STAG2 Coupled With p53 Alteration Has a Significant Impact on Bladder Cancer Recurrence and Progression

Abstract Background:There is an unmet need for additional biomarkers for stratifying tumors based on their risk of recurrence and progression. Stromal antigen 2 (STAG2) and p53 are the most common mutations in bladder cancer and their association with the prognosis of bladder cancer remains unclear. Methods: Patients were divided into two cohorts according to stage and surgical procedure. The value of combined STAG2 expression (+/-) and P53 mutation (+/-) was evaluated for prediction of recurrence in 334 patients diagnosed by transurethral resection of bladder tumor (TURBT) and for prediction of survival in 144 patients who underwent radical cystectomy and pelvic lymphadenectomy( RCPLT). Results: We found that,in the 334 TURBT-treated patients, recurrence rate was significantly greater for STAG2(+) tumors than STAG2(-) tumors (73.5% vs. 55.0%, P=0.001). Of 144 RCPLT-treated patients, 127 (88.2%) were STAG2(+), of which 71 (55.9%) survived 5 years, compared to none of the 17 STAG2(-) patients. Patients with combined STAG2(+)/P53 mutation(+) tumors had the highest recurrence rate (83.5%) while patients with STAG2(-)/P53(-) tumors had the lowest recurrence rate (50%). Patients with STAG2(+)/P53(-) tumors achieved the highest 5-year survival rate (69.7%). Systemic chemotherapy did not improve prognosis of RCPLT-treated patients, but appeared to benefit STAG2(-) patients. Conclusions: Our results suggest that combined STAG2 expression and P53 status is a valuable biomarker for BCa prognosis, accurately predicting recurrence in TURBT-treated patients. STAG2(+)/P53(-) predicted a higher five-year survival and STAG2(-) predicted low five-year survival in RCPLT-treated patients. Chemotherapy may interfere with this predictive efficacy, especially in STAG2(-) patients.