BRCA1-associated protein 1 (BAP1) is a critical cell cycle and DNA damage response regulator. BAP1 is mutated in about 10% of renal cell carcinoma (RCC). In this study, we performed comprehensive in silico analysis to investigate the gender-biased differential role of BAP1 mutation in RCC.

We used the processed data from several public databases (The Cancer Genome Atlas database, AACR GENIE, ICGC, CPTAC, IMmotion 151, JAVELIN RENAL 101, TRACERx, FUSCC, HCRN). We analyzed the gender difference between BAP1 mutation, and clinicopathological findings and prognosis. all mutation types (missense, truncating, splice, and other mutation types) were considered “mutated type”

AACR GENIE cohort showed that the rate of BAP1 mutation was significantly higher in females than males. BAP1 mutation was significantly associated with metastasis and sarcomatoid histology in females, not in males in several cohorts. The female patients with BAP1 mutation had a poor prognosis compared to those with wild type in several cohorts. The females with BAP1 mutation had a poor prognosis compared to those with wild type in patients with sunitinib treatment from IMmotion 151. Males with BAP1 mutation had a favorable prognosis compared to those with wild type treated with avelumab and axitinib in the JAVELIN RENAL 101 cohort (Figure 1). However, there was no significant difference in prognosis in females according to BAP1 mutation (Figure 2).

The ratio of BAP1 mutation was higher in females than in males. The effect of BAP1 mutation on sunitinib and the combination treatment (avelumab + axitinib) varied according to gender. These findings may contribute to precision medicine in RCC.