RSUME IS AN ADVERSE PROGNOSTIC FACTOR IN RENAL CELL CARCINOMA: INVOLVEMENT OF ROS AND CILIA RELATED PATHWAYS

DAVID GONILSKI-PACIN; NICOLAS CIANCIO DEL GIUDICE; BELEN ELGUERO; EDUARDO ARZT

Mar del plata

Congreso; REUNIÓN CONJUNTA SAIC SAI&FAIC SAFIS 2022; 2022

SOCIEDAD ARGENTINA DE INVESTIGACIÓN CLÍNICA (SAIC)

RSUME or RWDD3 is involved in tumor angiogenesis, is upregulated by hypoxia and acts as a negative regulator of VHL protein function in normoxia promoting Hypoxia-inducible factor alpha (HIF-α)stabilization. We evaluated RSUME prognostic value in clear cellRenal Cell Carcinoma (ccRCC) based mainly on the dataset (KIRC)from patients in The Cancer Genome Atlas (TCGA). Wilcoxonsigned-rank test and One-way analysis of variance (ANOVA) followed by Tukey’s test were used to evaluate relationships betweenclinical-pathologic features and RSUME expression. Univariate andmultivariate Cox regression analysis methods were used to evaluatefactors contributing to prognosis. The biological function of RSUMEwas assessed by gene set enrichment analysis (GSEA) and experimentally validated in RCC-786-O cell silenced for RSUME cell lines.High RSUME expression is associated with poor patients’ outcome.It is highly expressed in tumor tissues compared with normal tissues (P = 0.006, P = 0.039, P = 0.002, P = 0.036, P < 0.001) andassociates with tumor T (P = 0.014) and tumor M (P = 0.036) advanced stages and higher extent cysts (P = 0.005). Kaplan-Meiercurves and log-rank tests showed that high RSUME expression isassociated with a short Overall Survival (OS) (P < 0.001) and poorDisease-Free Survival (DFS) (P = 0.021). GSEA showed the enrichment of several pathways, among them Glycerophospholipid metabolism, Cilium and ROS related pathways in RSUME high-expression phenotype. RSUME association with ROS and Cilium pathwayswere assess in RCC-786-O cell silenced for RSUME cell lines. Byusing dichlorofluorescin diacetate (DCFDA) we observed RSUMEsilencing diminishes ROS levels and also diminishes AURKA, OFD1and NPHP3, cilia related genes, validating our in silico results.In summary, RSUME high expression predicts poor prognosis inccRCC and may impact through its action on metabolism, ROS andcilium related pathways. Supported by ANPCyT, CONICET, UBAand FOCEM (COF 03/11).