Sexual dimorphism in cancer: insights from transcriptional signatures in kidney tissue and renal cell carcinoma.

Aged Biomarkers, Tumor / metabolism Carcinoma, Renal Cell / genetics Disease Progression Female Gene Expression Profiling Gene Expression Regulation, Neoplastic Genes, Tumor Suppressor Genes, X-Linked Genetic Association Studies Genetic Predisposition to Disease Genome-Wide Association Study Humans Kidney Neoplasms / genetics Male Middle Aged Prognosis Sex Characteristics

Journal

Human molecular genetics

ISSN: 1460-2083

Titre abrégé: Hum Mol Genet

Pays: England

ID NLM: 9208958

Informations de publication

Date de publication:
27 04 2021

Historique:

received: 18 11 2020

revised: 18 01 2021

accepted: 20 01 2021

pubmed: 3 2 2021

medline: 26 11 2021

entrez: 2 2 2021

Statut: ppublish

Résumé

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.

Identifiants

DOI: 10.1093/hmg/ddab031 PMID: 33527138 PMC: PMC8098110

pubmed: 33527138

pii: 6126014

doi: 10.1093/hmg/ddab031

pmc: PMC8098110

doi:

Substances chimiques

Biomarkers, Tumor 0

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

Pagination

343-355

Subventions

Organisme : Cancer Research UK

ID : 24390

Pays : United Kingdom

Organisme : NCI NIH HHS

ID : U01 CA155309

Pays : United States

Informations de copyright

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