Sexual dimorphism in cancer: insights from transcriptional signatures in kidney tissue and renal cell carcinoma. Issue 5 (2nd February 2021)

• Record Type: Journal Article
• Authors: Laskar, Ruhina S; Li, Peng; Ecsedi, Szilvia; Abedi-Ardekani, Behnoush; Durand, Geoffroy; Robinot, Nivonirina; Hubert, Jean-Noël; Janout, Vladimir; Zaridze, David; Mukeria, Anush; Mates, Dana; Holcatova, Ivana; Foretova, Lenka; Swiatkowska, Beata; Dzamic, Zoran; Milosavljevic, Sasa; Olaso, Robert; Boland, Anne; Deleuze, Jean-François; Muller, David C; McKay, James D; Brennan, Paul; Le Calvez-Kelm, Florence; Scelo, Ghislaine; Chanudet, Estelle
• Is Part Of: Human molecular genetics. Volume 30:Issue 5(2021)
• Page Start: 343
• Page End: 355
• Publication Date: 2021-02-02
• Subjects: Human molecular genetics -- Periodicals; Human chromosome abnormalities -- Periodicals; 572.8
• DOI: 10.1093/hmg/ddab031
• Languages: English
• ISSNs: 0964-6906

Abstract

Abstract: 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.