Pan-cancer analysis of the oncogenic effects of G-protein-coupled receptor kinase-interacting protein-1 and validation on liver hepatocellular carcinoma

Background.Despite G-protein-coupled receptor kinase-interacting protein-1 (GIT1) being recognized as a new promoter gene in some types of cancer, its effect on human pan-cancers and liver hepatocellular carcinoma (LIHC) remains unclear. Objectives.To elucidate the molecular mechanisms of GIT1 in pan-cancer and LIHC. Materials and methods.Various bioinformatics approaches were utilized to elucidate the oncogenic effects of GIT1 on human pan-cancers.Results.The GIT1 was aberrantly expressed in pan-cancers and associated with the clinical stage.Moreover, the upregulation of GIT1 expression was indicative of poor overall survival (OS) in patients with LIHC, skin cutaneous melanoma (SKCM) and uterine corpus endometrial carcinoma (UCEC), as well as of poor disease-free survival (DFS) in patients with LIHC and UCEC.Furthermore, GIT1 levels were correlated with cancer-associated fibroblasts (CAFs) in adrenocortical carcinoma (ACC), cervical squamous cell carcinoma (CESC) and LIHC.The analysis of single-cell sequencing data revealed an association of GIT1 levels with apoptosis, cell cycle and DNA damage.In addition, multivariate Cox analysis indicated that high GIT1 levels were an independent risk factor for shorter OS in patients with LIHC.Finally, the gene set enrichment analysis revealed INFLAMMATORY_RESPONSE pathway and IL2_STAT5_SIGNALING to be the most enriched in LIHC. Conclusions.Our data demonstrate the oncogenic effects of GIT1 on various cancers.We believe that GIT1 can serve as a biomarker for LIHC.