Pan-Cancer Analysis of PGAM1 and Its Experimental Validation in Uveal Melanoma Progression

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.

Multi-omic profiling of breast tumor microenvironment uncovers a role of mitochondrial calcium gatekeepers

“…Our findings revealed a strong positive correlation between the expression of MiCU1/2 and macrophages, suggesting a potential role of MiCU1/2 in regulating the differentiation and activation of immune cells within TIME. More than half of the cellular constituents within tumor tissue are comprised of macrophages 30 . Initially thought to eliminate tumor cells, it has been discovered through research that macrophages can coexist with tumor cells and may even facilitate tumor advancement and metastasis 31 .…”