Wang Yuan, Chen Ronghui, Jiang Feng-Le, Jiang Xin, Zhou Yuehong, Zhou Yingying, Hong Xinyi, Lin Chaoying, Wang Wei-Jia, Qiu Sufang
The school of Medicine, University of Electronic Science and Technology of China, Chengdu, China.
Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital (Fujian Branch of Fudan University Shanghai Cancer Center), Fuzhou, China.
Front Genet. 2025 Jan 6;15:1515045. doi: 10.3389/fgene.2024.1515045. eCollection 2024.
Prostate cancer (PCa) is a common and serious health issue among older men globally. Metabolic reprogramming, particularly involving lactate and mitochondria, plays a key role in PCa progression, but studies linking these factors to prognosis are limited. To identify novel prognostic markers of PCa based on lactate-mitochondria-related genes (LMRGs), RNA sequencing data and clinical information of PCa from The Cancer Genome Atlas (TCGA) and the cBioPortal database were used to construct a lactate-mitochondria-related risk signature. Here, we established a novel nine-LMRG risk signature for PCa, and Kaplan-Meier curves confirmed a worse prognosis for high-risk subgroups in the TCGA dataset. Meanwhile, a nomogram that effectively predicts the prognosis of PCa patients was also constructed. Next, close associations between the lactate-mitochondria-related signature and the immune microenvironment were examined to clarify the role of LMRGs in shaping the immune landscape. Furthermore, as the only lactate-related gene among the nine key prognostic risk genes, myeloperoxidase (MPO) was identified as a key factor that mediates lactate production and through attenuation of the glycolytic pathway. More importantly, MPO significantly inhibited PCa cell migration, invasion, and epithelial-mesenchymal transition (EMT), indicating its potential as an anticancer gene. Additionally, PCa with high MPO expression is highly sensitive to chemotherapeutic agents and mitochondrial inhibitors, highlighting its potential as an improved therapeutic strategy for PCa management.
前列腺癌（PCa）是全球老年男性中常见且严重的健康问题。代谢重编程，尤其是涉及乳酸和线粒体的代谢重编程，在前列腺癌进展中起关键作用，但将这些因素与预后联系起来的研究有限。为了基于乳酸-线粒体相关基因（LMRGs）确定前列腺癌的新型预后标志物，利用来自癌症基因组图谱（TCGA）和cBioPortal数据库的前列腺癌RNA测序数据和临床信息构建了乳酸-线粒体相关风险特征。在此，我们建立了一种新的前列腺癌九LMRG风险特征，Kaplan-Meier曲线证实了TCGA数据集中高危亚组的预后较差。同时，还构建了一个能有效预测前列腺癌患者预后的列线图。接下来，研究了乳酸-线粒体相关特征与免疫微环境之间的密切关联，以阐明LMRGs在塑造免疫格局中的作用。此外，作为九个关键预后风险基因中唯一与乳酸相关的基因，髓过氧化物酶（MPO）被确定为介导乳酸产生并通过减弱糖酵解途径的关键因素。更重要的是，MPO显著抑制前列腺癌细胞的迁移、侵袭和上皮-间质转化（EMT），表明其作为抗癌基因的潜力。此外，MPO高表达的前列腺癌对化疗药物和线粒体抑制剂高度敏感，突出了其作为改善前列腺癌治疗策略的潜力。
