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In cancer, sex is associated with incidence, progression and therapeutic response, as well as characteristics of the tumour genome and transcriptome. The extent to which sex differences impact the cancer proteome remains largely unknown. To fill this gap, we quantified sex differences across 1,590 proteomes from eight cancer types, identifying 901 genes with sex-differential proteins abundance in adenocarcinomas of the lung, and 20 genes across five other tumour types: squamous cell carcinoma of the lung, hepatocellular carcinomas, clear cell cancers of the kidney, adenocarcinomas of the pancreas and glioblastoma. A subset of these protein differences could be rationalized by sex-differential copy number aberrations. Pathway analysis showed that male-biased proteins in lung adenocarcinoma were enriched in MYC and E2F target pathways. These findings highlight the modest impact of sex on the cancer proteome, but the very limited power of existing proteomics cohorts for these analyses.<\/jats:p>","DOI":"10.1101\/2025.03.14.643396","type":"posted-content","created":{"date-parts":[[2025,3,19]],"date-time":"2025-03-19T16:42:09Z","timestamp":1742402529000},"source":"Crossref","is-referenced-by-count":1,"title":["Sex Differences in the Cancer Proteome"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1674-4533","authenticated-orcid":false,"given":"Chenghao","family":"Zhu","sequence":"first","affiliation":[{"name":"Department of Human Genetics, University of California, Los Angeles, CA, USA"},{"name":"Department of Urology, University of California, Los Angeles, CA, USA"},{"name":"Jonsson Comprehensive Cancer Center, University of California, Los Angeles, CA, USA"},{"name":"Institute for Precision Health, University of California, Los Angeles, CA, USA"},{"name":"Broad Stem Cell Research Center, 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