Overexpression of CAD in stomach adenocarcinoma tissues and its clinical significance

Abstract

Stomach adenocarcinoma (STAD) is one of the deadliest malignant tumors worldwide. Carbamoyl-phosphate synthetase 2 (CAD) expression is essential for categorizing and detecting STAD initiation and development. We explored the differential expression of genes (DEGs) affected by CAD overexpression and subsequently revealed the classification module of CAD-based scoring sets using weighted gene co-expression network analysis (WGCNA). Subsequently, enrichment analysis of biological functions and signaling pathways in clinically significant modules was conducted. We constructed a CAD-based clinical scoring model using univariate and multivariate Cox regression analyses. In addition, by using immune cell infiltration analysis, we investigated the interaction between CAD-based score and the immune microenvironment, identified upstream regulatory factors, including RNA binding proteins (RBPs), that affect the transcription of the STAD-related CAD-based score, and explored potential drug targets. We identified 4,977 abnormal regulatory genes related to CAD in STAD, among which the module genes most related to CAD were significantly enriched in cancer-related signaling pathways, such as VEGF, MAPK and TGF-beta signaling pathway. The CAD-based scores, T and N were identified as independent prognostic factors for STAD patients. We also found that under the influence of high expression of CAD, the infiltration level of most immune cells is lower, such as CD4 T cells and Tfh, and CAD has an inhibitory effect on the infiltration of certain immune cells. Notably, the potential drug targets PDHB and NDUFB6 are upstream regulatory factors in STAD. This study explored the role of highly expressed CAD-related genes in STAD and explored the tumorigenesis and progression of this disease. This research identified potential diagnostic and prognostic drug targets and provided new insights into the molecular mechanisms of STAD.