Di Yancheng, Zhao Linlin, Zhang Lingling, Chen Lei
Department of Urology, Hongqi Hospital Affiliated to Mudanjiang Medical University, No. 5 Tongxiang Road, Aimin District, Mudanjiang, 157000, China.
Hum Cell. 2025 Jun 23;38(4):120. doi: 10.1007/s13577-025-01249-0.
Prostate cancer is the second leading cause of cancer-related deaths in males that has an unfavorable outcome. Autophagy-related genes (ARGs) contribute to the process of tumorigenesis and metastasis of prostate cancer. This study aimed to identify ARGs that could serve as reliable and non-invasive biomarkers for evaluating prostate cancer prognosis. The expression profiles of ARGs were identified in prostate cancer specimens with good prognosis (n = 98) and poor prognosis (n = 42). A series of in vitro assays were performed to explore the function and mechanisms of ARGs in malignant progression of prostate cancer. Receiver operating characteristic curve were utilized to evaluate the predictive potential of ARGs for prostate cancer prognosis. Patients with poor prognosis exhibited higher expression of baculoviral inhibitor of apoptosis repeat containing 5 (BIRC5) and lower expression of neuregulin 2 (NRG2) compared to those with good prognosis. BIRC5 served as independent risk factors for prostate cancer prognosis, and enhanced BIRC5 expression promoted cells viability, migration, and invasion, but the autophagy activator rapamycin could counteract the effects of the BIRC5 gene. Conversely, NRG2 acted as a protective factor for prostate cancer prognosis, and elevated NRG2 expression suppressed cells viability, migration, and invasion, but the autophagy inhibitor 3-Methyladenine could reverse the effects of the NRG2 gene. The combination of BIRC5, NRG2 with prostate specific antigen (PSA) demonstrated significant predictive value for prostate cancer prognosis. BIRC5 and NRG2 genes participate in the progression of prostate cancer by regulating autophagy. BIRC5 and NRG2 have the potential to serve as valuable biomarkers for the prognosis of prostate cancer.
前列腺癌是男性癌症相关死亡的第二大主要原因,其预后不佳。自噬相关基因(ARGs)有助于前列腺癌的肿瘤发生和转移过程。本研究旨在鉴定可作为评估前列腺癌预后的可靠且非侵入性生物标志物的ARGs。在预后良好(n = 98)和预后不良(n = 42)的前列腺癌标本中鉴定ARGs的表达谱。进行了一系列体外试验以探讨ARGs在前列腺癌恶性进展中的功能和机制。利用受试者工作特征曲线评估ARGs对前列腺癌预后的预测潜力。与预后良好的患者相比,预后不良的患者凋亡重复序列包含蛋白5(BIRC5)表达较高,神经调节蛋白2(NRG2)表达较低。BIRC5是前列腺癌预后的独立危险因素,增强的BIRC5表达促进细胞活力、迁移和侵袭,但自噬激活剂雷帕霉素可抵消BIRC5基因的作用。相反,NRG2是前列腺癌预后的保护因素,升高的NRG2表达抑制细胞活力、迁移和侵袭,但自噬抑制剂3-甲基腺嘌呤可逆转NRG2基因的作用。BIRC5、NRG2与前列腺特异性抗原(PSA)的联合对前列腺癌预后具有显著的预测价值。BIRC5和NRG2基因通过调节自噬参与前列腺癌的进展。BIRC5和NRG2有潜力作为前列腺癌预后的有价值生物标志物。