Zhang Jingxin
The First Clinical Medical College, Xuzhou Medical University, Xuzhou, Jiangsu, China.
Sci Rep. 2025 Jul 4;15(1):23933. doi: 10.1038/s41598-025-07818-5.
Prohibitin2 (PHB2) is a mitochondrial endosomal protein that is closely linked to tumors; however, its specific molecular role remains unclear. Therefore, this study investigates the role of PHB2 in cancer. Multiple databases, including cBioPortal, PhosphoNET, and AlphaFold, were accessed to investigate this issue. The findings indicated that PHB2 expression in tumor tissues exceeded that in normal tissues, with PHB2 localized in mitochondria. Patients diagnosed with bladder and lung adenocarcinomas exhibiting elevated PHB2 expression demonstrated an increased survival rate compared to those with reduced expression levels. Conversely, the opposite was observed in patients with renal clear cell carcinoma and breast cancer. In pan-cancer, the mutation rate of PHB2 was elevated, with several overlapping amino acid sites exhibiting tumor mutations and post-translational modifications, including phosphorylation at tyrosine 121, acetylation at threonine 263, and ubiquitination at lysine 296. Multiple overlapping sites of amino acid phosphorylation modifications and mutations were identified in PHB2, specifically at threonine 42, tyrosine 121, and threonine 263. The three-dimensional predicted structure of PHB2 was analyzed utilizing the AlphaFold database. The pathogenicity mutation heatmap indicated that the overlapping sites of amino acid mutations and post-translational modifications, including phosphorylation (threonine 42, tyrosine 121, and threonine 263), acetylation, and ubiquitination (lysine 296), were significantly pathogenic. In conclusion, PHB2 exhibits cancer-type-specific prognostic associations. Its overlapping mutation and modification sites suggest potential functional importance, supporting its role as a candidate biomarker for further validation in pan-cancer contexts.
prohibitin2（PHB2）是一种线粒体内涵体蛋白，与肿瘤密切相关；然而，其具体分子作用仍不清楚。因此，本研究调查了PHB2在癌症中的作用。通过访问包括cBioPortal、PhosphoNET和AlphaFold在内的多个数据库来研究这个问题。研究结果表明，肿瘤组织中PHB2的表达超过正常组织，且PHB2定位于线粒体。被诊断为膀胱和肺腺癌且PHB2表达升高的患者与表达水平降低的患者相比，生存率有所提高。相反，在肾透明细胞癌和乳腺癌患者中观察到相反的情况。在泛癌中，PHB2的突变率升高，有几个重叠的氨基酸位点表现出肿瘤突变和翻译后修饰，包括酪氨酸121磷酸化、苏氨酸263乙酰化和赖氨酸296泛素化。在PHB2中鉴定出多个氨基酸磷酸化修饰和突变的重叠位点，特别是在苏氨酸42、酪氨酸121和苏氨酸263处。利用AlphaFold数据库分析了PHB2的三维预测结构。致病性突变热图表明，氨基酸突变和翻译后修饰的重叠位点，包括磷酸化（苏氨酸42、酪氨酸121和苏氨酸263）、乙酰化和泛素化（赖氨酸296），具有显著致病性。总之，PHB2表现出癌症类型特异性的预后关联。其重叠的突变和修饰位点表明其潜在的功能重要性，支持其作为候选生物标志物在泛癌背景下进一步验证的作用。
