Unveiling the role of SRY in male-biased cancers: Insights into the molecular basis of sex disparities in high-grade glioma and melanoma

Publication date: Jul 14, 2023

Sex disparities have been observed in many tumor types affecting non-reproductive organs. Typically, the incidence and mortality rates of such cancers are higher in men. Although differences in lifestyle and environmental exposures are known contributors, knowledge of the molecular mechanisms driving sexual dimorphism in tumor development and therapy response remains limited. To address this question, we comprehensively studied the sex-determining region Y (SRY) gene, a male-specific gene that is critical in development. First, we screened 2,448 samples from 11 cancer types to identify those with a higher incidence in men and increased expression of SRY. In cases of high-grade glioma and melanoma, men with tumors exhibiting high SRY expression had a worse prognosis. Our results suggest that SRY target genes show altered expression when SRY is overexpressed. These gene sets are linked to cell growth, epithelial-mesenchymal transition, inflammation, and repression of tumor suppressor pathways (TP53 activation and activity of immune cells). In summary, we present the first comprehensive investigation of SRY expression and its association with clinical outcomes in men with high-grade glioma and melanoma. Our results shed light on the molecular basis for sex disparities and lay the foundation for investigation of various target genes and novel cancer treatments in men with high-grade glioma and melanoma.


Concepts Keywords
Driving Biorxiv
Forestmodel Expression
July Figure
Tumorigenesis Glioma
Underexpressed Grade


Type Source Name
disease MESH cancers
disease MESH glioma
pathway KEGG Glioma
disease MESH melanoma
pathway KEGG Melanoma
disease MESH lifestyle
disease MESH inflammation
disease MESH repression
disease MESH lung cancer
disease MESH bladder cancer
pathway KEGG Bladder cancer
disease MESH esophageal cancer
disease MESH thyroid cancers
disease MESH abnormalities
disease MESH hepatocellular carcinoma
pathway KEGG Hepatocellular carcinoma
disease MESH skin cancer
disease MESH glioblastoma
disease MESH anaplastic astrocytoma
disease MESH anaplastic oligodendroglioma
disease MESH cognitive impairment
disease MESH seizure disorders
disease MESH carcinoma
disease MESH squamous carcinoma
drug DRUGBANK Topiramate
disease MESH papillary carcinoma
disease MESH adenocarcinoma
drug DRUGBANK Thymidine monophosphate
pathway REACTOME Release
disease MESH metastasis
pathway KEGG Apoptosis
disease MESH tumorigenesis
drug DRUGBANK Estradiol
drug DRUGBANK Somatotropin
disease MESH prostate cancer
pathway KEGG Prostate cancer
disease MESH campomelic dysplasia
disease MESH deformities
disease MESH macrocephaly
disease MESH micrognathia
disease MESH cleft palate
drug DRUGBANK Bismuth subgallate
disease MESH Central Nervous System Tumors

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