Effects Of FGD6 As A Prognostic Marker On The Progression Of Gastric Cancer And Construction Of A Glycolysis-Related Long Noncoding RNA Signature For Predicting Prognosis In Gastric Cancer Patients

Objective(s):Gastric cancer(GC)is one of the most incidence and mortality cancers worldwide,with a higher incidence in men than in women.It is reported that most of GC patients are diagnosed with advanced stage,led to a 5-year survival rate of only25-30% for patients with GC in China.Clinical treatment strategies include surgery,chemotherapy,radiotherapy,and targeted therapies and so on,but the prognosis of GC patients with advanced stages remains poor.Therefore,it is necessary to find new and effective prognostic biomarkers to improve the survival rates of GC patients.Methods:This study was divided into two parts.The first part: The expression of FGD6 gene in GC patients in The Cancer Genome Atlas(TCGA)database was analyzed to get a preliminary conclusion.Then,our conclusions were verified in Gene Expression Omnibus(GEO)database and patient samples from Ruijin Hospital.The relationship between the FGD6 level and various clinicopathological features was analyzed by Logistic regression and Univariate Cox regression.Multivariate Cox regression analysis was used to evaluate whether FGD6 was an independent prognostic factor for survival of patients with GC.The relationship between FGD6 and overall survival(OS)time was explored by Kaplan–Meier method.In addition,gene set enrichment analysis(GSEA)was performed to investigate the possible biological processes of FGD6.In gastric cancer cell,the expression level of FGD6 was knocked down by transient transfection of small interfering RNA,and the effect of FGD6 knockdown on the proliferation and migration of gastric cancer was evaluated by Cell Counting kit(CCK-8)and Cell migration assay.The second part: Glycolysis-related genes were obtained from the Molecular Signatures Database(MSig DB),lncRNA expression profiles and clinical data of GC patients were obtained from The Cancer Genome Atlas database(TCGA).Univariate Cox regression analysis,Least Absolute Shrinkage and Selection Operator(LASSO)and multivariate Cox regression analysis were used to construct prognostic glycolysisrelated lncRNA signature.The specificity and sensitivity of the signature was verified by receiver operating characteristic(ROC)curves.We constructed a nomogram to predict the 1-year,3-year,and 5-year survival rates of GC patients.Besides,we analyzed the relationship between immune infiltration and risk score in high risk and low risk groups.Gene set enrichment analysis(GSEA)was employed to further explore the biological pathways in the high-risk group.Results:In the first part of the study,it was found that FGD6 expression was elevated in GC tissues compared with adjacent normal tissues.The high expression of FGD6 was related to high histological grade,stage,T classification and poor prognosis of gastric cancer.Multivariate cox regression analysis showed that FGD6 was an independent prognostic factor for survival of patients with GC.GSEA identified that the high expression of FGD6 was mainly enriched in regulation of actin cytoskeleton.In vitro experiments showed that knockdown of FGD6 could reduce the efficiency of gastric cancer cell proliferation and migration.The second part performed prognostic signatures based on nine glycolyassociated lncRNAs,which are AL391152.1,AL590705.3,RHOXF1-AS1,CFAP61-AS1,LINC00412,AC005165.1,AC110995.1,AL355574.1 and SCAT1.The area under the ROC curve(AUC)values at 1-year,3-year,and 5-year were 0.765,0.728 and 0.707 in the train group,and 0.669,740 and 0.807 in the test group,respectively.In addition,the nomogram could efficaciously predict the 1-year,3-year,and 5-year survival rates of the GC patients.Then,we discovered the prediction ability of the risk score on immunotherapy outcomes of GC patients.Finally,GSEA revealed that the signature was mainly associated with the calcium signaling pathway,extracellular matrix(ECM)receptor interaction,and focal adhesion in high-risk group.Conclusion(s):This study suggests that FGD6 is a biomarker for predicting the prognosis of GC patients.In addition,the model established in this study has a good ability to predict the overall survival of GC and can provide new insights into immunotherapy strategies.