Niu Weihong, Yang Yan, Teng Yuetai, Zhang Na, Li Xu, Qin Yinhui
Department of Pathology, Henan Key Laboratory for Digital Pathology Medicine, Henan Provincial People's Hospital, Zhengzhou University People's Hospital, Henan University People's Hospital, Zhengzhou 450003, Henan, China.
Microbiome Laboratory, Henan Provincial People's Hospital, Zhengzhou University People's Hospital, Henan University People's Hospital, Zhengzhou 450003, Henan, China.
J Cancer. 2024 Feb 17;15(7):2074-2094. doi: 10.7150/jca.93398. eCollection 2024.
Phosphoglycerate mutase 1 (PGAM1) is a key enzyme regulating cancer glycolysis. However, the expression and function of PGAM1 in uveal melanoma (UVM) are unknown and systematic analysis is lacking. This study performed a comprehensive analysis of PGAM1 expression across 33 cancer types in multiple public databases. Results demonstrated PGAM1 is aberrantly overexpressed in most tumors compared to normal tissues, and this overexpression is associated with poor prognosis, advanced tumor staging, and aggressive clinical phenotypes in multiple cancers including UVM, lung, breast and bladder carcinomas. In addition, PGAM1 expression positively correlated with infiltration levels of tumor-promoting immune cells including macrophages, NK cells, myeloid dendritic cells, etc. Further experiments showed that PGAM1 was overexpressed in UVM cell lines and tissues, and it was positively associated with a poor prognosis of UVM patients. And knockdown of PGAM1 inhibited migration/invasion and induced apoptosis in UVM cells, followed by decreased levels of PD-L1, Snail, and BCl-2 and increased levels of E-cadherin. Additionally, the correlation analysis and molecular docking results suggest that PGAM1 could interact with PD-L1, Snail and BCl-2. Thus, PGAM1 may promote UVM pathogenesis via modulating immune checkpoint signaling, EMT and apoptosis. Collectively, this study reveals PGAM1 as a valuable prognostic biomarker and potential therapeutic target in aggressive cancers including UVM.
磷酸甘油酸变位酶1（PGAM1）是调节癌症糖酵解的关键酶。然而，PGAM1在葡萄膜黑色素瘤（UVM）中的表达和功能尚不清楚，且缺乏系统分析。本研究在多个公共数据库中对33种癌症类型的PGAM1表达进行了全面分析。结果表明，与正常组织相比，PGAM1在大多数肿瘤中异常过表达，且这种过表达与包括UVM、肺癌、乳腺癌和膀胱癌在内的多种癌症的预后不良、肿瘤分期进展和侵袭性临床表型相关。此外，PGAM1表达与包括巨噬细胞、自然杀伤细胞、髓样树突状细胞等促肿瘤免疫细胞的浸润水平呈正相关。进一步实验表明，PGAM1在UVM细胞系和组织中过表达，且与UVM患者的不良预后呈正相关。敲低PGAM1可抑制UVM细胞的迁移/侵袭并诱导其凋亡，随后PD-L1、Snail和Bcl-2水平降低，E-钙黏蛋白水平升高。此外，相关性分析和分子对接结果表明，PGAM1可与PD-L1、Snail和Bcl-2相互作用。因此，PGAM1可能通过调节免疫检查点信号、上皮-间质转化（EMT）和凋亡来促进UVM发病机制。总体而言，本研究揭示PGAM1是包括UVM在内的侵袭性癌症中有价值的预后生物标志物和潜在治疗靶点。
