ISSN: 1837-9664Journal of Cancer
Global reach, higher impact
J Cancer 2024; 15(7):2074-2094. doi:10.7150/jca.93398 This issue Cite
Research Paper
Pan-Cancer Analysis of PGAM1 and Its Experimental Validation in Uveal Melanoma Progression
1. 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.
2. Department of Pharmacy, Henan Provincial People's Hospital, Zhengzhou University People's Hospital, Henan University People's Hospital, Zhengzhou 450003, Henan, China.
3. Microbiome Laboratory, Henan Provincial People's Hospital, Zhengzhou University People's Hospital, Henan University People's Hospital, Zhengzhou 450003, Henan, China.
4. Institute of Chemistry Henan Academy of Sciences, No. 56 Hongzhuan Road, Jinshui District, Zhengzhou 450002, China.
5. Shandong Academy of Chinese Medicine, Jinan 250014, China.
6. Department of Pharmacy, Jinan Vocational College of Nursing, Jinan 250102, China.
Abstract
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.
Keywords: PGAM1, UVM, Immune infiltration, EMT, Apoptosis
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