Methylation-Mediated Silencing of RBP7 Promotes Breast Cancer Progression Through PPAR and PI3K/AKT Pathway

Purpose Retinoid-binding protein (RBP7) is a member of the cellular retinol-binding protein (CRBP) family, which is involved in the pathogenesis of breast cancer (BRCA). The study aims to illustrate the prognostic value and the potential regulatory mechanisms of RBP7 expression in BRCA. Methods We utilized a series of bioinformatics tools, including HPA, GEPIA, UALCAN, ONCOMINE, Kaplan–Meier plotter, PROGeneV2, TISCH, LinkedOmics, UCSC Xena, MethSurv, SMART APP, bc-GenExMiner4.7, OSbrca, STRING, CARE, SwissDock and R software packages, to investigate the expression, prognostic value and functional regulatory networks of RBP7 in BRCA. Results Bioinformatics analysis with the TCGA and CPTAC databases revealed that the mRNA and protein expression levels of RBP7 in normal were higher compared to BRCA tissues. Survival analysis displayed that the lower expression of RBP7, the worse the prognosis in ER-positive (ER+) BRCA patients. Genomic analysis showed that promoter methylation result in transcriptional silencing of RBP7 in BRCA. Functional enrichment analysis demonstrated that downregulation of RBP7 expression may exert its biological influence on BRCA through the PPAR pathway and the PI3K/AKT pathway. Conclusions In summary, we identified RBP7 as a novel biomarker that is helpful for the prognosis of ER+ BRCA patients. Promoter methylation of RBP7 is involved in its gene silencing in BRCA, thus regulating the occurrence and development of ER+ BRCA through the PPAR and PI3K/AKT pathways.