Multi-Omics Pan-Cancer Profiling of HSD17B10 Unveils Its Prognostic Potential, Metabolic Regulation, and Immune Microenvironment Interactions

This study systematically analyzed the expression and clinical significance of Hydroxysteroid 17-beta dehydrogenase type 10 (<i>HSD17B10</i>) in 33 cancers by integrating TCGA, GTEx, and other multi-omics databases. <i>HSD17B10</i> was highly expressed in 14 cancers, like GBM and LGG, but low in 5, such as KIRC. Its expression correlated closely with overall survival (OS) and disease-free survival (DFS). In GBM-LGG, LGG, and other cancers, high <i>HSD17B10</i> expression was linked to lower survival rates, indicating that it could be an independent prognostic marker. <i>HSD17B10</i> also had a two-way relationship with the tumor's immune microenvironment. In cancers such as GBM-LGG, high expression correlated positively with immune/stromal scores. However, in most cancers like LUAD, it was negatively associated with B- and T-cell infiltration. Epigenetic analysis showed that low methylation in the <i>HSD17B10</i> promoter region might drive its high expression in tumors such as SARC, and specific methylation sites (e.g., CG26323797) were significantly related to patient survival. Functional enrichment analysis revealed that <i>HSD17B10</i> participated in tumor progression by regulating oxidative phosphorylation, mitochondrial metabolism, and RNA methylation. Single-cell and spatial transcriptome data further demonstrated that <i>HSD17B10</i> had a cell-type-specific expression pattern in colorectal cancer. This study provides a theoretical basis for <i>HSD17B10</i> as a pan-cancer prognostic marker and therapeutic target.