Wang Yan, Xu Nuo, Ndzie Noah Marie Louise, Chen Liang, Zhan Xianquan
Department of Gynecological Oncology, Shandong Cancer Institute, Shandong First Medical University & Shandong Academy of Medical Sciences, 440 Jiyan Road, Jinan 250117, China.
Shandong Provincial Key Laboratory of Precision Oncology, Shandong Cancer Institute, Shandong First Medical University & Shandong Academy of Medical Sciences, 440 Jiyan Road, Jinan 250117, China.
Metabolites. 2025 Mar 16;15(3):203. doi: 10.3390/metabo15030203.
Ovarian cancer (OC) is a global health problem that frequently presents at advanced stages, is predisposed to recurrence, readily develops resistance to platinum-based drugs, and has a low survival rate. Predictive, preventive, and personalized medicine (PPPM/3PM) offers an integrated solution with the use of genetic, proteomic, and metabolic biomarkers to identify high-risk individuals for early detection. Metabolic reprogramming is one of the key strategies employed by tumor cells to adapt to the microenvironment and support unlimited proliferation. Pyruvate kinases M1 and M2 (PKM1/2) are encoded by the gene, a pivotal enzyme in the last step of the glycolytic pathway, which is at the crossroads of aerobic oxidation and the Warburg effect to serve as a potential regulator of glucose metabolism and influence cellular energy production and metabolic reprogramming. Commonly, the ratio of PKM1-to-PKM2 is changed in tumors compared to normal controls, and PKM2 is highly expressed in OC to induce a high glycolysis rate and participate in the malignant invasion and metastatic characteristics of cancer cells with epithelial/mesenchymal transition (EMT). PKM2 inhibitors suppress the migration and growth of OC cells by interfering with the Warburg effect. Proteoforms are the final structural and functional forms of a gene/protein, and the canonical protein PKM contains all proteoforms encoded by the same gene. The complexity of PKM can be elucidated by proteoformics. The OC-specific PKM proteoform might represent a specific target for therapeutic interventions against OC. In the framework of PPPM/3PM, the OC-specific PKM proteoform might be the early warning and prognosis biomarker. It is important to clarify the molecular mechanisms of PKM proteoforms in cancer metabolism. This review analyzes the expression, function, and molecular mechanisms of PKM proteoforms in OC, which help identify specific biomarkers for OC.
卵巢癌（OC）是一个全球性的健康问题，该病常常在晚期出现，易于复发，容易对铂类药物产生耐药性，且生存率较低。预测性、预防性和个性化医学（PPPM/3PM）提供了一种综合解决方案，即利用遗传、蛋白质组学和代谢生物标志物来识别高危个体以便早期检测。代谢重编程是肿瘤细胞用来适应微环境并支持无限增殖的关键策略之一。丙酮酸激酶M1和M2（PKM1/2）由 基因编码，它是糖酵解途径最后一步中的关键酶，处于有氧氧化和瓦伯格效应的交叉点，可作为葡萄糖代谢的潜在调节因子，并影响细胞能量产生和代谢重编程。通常，与正常对照相比，肿瘤中PKM1与PKM2的比例会发生变化，并且PKM2在OC中高表达，以诱导高糖酵解率，并参与具有上皮/间质转化（EMT）的癌细胞的恶性侵袭和转移特性。PKM2抑制剂通过干扰瓦伯格效应来抑制OC细胞的迁移和生长。蛋白质异构体是基因/蛋白质的最终结构和功能形式，经典蛋白质PKM包含由同一 基因编码的所有蛋白质异构体。PKM的复杂性可以通过蛋白质异构体组学来阐明。OC特异性PKM蛋白质异构体可能代表针对OC的治疗干预的特定靶点。在PPPM/3PM框架内，OC特异性PKM蛋白质异构体可能是早期预警和预后生物标志物。阐明PKM蛋白质异构体在癌症代谢中的分子机制很重要。本综述分析了PKM蛋白质异构体在OC中的表达、功能和分子机制，这有助于识别OC的特异性生物标志物。
