RSUME (RWD domain-containing protein SUMO Enhancer), RWD domain containing 3 (RWDD3) gene product, is upregulated by hypoxia and expressed in organs prone to develop von Hippel-Lindau (VHL) syndrome tumors.
We evaluated RSUME prognostic value in clear cell renal cell carcinoma (ccRCC) based mainly on the dataset (KIRC) from patients in The Cancer Genome Atlas (TCGA). Wilcoxon signed-rank test and one-way analysis of variance (ANOVA) followed by Tukey's test were used to evaluate relationships between clinicopathological features and RSUME expression and univariate and multivariate Cox regression analysis methods were used to evaluate prognostic factors. The biological function of RSUME was assessed by gene set enrichment analysis (GSEA). For validation, total amount of ROS was detected in ccRCC cell lines using dichlorofluorescin diacetate.
RSUME is highly expressed in tumor tissues compared with normal tissues (P = .006, P = .039, P = .002, P = .036, P < .001) and associates with tumor T (P = .018) and tumor M (P = .036) advanced stages and higher extent cysts (P = .005). RSUME expression appears to be an independent risk factor for overall survival (OS) (P = .002) and disease-specific survival (DSS) (P = .026) in ccRCC patients. GSEA showed enrichment of relevant glycerophospholipid- and ROS-related pathways in RSUME high-expression phenotype. ROS diminished levels in RSUME-silenced ccRCC cell lines validated RSUME relevance in ROS-related pathways.
RSUME high expression may predict poor prognosis in ccRCC and impact through its action on metabolism and ROS related pathways.
Clinical genitourinary cancer. 2023 Mar 24 [Epub ahead of print]
David Gonilski-Pacin, Nicolas Ciancio Del Giudice, Belen Elguero, Eduardo Arzt
Instituto de Investigación en Biomedicina de Buenos Aires (IBioBA) - CONICET - Partner Institute of the Max Planck Society, Buenos Aires, Argentina., Instituto de Investigación en Biomedicina de Buenos Aires (IBioBA) - CONICET - Partner Institute of the Max Planck Society, Buenos Aires, Argentina; Departamento de Fisiología y Biología Molecular y Celular, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina. Electronic address: .
PubMed http://www.ncbi.nlm.nih.gov/pubmed/37059686