PGLS as an immune and prognostic biomarker: from pan-cancer analysis to validation

6-phosphogluconolactonase (PGLS) is a metabolic enzyme of the pentose phosphate pathway that has been linked to tumorigenesis in several cancers. However, its role in pan-cancer remains unclear. This study reveals the expression profile and prognostic analysis of PGLS in different cancers by pan-cancer analysis. We utilized mRNA-seq data from TCGA and GTEx databases to analyze PGLS expression in different tumors. PGLS expression was significantly higher in almost all types of human cancer tissues compared to corresponding normal tissues. High PGLS expression was linked to poor prognosis. PGLS expression was significantly associated with immune regulatory genes, immune cell infiltration, tumor heterogeneity, tumor stemness, and involved in the regulation of anticancer drug sensitivity. Knockdown of PGLS resulted in slowed growth and diminished migratory and invasive capacity of Huh7 and A498 cells. Additionally, PGLS knockdown led to an increase in M1 macrophages, CD8⁺ T cells, and CD4⁺ T cells, while reducing the proportion of M2 macrophages and Tregs in tumor tissue. PGLS could serve as a potential therapeutic target and a reliable predictor of both prognostic factors and treatment sensitivity across various types of tumors. Further studies are warranted to explore its clinical application in cancer treatment.