Somatic alterations of genitourinary malignancy of Chinese population based on tumor NGS data

Genitourinary malignancies represent a major global health burden, with rising incidence and mortality rates, particularly in China. Comprehensive genomic profiling in Chinese patients remains limited. This study aimed to characterize the mutational landscape of genitourinary cancers to identify potential biomarkers for improved diagnosis and treatment.

Tumor tissues from 244 Chinese patients, encompassing 321 samples of bladder, renal, and prostate cancers, were analyzed using next-generation sequencing (NGS) with a 680-gene cancer-specific panel. Somatic mutation profiles were compared across cancer types and with Western (MSK-IMPACT) cohorts.

PD-L1 positivity was observed in 13.89 % of bladder, 10.00 % of renal, and 4.55 % of prostate cancers. Median tumor mutational burden (TMB) was 3.29 mut/Mb for bladder, 2.13 mut/Mb for renal, and 0.66 mut/Mb for prostate cancer. Frequently mutated genes included VHL (20.45 %), TP53 (20.07 %), KMT2D (13.01 %), KMT2C (10.04 %), and TERT (9.67 %). Across tumor types, gene-PD-L1 correlations were modest to moderate. In bladder cancer, TP53 (r = 0.551, FDR = 0.0086) and CCNE1 (r = 0.469, FDR = 0.0338) showed significant positive associations with PD-L1 expression, while AXL and AKT2 were borderline significant. In renal and prostate cancers, AXL, RARA, and LARP4 exhibited weaker yet significant correlations. Comparative analysis with Western cohorts revealed moderate gene overlap (Jaccard ≈ 0.20-0.24) but weak frequency concordance (r < 0.25), indicating population-specific genomic heterogeneity.

This study delineates the genomic landscape of bladder, renal, and prostate cancers in Chinese patients and identifies distinct mutational profiles compared with Western populations, supporting region-tailored precision oncology in genitourinary malignancies.

This study analyzed 321 tumor samples from 244 Chinese patients with genitourinary cancers using targeted NGS. Distinct mutational landscapes and PD-L1-associated genes were identified across bladder, renal, and prostate cancers. Comparative analysis with Western cohorts revealed population-specific genomic heterogeneity, supporting region-tailored precision oncology.