Sexual dimorphism in cancer: insights from transcriptional signatures in kidney tissue and renal cell carcinoma
| Autor: | 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 |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
AcademicSubjects/SCI01140
Male Sex Characteristics Gene Expression Profiling Middle Aged Prognosis Kidney Neoplasms Gene Expression Regulation Neoplastic Genes X-Linked Biomarkers Tumor Disease Progression Humans Female Genes Tumor Suppressor Genetic Predisposition to Disease General Article Carcinoma Renal Cell Genetic Association Studies Aged Genome-Wide Association Study |
| Zdroj: | Human Molecular Genetics |
| ISSN: | 1460-2083 0964-6906 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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