Molecular differences in renal cell carcinoma between males and females

PurposeThe 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.MethodsWe performed a narrative review synthesizing contemporary evidence on sex-specific molecular differences in healthy kidney tissue and RCC.ResultsIn 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.ConclusionCurrent evidence suggests meaningful genomic differences between male and female RCC, highlighting the need for sex-specific RCC research and personalized sex-specific treatment approaches.

Automated summary

The molecular mechanisms underlying the disparity in RCC risk and treatment outcome between males and females are poorly understood. Gene expression differences, especially in sex-chromosome-linked genes, play a significant role in healthy kidney tissue and RCC. The distribution of RCC histologies varies between sexes, and there are pronounced sex-specific gene expressions and pathways in clear-cell and papillary RCC.