Abstract
BACKGROUND: LRRC59 is a leucine-rich repeats-containing protein located in the endoplasmic reticulum (ER), it serves as a prognostic marker in several cancers. However, there has been no systematic analysis of its role in the tumor immune microenvironment, nor its predictive value of prognosis and immunotherapy response in different cancers. METHODS: A comprehensive pan-cancer analysis of LRRC59 was conducted from various databases to elucidate the associations between its expression and the prognosis of cancer, genetic alterations, tumor metabolism, and tumor immunity. Additionally, further functional assays were performed in hepatocellular carcinoma (HCC) to study its biological role in regulating cell proliferation, migration, apoptosis, cell cycle arrest, and sensitivity to immunotherapy. RESULTS: The pan-cancer analysis reveals a significant upregulation of LRRC59 in pan-cancer, and its overexpression is correlated with unfavorable prognosis in cancer patients. LRRC59 is negatively correlated with immune cell infiltration, tumor purity estimation, and immune checkpoint genes. Finally, the validation in HCC demonstrates LRRC59 is significantly overexpressed in cancer tissue and cell lines, and its knockdown inhibits cell proliferation and migration, promotes cell apoptosis, induces cell cycle arrest, and enhances the sensitivity to immunotherapy in HCC cells. CONCLUSIONS: LRRC59 emerges as a novel potential prognostic biomarker across malignancies, offering promise for anti-cancer drugs and immunotherapy.