Mitochondrial Aldehyde Dehydrogenase 2 Represents a Potential Biomarker of Biochemical Recurrence in Prostate Cancer Patients

Abstract

Background: We aimed to explore the role of mitochondrial aldehyde dehydrogenase 2 (ALDH2) in prostate cancer (PCa) patients and provide insights into the tumor immune microenvironment (TME) for those patients undergoing radical radiotherapy. Methods: We performed all analyses using R version 3.6.3 and its suitable packages. Cytoscape 3.8.2 was used to establish network of competing endogenous RNAs (ceRNAs). Results: Downregulation of ADLH2 was significantly associated with higher risk of BCR-free survival (HR: 0.40, 95%CI: 0.24–0.68, p = 0.001) and metastasis-free survival (HR: 0.21, 95%CI: 0.09–0.49, p = 0.002). Additionally, ALDH2 repression contributed to significantly shorter BCR-free survival in the TCGA database (HR: 0.55, 95%CI: 0.33–0.93, p = 0.027). For immune checkpoints, patients that expressed a higher level of CD96 had a higher risk of BCR than their counterparts (HR: 1.79, 95%CI: 1.06–3.03, p = 0.032), as well as NRP1 (HR: 2.18, 95%CI: 1.29–3.69, p = 0.005). In terms of the TME parameters, the spearman analysis showed that ALDH was positively associated with B cells (r: 0.13), CD8+ T cells (r: 0.19), neutrophils (r: 0.13), and macrophages (r: 0.17). Patients with higher score of neutrophils (HR: 1.75, 95%CI: 1.03–2.95, p = 0.038), immune score (HR: 1.92, 95%CI: 1.14–3.25, p = 0.017), stromal score (HR: 2.52, 95%CI: 1.49–4.26, p = 0.001), and estimate score (HR: 1.81, 95%CI: 1.07–3.06, p = 0.028) had higher risk of BCR than their counterparts. Our ceRNA network found that PART1 might regulate the expression of ALDH via has-miR-578 and has-miR-6833-3p. Besides, PHA-793887, PI-103, and piperlongumine had better correlations with ALDH2. Conclusions: We found that ALDH2 might serve as a potential biomarker predicting biochemical recurrence for PCa patients.