Prognostic Significance and Immune Microenvironment Correlates of coagulation factor 2 receptor in Gastric Cancer and Retrospective Verification

Abstract

Objective: To assess the prognostic role of coagulation factor 2 receptor in gastric cancer.

Method: The retrospective study was conducted at ?? from ?? to ?? and comprised pathological samples of patients having undergone radical gastrectomy between ?? and ?? in the General Surgery Department of Xishan People’s Hospital, China. Correlation of coagulation factor 2 receptor expression with clinical features, deoxyribonucleic acid methylation, and the richness of tumour immune cell infiltration were analysed in the samples using data from The Cancer Genome Atlas, University of California, Santa Cruz Xena, Tumour IMmune Estimation Resource-2.0 and Gene Expression Omnibus databases. Prognostic impact was evaluated using Kaplan-Meier, Cox regression, nomograms and MethSurv. Gene Ontology and Kyoto Encyclopaedia of Genes and Genomes enrichment analyses were performed on coagulation factor 2 receptor co-expressed genes.

Results: Of the 12 patients, 9(75%) were male and 3(25%) were females. There were 8(66.7%) patients aged >60 years, while 4(33.3%) were aged <60 years. Coagulation factor 2 receptor was significantly upregulated in gastric cancer (p<0.001), correlating with histological grade and clinical stage. It was an independent prognostic factor (hazard ratio: =2.004; 95% confidence interval: 1.069-3.755], p<0.05). High expression or low promoter methylation predicted poorer survival (p<0.05). Immunoinfiltration showed positive correlations with CD8+ T cells, fibroblasts and macrophages. Single-cell assays indicated coagulation factor 2 receptor expression in fibroblasts, CD8+ T cells, and plasma cells. Kyoto Encyclopaedia of Genes and Genomes analysis revealed enrichment in cancer pathways, PI3K-Akt and MAPK signalling. Gene set enrichment analyses suggested high expression of coagulation factor 2 receptor gene correlated with gastric cancer via extracellular matrix receptor interaction, focal adhesion and cancer pathways.

Conclusions: Coagulation factor 2 receptor may be an independent prognostic biomarker for gastric cancer and may correlate with immune infiltration.

Key Words: Coagulation factor 2 receptor, F2R, Gastric cancer, Prognosis, Immune infiltration, Functional enrichment.