Abstract
LY6H, a member of the lymphocyte antigen-6(LY6) gene family, is located on human chromosomes 6, 8, 11 and 19. This superfamily is characterized by the presence of LU domains. It has demonstrated its emerging significance in various cancers including adenocarcinoma, bladder cancer, ovarian cancer and skin cancer. However, comprehensive pan-cancer analyses have not been conducted to investigate its role in diagnosis, prognosis and immunological prediction. By conducting comprehensive analysis of patient data obtained from publicly available databases, including The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), University of Alabama at Birmingham (UALCAN), The Comparative Toxicological Genomics Database (CTD), cBioportal, cancerSEA, and UCSC, we systematically investigated the differential expression of LY6H in 33 different types of human tumors. Additionally, we thoroughly analyzed the diagnostic, prognostic, and immunoinfiltration value of LY6H. Simultaneously, we examined the correlation between LY6H and tumor stemness, methylation patterns, drug sensitivity, gene alterations as well as single cell functions. Furthermore, protein-protein interaction networks and gene-gene interaction networks for LY6H were constructed. Moreover, we also explored the network relationship between LY6H and chemical compounds or genes. The results revealed that LY6H exhibited high expression levels in most cancers which were further validated through Reverse Transcription-Polymerase Chain Reaction (RT-PCR) and Immunohistochemistry (IHC) analysis using Hepatocellular carcinoma (HCC) samples. Moreover, LY6H displayed early diagnostic potential in 12 tumors while also showing positive or negative correlations with prognosis across different tumor types. Additionally, it was found that LY6H played a pivotal role in regulating immune-infiltrating cells across multiple cancers whereas the correlation between LY6H expression and immune-related genes varied depending on their specific types. Furthermore, the expression of LY6H was significantly associated with DNA methylation patterns in 21 cancers. Therefore, LY6H could serve as an adjunctive biomarker for early tumor detection as well as a prognostic indicator for diverse malignancies.