Prognostic Value Of LCP2 Gene In Remodeling Tumor Microenvironment And Predicting Response To Immunotherapy In Pancreatic Head Ductal Adenocarcinoma

Objective:Based on comprehensive bioinformatics analysis,we screened tumor microenvironment-related genes in pancreatic head ductal adenocarcinoma,and explored the correlation between LCP2 gene and immune infiltrating cells and immunotherapeutic response in the tumor microenvironment of pancreatic head ductal adenocarcinoma.Methods: Transcriptome RNA-seq profiles were downloaded from the Cancer Genome Atlas(TCGA)and GTEx databases.Perl software and R-language were applied to analyze the common differentially expressed genes(Co-DEG)in patients with pancreatic head ductal adenocarcinoma.The protein-protein interaction network of Co-DEG was constructed by the STRING database,the pivotal genes were filtered by Cytoscape.Correlation of immune-related biological features of the LCP2 gene with common inhibitory checkpoint molecules was explored via gene set enrichment analysis(GSEA)and CIBERSORT.Results: In the pancreatic cancer cohort of the TCGA,the immune and stromal scores of the tumor microenvironment were positively correlated with the overall survival of patients with pancreatic head ductal adenocarcinoma(P < 0.05).487 differentially expressed genes(DEG)were screened via immune score.414 DEG were screened via stromal score.653 DEG were screened via ESTIMATE score.201 common differentially expressed genes was picked via the intersection of genes from above-mentioned the three scores.The top five pivotal genes with high connectivity were filtered by protein-protein interaction network analysis,which were PTPRC,CD86,CD4,ITGB2,and LCP2.The LCP2 gene was further analyzed.The LCP2 gene was highly expressed in ductal adenocarcinoma of the pancreatic head tissue,and survival analysis revealed that patients with high expression of LCP2 had a better prognosis(P<0.05).GSEA revealed that the high-expression group for LCP2 was mainly enriched in immunobiological processes,while the low-expression group for LCP2 was mainly enriched in metabolism-related pathways.Immunoinfiltration analysis indicated that the primitive B cells,T cells,M0 macrophages and NK cells in the high expression group of LCP2 gene were significantly different from those in the low expression group(all P<0.01).LCP2 gene is associated with common inhibitory checkpoint molecules((PD1,PD-L1,CTLA4,CD86,TIM-3,LAG3 and TIGIT,R=0.78,0.9,0.63,0.7,0.8,0.61,0.86,all P<0.001).Conclusion: In this study,we screened the pivotal gene LCP2 related to tumor microenvironment in ductal adenocarcinoma of the pancreatic head tissue through bioinformatics analysis.Its expression is closely related to immune related biological processes and activated immune infiltrating cells;And it is positively correlated with common immune checkpoint molecules,which has potential value in predicting immune therapy response and provides new therapeutic targets for immunotherapy of pancreatic duct adenocarcinoma.