A Pan-Cancer Analysis Reveals the Prognostic Significance and Oncogenic Role of LncRNA TUG1

Abstract

Background: LncRNA taurine up-regulated gene1 (TUG1) is a valuable lncRNA that is abnormally expressed in a number of tumor types. However, investigations into its expression, prognostic implications, and associations with the tumor microenvironment and immunity remain limited. In this study, we evaluated the prognostic value and oncogenic potential of TUG1, and its relationship with pathological parameters, immune infiltration, and cancer drug sensitivity. Methods: Using data from The Cancer Genome Atlas (TCGA), Sangerbox, and the Cancer Cell Line Encyclopedia (CCLE), we analyzed TUG1 expression. Kaplan-Meier and Cox regression analyses were employed to evaluate the prognostic significance of TUG1 in pan-cancer. The association between TUG1 expression and methylation, tumor mutational burden (TMB), microsatellite instability (MSI), immune infiltration, immune checkpoints, and drug sensitivity was examined. Results: In adrenocortical carcinoma (ACC) and liver hepatocellular carcinoma (LIHC), TUG1 overexpression was related to poorer overall survival (OS). In glioblastoma multiforme (GBM), lower grade glioma (LGG) and pheochromocytoma and paraganglioma (PCPG), increased TUG1 was related to better OS. In ACC and LGG, TUG1 may be an independent prognostic factor. Gene set enrichment analysis (GSEA) highlights the involvement of TUG1 in various tumorigenic and signaling pathways. Additionally, TUG1 was associated with TMB in 12 tumor types and with MSI in 11 cancer types. TUG1 expression was positively correlated with Chelerythrine, Nelarabine, Methylprednisol, AZD-9496, and ZM-336372, while it negatively correlated with CG-806, BPTES, Vincristine, AZD-4547, CFI-400945, XR-5944, and Danusertib. Conclusions: Our findings revealed dysregulated TUG1 expression in the human pan-cancer dataset. Drug sensitivity analysis suggested a potential association between TUG1 and drug resistance of specific drugs. Moreover, TUG1 expression was correlated with immune checkpoint genes, immune cell infiltration, and the tumor microenvironment across various cancers, underscoring its potential as a promising target for tumor prognosis and treatment. Our findings highlight the fundamental impact of TUG1 across multiple cancer types, offering insights that could pave the way for novel therapeutic strategies in cancer patients.