Immunoinfiltration-related gene SERPINE1 is a novel biomarker for diagnosis and prognosis of stomach adenocarcinoma discovered via high throughput transcriptome data mining combined with bioinformatics

Abstract

Abstract Stomach adenocarcinoma (STAD) is a type of cancer as it has frequently developed into the advanced stage at diagnosis and mortality. Several factors influence the prognosis of STAD, including the expression and regulation of immune cells in the tumor microenvironment (TME). In this study, we aim to find biomarkers related to the diagnosis and prognosis of gastric cancer, hoping to provide new ideas for the diagnosis and treatment of gastric cancer in the future. STAD and normal patient RNA sequencing data sets are accessed from The Cancer Genome Atlas (TCGA database). Differential genes are determined and obtained using the R package DESeq2. The stromal, immune, and ESTIMATE scores are calculated using the algorithm ESTIMATE, and based on this, the R package WGCNA is used to screen modular genes. Subsequently, the intersection between the modular gene and the differential gene was taken and the STRING database was used for PPI network module analysis. The R packages clusterProfiler, enrichplot, and ggplot2 were used for GO and KEGG enrichment analysis. Cox regression analysis was used to screen survival-related genes, and finally, the R package Venn Diagram was used to take the intersection and obtain 7 hub genes. The time-dependent ROC curve and Kaplan-Meier survival curve were used to find the SERPINE1gene, which plays a key role in prognosis. Finally, the expression pattern, clinical characteristics, and regulatory mechanism of SERPINE1 were analyzed in STAD. This study revealed that the expression of SERPINE1 was significantly increased in the samples from STAD compared with normal samples. Cox regression analysis, time-dependent ROC curve and Kaplan-Meier survival curve showed that SERPINE1 was significantly related to the adverse prognosis of STAD patients. The expression of SERPINE1 increased with the progression of T, N, and M classification of the tumor. In addition, the results of immune infiltration analysis showed that the expression of CD4+ T cells, B cells, CD8+ T cells, macrophages, neutrophils and other immune cells were higher in the group with high SERPINE1 expression than in the group with low SERPINE1 expression. SERPINE1 was closely related to immune cells in the STAD immune microenvironment and had a synergistic effect with the immune checkpoints PD1 and PD-L1. In conclusion, this study proves that SERPINE1 can be used as a prognostic and diagnostic biomarker for STAD and a potential target for immunotherapy.