A Novel m6A-Related LncRNA Signature for Predicting Prognosis, Chemotherapy and Immunotherapy Response in Patients with Lung Adenocarcinoma

Abstract

N6-methyladenosine (m6A) and long non-coding RNA (lncRNA) have been associated with cancer prognosis and the effect of immunotherapy. However, the roles of m6A-related lncRNAs in the prognosis and immunotherapy in lung adenocarcinoma (LUAD) patients remain unclear. We evaluated the m6A modification patterns of 695 samples based on m6A regulators, and prognostic m6A-related lncRNAs were identified via a weighted gene co-expression network analysis. Twelve abnormal m6A regulators and nine prognostic lncRNAs were identified. The tumor microenvironment cell-infiltrating characteristics of three m6A-related lncRNA clusters were highly consistent with the three immune phenotypes of tumors, including immune-excluded, immune-inflamed and immune-desert phenotypes. The lncRNA score system was established, and high lncRNA score patients were associated with better overall survival. The lncRNA score was correlated with the expression of the immune checkpoints. Two immunotherapy cohorts supported that the high lncRNA score enhanced the response to anti-PD-1/L1 immunotherapy and was remarkably correlated with the inflamed immune phenotype, showing significant therapeutic advantages and clinical benefits. Furthermore, the patients with high lncRNA scores were more sensitive to erlotinib and axitinib. The lncRNA score was associated with the expression of miRNA and the regulation of post-transcription. We constructed an applied lncRNA score-system to identify eligible LUAD patients for immunotherapy and predict the sensitivity to chemotherapeutic drugs.

Development of m6A/m5C/m1A regulated lncRNA signature for prognostic prediction, personalized immune intervention and drug selection in LUAD

“…Based on the screening criteria we set, we found eight studies, 75 , 76 , 77 , 78 , 79 , 80 , 81 , 82 but one of them was removed because it did not contain coefficient information. Finally, seven studies came into our view 75 , 77 , 78 , 79 , 80 , 81 , 82 (Table 4 ).…”

Overview of the interplay between m6A methylation modification and non-coding RNA and their impact on tumor cells

“…Upregulation of nine m6A-related lncRNAs (e.g., linc01117, linc00592, tmpo.as1) in lung adenocarcinoma is associated with lower overall survival. The risk score generated from these lncRNAs can serve as an independent prognostic marker for lung adenocarcinoma, with patients exhibiting higher scores demonstrating increased sensitivity to PD-1/L1 immunotherapy and targeted therapy ( 125 ). Current research suggests that risk scoring models based on m6A-related lncRNAs can serve as prognostic indicators for malignant tumors in various cancers, including gastric cancer, bladder cancer, and breast cancer.…”

An anoikis-related lncRNA signature is a useful tool for predicting the prognosis of patients with lung adenocarcinoma

“…Through their multifaceted functions [ 25 ], lncRNAs can regulate nucleosome assembly and functions, control chromatin activities, directly bind to target RNAs to modulate translation or stability [ 26 ], and interfere with signaling pathways, thereby participating in gene regulation [ 27 ]. As crucial regulatory molecules, lncRNAs play a pivotal role in various biological processes, including apoptosis, cell migration, cell proliferation, and metabolic regulation, operating through diverse pathways [ 28 ], particularly during tumorigenesis [ 29 ]. Consequently, dysregulated lncRNAs hold potential as prognostic biomarkers for tumors [ 30 ].…”