Comprehensive Characterization of Molecular Differences in Cancer between Male and Female Patients

An individual's sex has been long recognized as a key factor affecting cancer incidence, prognosis, and treatment responses. However, the molecular basis for sex disparities in cancer remains poorly understood. We performed a comprehensive analysis of molecular differences between male and female patients in 13 cancer types of The Cancer Genome Atlas and revealed two sex-effect groups associated with distinct incidence and mortality profiles. One group contains a small number of sex-affected genes, whereas the other shows much more extensive sex-biased molecular signatures. Importantly, 53% of clinically actionable genes (60/114) show sex-biased signatures. Our study provides a systematic molecular-level understanding of sex effects in diverse cancers and suggests a pressing need to develop sex-specific therapeutic strategies in certain cancer types.

For many cancer types, men and women are very different in terms of susceptibility, survival, and mortality. But our knowledge about the differences between male and female cancer patients at the molecular level is very limited. This is a fundamental issue for cancer prevention and therapy but has not been investigated systematically. Through a rigorous, multidimensional analysis of sex-affected genes, we revealed a two-group molecular classification of cancer types (weak sex-effect group versus strong sex-effect group) and demonstrated that >50% of clinically actionable genes showed sex-biased molecular signatures in certain cancer types. Our study helps elucidate the molecular basis for sex disparities in cancer and lays a critical foundation for the future development of precision cancer medicine.