Conclusion
Our findings offer preliminary clinical evidence accentuating KDM6A alterations as a promising prognostic and predictive biomarker while elucidating the gender disparities observed in patients with UC.
Objective
KDM6A, a representative tumour suppressor gene with sex bias, is frequently altered in urothelial carcinoma (UC). The specific impacts of KDM6A mutations on gender-based clinical outcomes in UC remain poorly understood.
Results
KDM6A 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. KDM6A 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, KDM6A Mut male patients displayed the most favourable clinical outcomes, whereas KDM6A Mut female patients demonstrated the least favourable outcomes. Independent of gender variations, KDM6A Mut patients exhibited heightened androgen receptor and diminished oestrogen receptor 1 filtered regulon activity. Additionally, KDM6A Mut male patients showed increased infiltration of T cells, cytotoxic T cells and NK cells with enriched neoantigens, in contrast to KDM6A Mut female patients who manifested a more pronounced angiogenesis signature.