Molecular differences in renal cell carcinoma between males and females

The disparity in renal cell carcinoma (RCC) risk and treatment outcome between males and females is well documented, but the underlying molecular mechanisms remain poorly elucidated.

We performed a narrative review synthesizing contemporary evidence on sex-specific molecular differences in healthy kidney tissue and RCC.

In healthy kidney tissue, gene expression differs significantly between males and females, including autosomal and sex-chromosome-linked genes. The differences are most prominent for sex-chromosome-linked genes and attributable to Escape from X chromosome-linked inactivation and Y chromosome loss. The frequency distribution of RCC histologies varies between the sexes, particularly for papillary, chromophobe, and translocation RCC. In clear-cell and papillary RCC, sex-specific gene expressions are pronounced, and some of these genes are amenable to pharmacotherapy. However, for many, the impact on tumorigenesis remains poorly understood. In clear-cell RCC, molecular subtypes and gene expression pathways have distinct sex-specific trends, which also apply to the expression of genes implicated in tumor progression.

Current evidence suggests meaningful genomic differences between male and female RCC, highlighting the need for sex-specific RCC research and personalized sex-specific treatment approaches.