However,there are few clinically prognostic markers for patients with lung cancer.It is necessary to find more effective markers as prognostic predictors to further improve the prediction of the prognosis of NSCLC patients.Glycosyltransferase enzyme 3,also known as C2GNT,C2/4GnT or GNTM,is a member of the beta-1,6-N-acetylglucosaminyltransferase(beta-1,6GnT)gene family that plays a crucial role in glycan synthesis.At present,a small amount of researches have indicated that the expression of GCNT3 is closely related to different kinds of tumors.Our group screened GCNT3 high expression in NSCLC patients by expression profile chip in the early stage.The study aimed to investigate the expression and functional significancer of GCNT3 in NSCLC and to provide potential prognostic marker and new therapeutic target for NSCLC.Methods:Tissue samples from patients with NSCLC were collected to estimate GCNT3 expression and explore the relationship between GCNT3 expression level and clinicopathological features,overall survival(OS)and progression-free survival(PFS).In addition,the effects of GCNT3 on proliferation,invasion and migration of NSCLC cells were studied by cell function and expected that GCNT3 can predict the prognosis of NSCLC and guide futher treatment.1.In this study,we used quantitative real-time polymerase chain reaction(qRT-PCR)and western blot(WB)to examine the mRNA and protein expression of GCNT3 in paired NSCLC tissues and adjacent non-tumor tissues.2.In addition,164 NSCLC patients were estimated for GCNT3 expression by immunohistochemistry(IHC)and the correlation between GCNT3 expression and clinicopathological features were analyzed.The correlation between GCNT3expression and clinicopathological characteristics was compared by the?~2 test.The survival rate curves were drew using the Kaplan-Meier method,and the differences between survival curves were compared by the log-rank test.Univariate and multivariate cox regression analysis were used to analyze the prognostic variables.3.NSCLC cell line A549 was constructed to inhibit the expression of GCNT3.The effects of GCNT3 on proliferation and migration of NSCLC cells were studied by cell proliferation test,scratch test and Transwell test.Results:The expression levels of GCNT3 mRNA and protein in NSCLC tissues were both significantly higher than adjacent non-tumor tissues.In the 164 patients with NSCLC,high GCNT3 expression level was associated with gender,smoking,histology and pathological stage.Kaplan-Meier analysis displayed significant differences among different GCNT3 expression level groups in both OS and progression-free survival PFS(P<0.05).NSCLC patients with positive expression of GCNT3 showed poor OS and PFS.Multivariate analysis demonstrated that GCNT3expression remained as an independent prognostic factor in NSCLC patients(P<0.05).Cell function experiments showed that the proliferation and migration ability of NSCLC cells were significantly attenuated after inhibition of GCNT3 expression(P<0.01),GCNT3 promotes proliferation and migration of A549 cells.Conclusion:GCNT3 was highly expressed in NSCLC tumor tissues.Positive expression of GCNT3 was associated with unfavourable OS and PFS in patients with NSCLC.GCNT3 promotes the proliferation and metastasis of NSCLC cells,which might act as a potential prognostic biomarker for NSCLC.