PKM2 modulates chemotherapy sensitivity by regulating autophagy and predicts the prognosis and immunity in pancancer

被引：0
作者：
Haosheng Zheng [1 ]
Jian Tan [2 ]
Fei Qin [1 ]
Yuzhen Zheng [2 ]
Xingping Yang [1 ]
Zui Liu [2 ]
Weijie Cai [1 ]
Xianyu Qin [2 ]
Hongying Liao [1 ]
机构：
[1] Department of Thoracic Surgery, Thoracic Cancer Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangdong, Guangzhou
[2] Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou
来源：
Scientific Reports | / 15卷 / 1期
关键词：
Chemotherapy; Immune cell infiltration; Immunotherapy; Pan-cancer; PKM2; prognosis; Tumor microenvironment;
D O I：
10.1038/s41598-025-96562-x
中图分类号：
学科分类号：
摘要：
One of the main characteristics of tumor metabolite reprogramming is enhanced glycolysis, and Pyruvate Kinase M2(PKM2) is a crucial enzyme that limits the pace of glycometabolism. Although PKM2 has been proven to affect the development of some cancers, a pan-cancer analysis of PKM2 has not yet been performed. We analyzed the expression and prognosis of PKM2 in pan-cancer using multiple databases. We performed epigenetic, functional enrichment, immune cell infiltration, immune checkpoint, and drug sensitivity analyses of PKM2. PKM2 was found to be significantly upregulated in most malignancies and associated with a bad prognosis. In some cancers, the PKM2 DNA promoter was hypomethylated. The expression of PKM2 was positively linked with most m6A-methylation-related genes in pan-cancer. The functions of PKM2 were primarily associated with the regulation of the immune system, glycolysis, hypoxia, angiogenesis, and epithelial-mesenchymal transition. PKM2 was favorably associated with neutrophils and cancer-associated fibroblasts in the tumor microenvironment of most cancers. Importantly, PKM2 showed a strikingly high correlation with CD274 (PD-L1), CD276, TGF-β1, VEGFA, and HAVCR2 in most cancers. Finally, using experiments, it was confirmed that silencing PKM2 could increase the sensitivity of esophageal squamous cell carcinoma to cisplatin by regulating autophagy. PKM2 affects autophagy - regulated tumor cell tolerance to chemotherapy, providing future research directions for solving tumor chemotherapy resistance. © The Author(s) 2025.
引用
收藏
相关论文
共 56 条
  • [1] Siegel R.L., Miller K.D., Wagle N.S., Jemal A., Cancer statistics, 2023, CA Cancer J. Clin, 73, pp. 17-48, (2023)
  • [2] Zhang Y., Zhang Z., The history and advances in cancer immunotherapy: Understanding the characteristics of tumor-infiltrating immune cells and their therapeutic implications, Cell. Mol. Immunol, 17, pp. 807-821, (2020)
  • [3] Marcus L., Lemery S.J., Keegan P., Pazdur R., FDA approval summary: Pembrolizumab for the treatment of microsatellite Instability-High solid tumors, Clin. Cancer Res, 25, pp. 3753-3758, (2019)
  • [4] Cooper L.A., Et al., PanCancer insights from the cancer genome atlas: The pathologist’s perspective, J. Pathol, 244, pp. 512-524, (2018)
  • [5] Pavlova N.N., Zhu J., Thompson C.B., The hallmarks of cancer metabolism: Still emerging, Cell. Metab, 34, pp. 355-377, (2022)
  • [6] Liberti M.V., Locasale J.W., The Warburg effect: How does it benefit cancer cells??, Trends Biochem. Sci, 41, pp. 211-218, (2016)
  • [7] Dayton T.L., Jacks T., Vander Heiden M.G., PKM2, cancer metabolism, and the road ahead, EMBO Rep, 17, pp. 1721-1730, (2016)
  • [8] Zhu K., Et al., Significant association of PKM2 and NQO1 proteins with poor prognosis in breast cancer, Pathol. Res. Pract, 216, (2020)
  • [9] Zhan C., Shi Y., Lu C., Wang Q., Pyruvate kinase M2 is highly correlated with the differentiation and the prognosis of esophageal squamous cell cancer, Dis. Esophagus, 26, pp. 746-753, (2013)
  • [10] Li T.-E., Et al., PKM2 drives hepatocellular carcinoma progression by inducing immunosuppressive microenvironment, Front. Immunol, 11, (2020)
123456