LHPP is associated with favorable survival across diverse cancers with tumor suppressor properties in stomach adenocarcinoma: a pan-cancer analysis

Abstract Background The down-regulation of LHPP has been reported as a tumor suppressor gene in several malignancies. This study aims to explore the potential roles of LHPP across 33 types of tumors. Methods The TCGA database was mainly used to investigate the correlation of LHPP expression pattern with clinical prognosis and other function related gene sets. Additionally, immunohistochemistry and western blot assay were used to detect the expression level of LHPP in tissue samples for stomach adenocarcinoma (STAD) patients. We next established STAD cell lines with exogenous silencing/ overexpression of LHPP. qRT-PCR, western blot assay, CCK-8 assay and colony formation assays were performed for cell function identifications. Results LHPP was widely down-regulated in tumor tissues compared with normal tissues in pan-cancer across 13 cancer types. The expression level of LHPP was associated with favorable survival across diverse cancers. Moreover, we observed that LHPP expression was significantly correlated with immune infiltration, tumor mutation burden (TMB), microsatellite instability (MSI), mismatch repair genes (MMRs), and DNA methyltransferases in many tumors. Validation in clinical tissue samples confirmed LHPP was down-regulated in STAD. Functional experiments demonstrated that LHPP suppressed cell proliferation of STAD via down-regulating p‑PI3K/p‑AKT expression levels. Conclusion Our first pan-cancer study provided insight into the role of LHPP in tumorigenesis. Besides, LHPP may acts as a tumor suppressor gene in STAD.