Divulging a Pleiotropic Role of Succinate Receptor SUCNR1 in Renal Cell Carcinoma Microenvironment

The succinate receptor, SUCNR1, has been attributed to tumor progression, metastasis, and im-mune response modulation upon its activation via the oncometabolite succinate. Nonetheless, lit-tle is known about SUCNR1 prognostic relevance and its association with tumor immune infil-trates and microbiota in renal cell carcinoma (RCC). Herein, publicly available platforms in-cluding Human Protein Atlas, cBioPortal, TIMER2, and TISIDB were utilized to depict a diver-gent implication of SUCNR1 in the immune microenvironment of clear cell RCC (KIRC) and pa-pillary RCC (KIRP); the two major subtypes of RCC. Our results showed that SUCNR1 expression level was augmented in RCC compared to other solid cancers, yet with opposite survival rate predictions in RCC subtypes. Consequently, higher expression level of SUCNR1 was associated with a good disease-specific survival rate (p=5.797e-5) in KIRC patients albeit a poor prognostic prediction in KIRP patients (p=1.9282e-3). Intriguingly, SUCNR1 was mainly correlated to im-munomodulators and diverse immune infiltrates in KIRP. Whereas the receptor was mostly asso-ciated with a repertoire of microbes including beneficial bacteria that likely influenced a better disease-specific survival rate in KIRC. Our findings illustrate a significant subtype-specific role of SUCNR1 in RCC which potentially modulates tumor immune infiltration and microbiome sig-nature, hence altering the prognosis of cancer patients.