Xue Shuaishuai, Luo Ziyi, Mao Yangqi, Liu Siyuan
Department of Neurosurgery, Institute of Brain Diseases, Nanfang Hospital of Southern Medical University, Guangzhou 510515, China.
Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
Gene. 2025 Feb 10;937:149155. doi: 10.1016/j.gene.2024.149155. Epub 2024 Dec 7.
Pyruvate Kinase Muscle Isozyme (PKM), as a member of the pyruvate kinase, is a key enzyme in glycolysis. Numerous tumors have demonstrated its oncogenic properties. There is, however, no pan-carcinogenic analysis for PKM.
A thorough analysis of PKM across various types of cancer was carried out using bioinformatics resources like The National Cancer Institute's Clinical Proteomic Tumor Analysis Consortium (CPTAC) and The Cancer Genome Atlas (TCGA) database. This study involved analyzing the role of PKM in 33 various types of cancers, along with investigating gene expressions, survival rates, clinical importance, genetic changes, immune system presence, and related signaling pathways. Furthermore, we evaluated the effects of PKM knockdown on human colon carcinoma, and glioblastoma cell lines by in vitro experimentation.
In most tumors, PKM expression was markedly increased and was associated with unfavorable overall survival (OS) in certain individuals. In addition, infiltration of macrophages was associated with PKM expression in various tumors. PKM was linked to glycolysis/gluconeogenesis, HIF-1 signaling, carbon metabolism, and NADPH regeneration in a mechanistic manner. Additionally, cell experiments showed that the knockdown of PKM could reduce the proliferation and migration abilities while promoting the apoptosis of Caco-2, and U-87 MG cells.
PKM controls immune cell infiltration, impacts patient outcomes in various types of cancer, and plays an essential role in proliferation and migration in some tumor cells by affecting glycometabolism. The PKM molecule may serve as a potential prognostic biomarker and therapeutic target for human cancers.
丙酮酸激酶肌肉同工酶（PKM）作为丙酮酸激酶家族的一员，是糖酵解中的关键酶。众多肿瘤已证实其具有致癌特性。然而，目前尚无针对PKM的泛癌分析。
利用美国国立癌症研究所的临床蛋白质组肿瘤分析联盟（CPTAC）和癌症基因组图谱（TCGA）数据库等生物信息学资源，对各种癌症类型中的PKM进行了全面分析。本研究分析了PKM在33种不同癌症类型中的作用，同时研究了基因表达、生存率、临床重要性、基因变化、免疫系统存在情况以及相关信号通路。此外，我们通过体外实验评估了PKM敲低对人结肠癌细胞和胶质母细胞瘤细胞系的影响。
在大多数肿瘤中，PKM表达显著增加，且在某些个体中与不良总生存期（OS）相关。此外，巨噬细胞浸润与各种肿瘤中的PKM表达相关。PKM在机制上与糖酵解/糖异生、HIF-1信号传导、碳代谢和NADPH再生有关。此外，细胞实验表明，敲低PKM可降低Caco-2和U-87 MG细胞的增殖和迁移能力，同时促进其凋亡。
PKM控制免疫细胞浸润，影响各种癌症患者的预后，并通过影响糖代谢在某些肿瘤细胞的增殖和迁移中起重要作用。PKM分子可能作为人类癌症的潜在预后生物标志物和治疗靶点。
