Huangfu Xuejun, Fan Zhiqiang, Zheng Jia, Xie Jiabei
Department of Urology, Henan Provincial People's Hospital, No.7, Weifu Road, Jinshui District, Zhengzhou, 450003, Henan, China.
Department of Gastroenterology, Henan Provincial People's Hospital, Zhengzhou, 450003, China.
Discov Oncol. 2025 Aug 18;16(1):1579. doi: 10.1007/s12672-025-03215-6.
Mitochondrial dynamics, particularly the balance between fission and fusion, play a crucial role in cancer progression, including prostate cancer, by influencing cellular metabolism and survival. MTFP1 and MTFP2 are key regulators of mitochondrial fission, and their roles in prostate cancer warrant further investigation.
We conducted a comprehensive bioinformatics analysis using RNA-seq data from The Cancer Genome Atlas (TCGA) and SNP data from the UK Biobank (ukb-b-13348) GWAS dataset. Differential gene expression analysis was performed using the limma package, and pathway enrichment analysis was conducted using clusterProfiler. Hub genes were ranked using the CytoHubba algorithms. MCC was prioritized due to its robustness in identifying fully connected subgraphs. Mendelian Randomization (MR) analysis was performed using the TwoSampleMR package to assess the causal relationships between identified hub genes and prostate cancer.
The analysis revealed significant differential expression of MTFP1 and MTFP2 between tumor and adjacent normal tissues, with MTFP2 showing a highly significant upregulation (p-value = 7.06e-06) and an AUC of 0.698, suggesting its potential as a biomarker. In the MR analysis, several hub genes, including ANLN, CDC45, CDCA2, and KIF15, were identified as having a significant causal relationship with prostate cancer, with effect estimates ranging from - 0.03 to 0.15 and statistically significant p-values. These findings suggest that mitochondrial dynamics and related pathways play a critical role in prostate cancer pathogenesis.
The study highlights the potential diagnostic and prognostic value of mitochondrial fission-related genes, particularly MTFP2, in prostate cancer and underscores the importance of further investigating these pathways as therapeutic targets.
线粒体动力学，尤其是裂变与融合之间的平衡，通过影响细胞代谢和存活，在包括前列腺癌在内的癌症进展中发挥关键作用。MTFP1和MTFP2是线粒体裂变的关键调节因子，它们在前列腺癌中的作用值得进一步研究。
我们使用来自癌症基因组图谱（TCGA）的RNA测序数据和来自英国生物银行（ukb-b-13348）全基因组关联研究（GWAS）数据集的单核苷酸多态性（SNP）数据进行了全面的生物信息学分析。使用limma软件包进行差异基因表达分析，使用clusterProfiler进行通路富集分析。使用CytoHubba算法对枢纽基因进行排名。由于MCC在识别完全连通子图方面的稳健性，将其作为优先考虑对象。使用TwoSampleMR软件包进行孟德尔随机化（MR）分析，以评估已识别的枢纽基因与前列腺癌之间的因果关系。
分析显示，MTFP1和MTFP2在肿瘤组织与相邻正常组织之间存在显著差异表达，MTFP2表现出高度显著的上调（p值 = 7.06×10⁻⁶），曲线下面积（AUC）为0.698，表明其作为生物标志物的潜力。在MR分析中，包括ANLN、CDC45、CDCA2和KIF15在内的几个枢纽基因被确定与前列腺癌存在显著因果关系，效应估计值在 - 0.03至0.15之间，p值具有统计学意义。这些发现表明线粒体动力学及相关通路在前列腺癌发病机制中起关键作用。
该研究突出了线粒体裂变相关基因，特别是MTFP2，在前列腺癌中的潜在诊断和预后价值，并强调了进一步研究这些通路作为治疗靶点的重要性。
