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The following is a summary of “Role of autophagy dysregulation in low and high-grade nonmuscle invasive bladder cancer: A survival analysis and clinicopathological association,” published in the September 2024 issue of Urology by Kumar et al.

Bladder cancer, which disproportionately affects men, frequently presents as nonmuscle-invasive bladder cancer (NMIBC). Despite initial treatment efforts, NMIBC often recurs or progresses, a phenomenon closely associated with autophagy. This study aimed to evaluate the expression of key autophagy-related genes—mTOR, ULK1, Beclin1, and LC3—in NMIBC and to explore their potential as prognostic markers and therapeutic targets. The researchers analyzed 115 tissue samples, including 85 from patients with NMIBC  (comprising pTa, pT1, and carcinoma in situ [CIS]) and 30 from patients with benign prostatic hyperplasia (BPH) as controls. Gene expression was assessed using quantitative real-time polymerase chain reaction (qRT-PCR), and western blotting measured protein levels. 

Multivariate and univariate survival analyses were conducted using SPSS to correlate gene expression with clinicopathological characteristics. In high-grade NMIBC, investigators observed significant downregulation of ULK1 (P = 0.0150), Beclin1 (P = 0.0041), and LC3 (P = 0.0014), while mTOR was notably upregulated (P = 0.0006). Kaplan-Meier plots indicated significant differences in survival outcomes linked to the expression levels of these autophagy genes. High-grade tumors, advanced tumor stages (CIS, P = 0.039; pT1, P = 0.018), male gender (P = 0.010), and lymphovascular invasion (P = 0.028) were identified as significant risk factors for poorer survival. 

Specifically, the upregulation of mTOR and downregulation of ULK1 and Beclin1 were associated with diminished recurrence-free and progression-free survival in patients with NMIBC. These findings underscore the potential of autophagy-related genes as prognostic biomarkers in NMIBC, offering insights into their role in disease progression and highlighting opportunities for targeted therapeutic strategies.

Source: sciencedirect.com/science/article/abs/pii/S1078143924005702