Insulin-driven Tumor Hub Gene Screening And Prognostic Analysis

Objectives:Based on a variety of cancer-related databases,bioinformatics methods were used to screen out genes related to the occurrence and development of pancreatic cancer and colorectal cancer,and these genes were compared with the insulin resistance pathway to identify hub genes.Our research will provide potential biomarkers for the early diagnosis,prognosis and treatment of pancreatic cancer and colorectal cancer,and theoretical support for the development of tumor-targeted drugs.Methods:1.Data processing and preliminary analysisRNA-seq and m RNA gene expression data and clinical data of pancreatic and colorectal cancers were downloaded from the TCGA database and the GEO database.Data set preprocessing,gene differential expression analysis,enrichment analysis,and survival analysis were performed by using R scripts.2.Screening hub genes of cancerCytoscape software was used to perform hub gene and submodule analysis of differentially expressed genes and combined with survival analysis to screen out candidate genes.The candidate genes and insulin resistance pathway genes were constructed into a PPI network to obtain the hub genes.3.Validation and prognostic analysis of hub genesGEPIA online tool was used to validate the results of gene expression and survival analysis of the hub genes.TIMER database was used to conduct immune infiltration analysis of hub genes.DGIdb database was used for gene-drug interaction analysis of hub genes.Results:1.Pancreatic cancer analysis(1)Based on gene differential expression analysis,213 differentially expressed genes(155 up-regulated,58 down-regulated)were screened out.Based on enrichment analysis,the differentially expressed genes were mainly enriched in ECM-receptor interaction,IL-17 signaling pathway,transcriptional dysregulation in cancer,PI3K-Akt signaling pathway and etc.(2)9 hub genes(ECT2,TOP2 A,ANLN,CENPF,DLGAP5,ITGA2,TGFBI,MMP11,PLAT)interacted with the insulin resistance pathway were screened out by protein interaction network analysis,and the results of gene expression and survival analysis of these genes were validated(P<0.05)in GEPIA platform.(3)PLAT was identified as novel biomarker of insulin-driven pancreatic cancer.PLAT expression was up-regulated in pancreatic cancer patients compared to controls and was significantly associated with overall survival.In pancreatic cancer samples,PLAT expression was positively correlated with infiltration of CD8+ T cells,macrophages,neutrophils and dendritic cells.9 PLAT-targeted drugs were identified,including MELPHALAN,BORTEZOMIB,NAPROXEN,UROKINASE,EPOETIN BETA,ATORVASTATIN,RALOXIFENE,CHEMBL290376,AMINOCAPROIC ACID.2.Colorectal cancer analysis(1)281 differentially expressed genes(115 up-regulated,166 down-regulated)were screened out and mainly enriched in microvillus,cytokine-cytokine receptor binding,chemokine receptor binding,mitotic and nuclear division,and etc.(2)6 hub genes were identified as related to insulin resistance based on protein interaction network,including SCG2,TIMP1,GPX3,BUB1,CXCL2,RNASEH2 A,and the expression level and survival period of these genes were validated as significant(P<0.05)in colorectal cancer tissues compared to normal tissues,except SCG2.(3)RNASEH2A was charactered as a novel biomarker related to insulin resistance in colorectal cancer.The expression of RNASEH2 A was upregulated in colorectal cancer patients compared to controls and was significantly associated with overall survival.The results of immune infiltration analysis of colorectal cancer showed that RNASEH2 A expression was positively correlated with infiltration of CD8+ T cells and macrophages.The results of DGIdb analysis showed that PROGESTERONE and CAPSAICIN may be the targeted drugs to RNASEH2 A.Conclusion:1.ECT2,TOP2 A,ANLN,CENPF,DLGAP5,ITGA2,TGFBI,MMP11 and PLAT may be the hub genes in the formation and development of pancreatic cancer.As a novel biomarker,PLAT may be of importance for the diagnosis,prognosis and treatment of insulindriven pancreatic cancer.2.SCG2,TIMP1,GPX3,BUB1,CXCL2 and RNASEH2 A may be the hub genes in the generation and development of colorectal cancer,and play an important role in insulin-driven colorectal cancer.Among them,RNASEH2 A may have the potential to be a novel molecular biomarkers and therapeutic targets to colorectal cancer.