Identification and Analysis of Sex-Biased Copy Number Alterations

Background: Sex difference has long been recognized at cancer incidence, outcomes, and responses to therapy. Analyzing the somatic mutation profiles of large-scale cancer samples between the sexes have revealed several potential drivers of cancer with sex difference. However, it is still a demand fo...

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Bibliographic Details
Main Authors: Chenhao Zhang, Yang Yang, Qinghua Cui, Dongyu Zhao, Chunmei Cui
Format: Article
Language:English
Published: American Association for the Advancement of Science (AAAS) 2024-01-01
Series:Health Data Science
Online Access:https://spj.science.org/doi/10.34133/hds.0121
Description
Summary:Background: Sex difference has long been recognized at cancer incidence, outcomes, and responses to therapy. Analyzing the somatic mutation profiles of large-scale cancer samples between the sexes have revealed several potential drivers of cancer with sex difference. However, it is still a demand for in-depth scrutinizing the sex-biased characteristics of genome instability to link the clinical differences for individual cancer type. Methods: Here, we utilized a published framework devised to specifically compare the copy number profiles between 2 groups to identify the sex-biased copy number alterations (CNAs) across 16 cancer types from the The Cancer Genome Atlas Program database, and dissected the impact of those CNAs. Results: Totally, 81 male-biased CNA regions and 23 female-biased CNA regions in 16 cancer types were found. Functional annotation analysis showed that several critical biological functions associated with sex-biased CNAs are shared in multiple cancer types, including immune-related pathways and regulation of cellular signaling. Most sex-biased CNAs have a substantial effect on transcriptional consequence, where the average of over 68% of genes have a linear relationship with CNAs across cancer types, and 14% of those genes are affected by the combination of the sex and copy number. Furthermore, 29 sex-biased CNA regions show latent capacity to be sex-specific prognostic biomarker such as CNA on 11q13.4 for head and neck cancer and lung cancer. Conclusions: This analysis offers new insights into the role of sex in cancer etiology and prognosis through a detailed characterization of sex differences in genome instability of diverse cancers.
ISSN:2765-8783