Abstract
Introduction: The aim of this study was to evaluate the expression of SIRT7 in upper tract urothelial carcinoma (UTUC) as well as the predictive value for prognosis in patients undergoing radical nephroureterectomy followed platinum-based adjuvant chemotherapy. Methods: Pathological samples of 146 UTUC with clinical stage T2 and above undergoing radical nephrectomy (RNU) were collected. All patients received adjuvant cisplatin-based chemotherapy and 40 UTUC patients received second-line immunotherapy after disease progression. The relationship between the expression level of SIRT7 by immunohistochemistry and clinicopathological characteristics, disease-free survival (DFS), overall survival (OS), and OS after progression (POS) was analyzed. Results: Over a mean follow-up 47 months, 61 (41.8%) patients experienced recurrence and 42 (28.8%) patients died due to UTUC. The results revealed that 70.2% of UTUC tissue samples exhibited high expression levels of SIRT7. High expression of SIRT7 is associated with lymph node metastasis (p < 0.001), lymphovascular invasion (p = 0.001), and histological differentiation (p = 0.025). In addition, UTUC patients with elevated SIRT7 expression experienced significantly shorter DFS (hazard ratio [HR] 3.760, 95% CI: 1.884–7.504, p < 0.001 and OS (HR 2.706, 95% CI: 1.235–5.929, p = 0.013). Multivariate analyses demonstrated that SIRT7 served as a significant predictor for DFS (HR 2.337, 95% CI: 1.117–4.890, p = 0.024) in UTUC patients. Furthermore, we found SIRT7 high expression is associated with prolonged POS in patients progressed after adjuvant cisplatin-based chemotherapy and received second-line immunotherapy. Conclusion: SIRT7 is an independent prognostic marker of poor DFS in locally advanced UTUC patients after RNU. Moreover, these data suggest that SIRT7 could potentially serve as a target for assessing the efficacy of chemotherapy and immunotherapy in UTUC.
