Identification of lncRNAs associated with T cells as potential biomarkers and therapeutic targets in lung adenocarcinoma

Abstract

Lung adenocarcinoma (LUAD) is the most common and deadliest subtype of lung cancer. To select more targeted and effective treatments for individuals, further advances in classifying LUAD are urgently needed. The number, type, and function of T cells in the tumor microenvironment (TME) determine the progression and treatment response of LUAD. Long noncoding RNAs (lncRNAs), may regulate T cell differentiation, development, and activation. Thus, our aim was to identify T cell-related lncRNAs (T cell-Lncs) in LUAD and to investigate whether T cell-Lncs could serve as potential stratifiers and therapeutic targets. Seven T cell-Lncs were identified to further establish the T cell-related lncRNA risk score (TRS) in LUAD. Low TRS individuals were characterized by robust immune status, fewer genomic alterations, and remarkably longer survival than high TRS individuals. The excellent accuracy of TRS in predicting overall survival (OS) was validated in the TCGA-LUAD training cohort and the GEO-LUAD validation cohort. Our data demonstrated the favorable predictive power of the TRS-based nomogram, which had important clinical significance in estimating the survival probability for individuals. In addition, individuals with low TRS could respond better to chemotherapy and immunotherapy than those with high TRS. LINC00525 was identified as a valuable study target, and the ability of LUAD to proliferate or invade was significantly attenuated by downregulation of LINC00525. In conclusion, the TRS established by T cell-Lncs could unambiguously classify LUAD patients, predict their prognosis and guide their management. Moreover, our identified T cell-Lncs could provide potential therapeutic targets for LUAD.