biostudies-literatureLaskar RSUS National Institutes of HealthCancer Research UKWorld Health OrganizationAgence Nationale pour la RechercheNational Cancer InstituteNCI NIH HHS343-355https://www.ebi.ac.uk/biostudies/studies/S-EPMC8098110biostudies-literatureUnknown30(5)Sexual dimorphism in cancer incidence and outcome is widespread. Understanding the underlying mechanisms is fundamental to improve cancer prevention and clinical management. Sex disparities are particularly striking in kidney cancer: across diverse populations, men consistently show unexplained 2-fold increased incidence and worse prognosis. We have characterized genome-wide expression and regulatory networks of 609 renal tumors and 256 non-tumor renal tissues. Normal kidney displayed sex-specific transcriptional signatures, including higher expression of X-linked tumor suppressor genes in women. Sex-dependent genotype-phenotype associations unraveled women-specific immune regulation. Sex differences were markedly expanded in tumors, with male-biased expression of key genes implicated in metabolism, non-malignant diseases with male predominance and carcinogenesis, including markers of tumor infiltrating leukocytes. Analysis of sex-dependent RCC progression and survival uncovered prognostic markers involved in immune response and oxygen homeostasis. In summary, human kidney tissues display remarkable sexual dimorphism at the molecular level. Sex-specific transcriptional signatures further shape renal cancer, with relevance for clinical management.Human molecular geneticsSexual dimorphism in cancer: insights from transcriptional signatures in kidney tissue and renal cell carcinoma.PMC809811024390001ANR-10-INBS-09U01 CA155309U01CA155309Robinot NMukeria ADzamic ZScelo GChanudet EMates DHolcatova IBoland AForetova LHubert JNAbedi-Ardekani BMcKay JDBrennan PMuller DCDurand GLe Calvez-Kelm FLi PSwiatkowska BLaskar RSDeleuze JFJanout VOlaso RMilosavljevic SZaridze DEcsedi SfalseSexual dimorphism in cancer: insights from transcriptional signatures in kidney tissue and renal cell carcinoma.Sexual dimorphism in cancer incidence and outcome is widespread. Understanding the underlying mechanisms is fundamental to improve cancer prevention and clinical management. Sex disparities are particularly striking in kidney cancer: across diverse populations, men consistently show unexplained 2-fold increased incidence and worse prognosis. We have characterized genome-wide expression and regulatory networks of 609 renal tumors and 256 non-tumor renal tissues. Normal kidney displayed sex-specific transcriptional signatures, including higher expression of X-linked tumor suppressor genes in women. Sex-dependent genotype-phenotype associations unraveled women-specific immune regulation. Sex differences were markedly expanded in tumors, with male-biased expression of key genes implicated in metabolism, non-malignant diseases with male predominance and carcinogenesis, including markers of tumor infiltrating leukocytes. Analysis of sex-dependent RCC progression and survival uncovered prognostic markers involved in immune response and oxygen homeostasis. In summary, human kidney tissues display remarkable sexual dimorphism at the molecular level. Sex-specific transcriptional signatures further shape renal cancer, with relevance for clinical management.2021-01-01T00:00:00Z2021 Apr2026-04-18T05:22:29.054Z2024-11-21T08:14:23.463ZS-EPMC80981103352713810.1093/hmg/ddab031