IntroductionPTGES3, also known as p23, is a molecule chaperone of Hsp90 that is involved in the pathogenesis of malignant tumors. Increasing studies have shown that PTGES3 plays a nonnegligible role in tumor development. However, analysis of PTGES3 in pan-cancer has not been performed yet.MethodsWe explored the role of PTGES3 in 33 types of tumors and depicted the potentialimmune-related pathways among them. Using multiple databases includingTCGA, LinkedOmics, GDSC, and TIMER, we made a comprehensive analysis to explore whether there was an interaction between PTGES3 and prognosis, DNA methylation, copy number variation (CNV), tumor mutational burden (TMB), microsatellite instability (MSI), and tumor immune microenvironment (TME).ResultsOur study revealed that PTGES3 expression level was upregulated in most cancers. PTGES3 was also associated with a positive or negative prognosis in a variety of cancers, which was mainly associated with DNA methylation, CNV, MSI, TMB, andmismatch repair-related genes. High PTGES3 expression was related to the infiltration of Th2 subsets of CD4+ T cells and immune checkpoint-related genes in most cancers, especially in hepatocellular carcinoma (HCC). Enrichment analysis demonstrated that PTGES3 was involved in cellular processes including DNA replication and spliceosome. The relationship between PTGES3 expression and HCC progression was verified at the protein level through immune histochemical analysis.ConclusionsOur research demonstrated theprognostic predictive value of PTGES3 in a wide range of cancers, which was alsoassociated with the process of tumor immune infiltration. As a result, it suggestedthat PTGES3 was a valuable prognostic biomarker in HCC treatment.