Gender disparities in clinical outcomes of urothelial carcinoma linked to X chromosome gene mutation.

OBJECTIVE

, a representative tumour suppressor gene with sex bias, is frequently altered in urothelial carcinoma (UC). The specific impacts of mutations on gender-based clinical outcomes in UC remain poorly understood.

METHODS AND ANALYSIS

We enrolled 2438 patients with UC from seven independent real-world cohorts possessing comprehensive clinical and genomic data. Point mutations and homozygous deletions of are categorised as . We assessed the correlation between gender disparities in relation to status and clinical outcomes, as well as genomic and immunological profiles.

RESULTS

mutations were identified in 679 of the 2306 patients with UC (29.4%), with 505 of 1768 (28.6%) in men and 174 of 538 (32.3%) in women. mutations correlated with enhanced overall survival exclusively in male patients but were linked to improved outcomes following adjuvant chemotherapy only in female patients. Concerning immunotherapeutic responses, male patients displayed the most favourable clinical outcomes, whereas female patients demonstrated the least favourable outcomes. Independent of gender variations, patients exhibited heightened androgen receptor and diminished oestrogen receptor 1 filtered regulon activity. Additionally, male patients showed increased infiltration of T cells, cytotoxic T cells and NK cells with enriched neoantigens, in contrast to female patients who manifested a more pronounced angiogenesis signature.

CONCLUSION

Our findings offer preliminary clinical evidence accentuating alterations as a promising prognostic and predictive biomarker while elucidating the gender disparities observed in patients with UC.