AUTHOR=Wang Yumian , Zhang Li , Chen Han , Yang Juan , Cui Yun , Wang Hong TITLE=Coronary artery disease-associated immune gene RBP1 and its pan-cancer analysis JOURNAL=Frontiers in Cardiovascular Medicine VOLUME=10 YEAR=2023 URL=https://www.frontiersin.org/journals/cardiovascular-medicine/articles/10.3389/fcvm.2023.1091950 DOI=10.3389/fcvm.2023.1091950 ISSN=2297-055X ABSTRACT=Purpose

To identify immune-related biomarkers in coronary artery disease (CAD), investigate their possible function in the immunological milieu of tumors, and initially investigate the mechanisms and therapeutic targets shared by CAD and cancer.

Methods

Download the CAD-related dataset GSE60681 from the GEO database. GSVA and WGCNA analyses were performed based on the GSE60681 dataset to identify the modules most pertinent to CAD, identify candidate hub genes and finally intersect the genes associated with immunity downloaded from the import database to find the hub genes. The GTEx, CCLE, and TCGA database were used to examine the expression of the hub gene in normal tissues, tumor cell lines, tumor tissues, and different tumor STAGES. One-factor cox and Kaplan-Meier analyses were performed to explore the prognosis of hub genes. Hub gene methylation levels in CAD and cancer were analyzed in the diseaseMeth 3.0 and ualcan databases, respectively. R package CiberSort processed the GSE60681 dataset to assess immune infiltration in CAD. TIMER2.0 evaluated hub genes with pan-cancer immune infiltration. The hub genes were analyzed for drug sensitivity and correlation with TMB, MSI, MMR, cancer-related functional status, and immune checkpoints in different tumors. Finally, GSEA was carried out on the crucial genes.

Results

WGCNA were used to pinpoint the green modules that were most closely related to CAD and intersections with immune-related genes were taken to remember the pivotal gene RBP1. RBP1 is hypermethylated in CAD and multiple cancers. Its expression levels in different cancers were associated with poor prognosis of cancer, with significant expression levels at higher stages of cancer staging. The immune infiltration results showed that RBP1 was closely associated with CAD and tumor-associated immune infiltration. The results indicated that RBP1 was strongly correlated with TMB, MSI, MMR, cancer-associated functional status, and immune checkpoints in various cancers. RBP1 was related to the sensitivity of six anticancer drugs. GSEA showed RBP1 was associated with immune cell activation, immune response, and cancer development.

Conclusion

RBP1 is a pivotal gene associated with immunity in CAD and pan-cancer and may mediate the development of CAD and cancer through immunity, making it a common therapeutic target for both.