Multi-target effects of flavonoids as PPARG agonists in TCGA cancers

PPARG (peroxisome proliferator-activated receptors gamma) is a nuclear receptor protein superfamily member, PPARG agonists have been proven to have broad anticancer properties in experimental studies. Associated clinical oncology investigations have been widely conducted, but no good relevant findings have been reported thus far. This might be caused by the limitations of a few cancer types of clinical studies. Simultaneously, screening natural products of PPARG agonists with minimal toxicity and side effects may aid in the clinical translation of PPARG agonists into the field of cancer. To that purpose, we investigated the association between PPARG gene expression and prognosis in 34 TCGA cancers and discovered that high PPARG gene expression was only a significant correlation (p < 0.05) with overall survival and progression-free survival in KIRP and UVM patients. An up-regulated PPARG expression with down-regulated ATP8B3 expression had the best prognosis in KIRP and UVM patients revealed by differential expression analysis, KEGG enrichment analysis, and tumor single-cell sequencing analysis. Flavonoids in yellow tea were demonstrated may both activate PPARG and inhibit the action of ATP8B3 using quantitative structure-activity relationships and molecular docking. As natural PPARG agonists, tea flavonoids are worth additional investigation in the field of clinical cancer research, especially in KIRP and UVM.