m6A-related lncRNAs are potential biomarkers for predicting prognoses and immune responses in patients with LUAD

Abstract

Lung adenocarcinoma (LUAD) is the most frequent subtype of lung cancer worldwide. However, the survival rate of LUAD patients remains low. N6-methyladenosine (m 6 A) and long noncoding RNAs (lncRNAs) play vital roles in the prognostic value and the immunotherapeutic response of LUAD. Thus, discerning lncRNAs associated with m 6 A in LUAD patients is critical. In this study, m 6 A-related lncRNAs were analyzed and obtained by coexpression. Univariate, least absolute shrinkage and selection operator (LASSO), and multivariate Cox regression analyses were conducted to construct an m 6 Arelated lncRNA model. Kaplan-Meier analysis, principalcomponent analysis (PCA), functional enrichment annotation, and nomogram were used to analyze the risk model. Finally, the potential immunotherapeutic signatures and drug sensitivity prediction targeting this model were also discussed. The risk model comprising 12 m 6 A-related lncRNAs was identified as an independent predictor of prognoses. By regrouping the patients with this model, we can distinguish between them more effectively in terms of the immunotherapeutic response. Finally, candidate compounds aimed at LUAD subtype differentiation were identified. This risk model based on the m 6 Abased lncRNAs may be promising for the clinical prediction of prognoses and immunotherapeutic responses in LUAD patients.

N6-Methylandenosine-Related lncRNA Signature Is a Novel Biomarkers of Prognosis and Immune Response in Colon Adenocarcinoma Patients

“…Several studies report that m6A-related lncRNAs are associated with tumor development. The establishment of prognostic models with m6A-related lncRNAs had a good performance in predicting tumor prognosis (Tu et al, 2020;Wang H. et al, 2020;Wang W. et al, 2020;Xu et al, 2021). For example, Zewei Tu develops a prognostic model consisting of nine m6A-related lncRNAs in patients with low-grade gliomas (Tu et al, 2020).…”

“…For example, Zewei Tu develops a prognostic model consisting of nine m6A-related lncRNAs in patients with low-grade gliomas (Tu et al, 2020). m6A-related lncRNAs were potential biomarkers for predicting prognosis and immune response in patients with LUAD (Xu et al, 2021). In gastric cancer, the m6A-related lncRNA signature could serve as a novel prognostic factor (Wang H. et al, 2020).…”

“…Both m6A enzymes and lncRNAs are ideal diagnostic and prognostic markers. Accumulating evidence shows that m6Arelated mRNAs and lncRNAs can serve as novel potential targets to predict the prognosis for multiple cancers (Barros-Silva et al, 2020;Li et al, 2020;Meng et al, 2020;Xu et al, 2020Xu et al, , 2021Jin et al, 2021). For instance, METTL14 is a prognosis-associated regulator of m6A RNA methylation in hepatocellular carcinoma (Li et al, 2020).…”

N6-Methyladenosine RNA Modification: An Emerging Immunotherapeutic Approach to Turning Up Cold Tumors

“…Consequently, defining the context-specific role of m 6 A RNA modification regulators in cancers and their mechanisms will be crucial to direct specific m 6 A RNA modification regulator-based therapeutic interventions in the future. Second, we know that m 6 A RNA modification is found not only in mRNAs but also in non-coding RNAs, and that non-coding RNAs play critical roles in the immune response and immunotherapy in cancers ( Atianand et al, 2017 ; Huang et al, 2020a ); therefore, future studies focused on m 6 A-related non-coding RNAs in cancer will contribute toward the development of more effective and novel cancer immunotherapies ( Chen et al, 2020 ; Xu et al, 2021a ). Third, studies evaluating the use of m 6 A RNA modification as cancer immunotherapy have mainly focused on regulating m 6 A RNA modification regulators through transfection experiments, which are difficult to translate to clinical trials or clinical practice; therefore, m 6 A RNA modification regulator agonists or antagonists should be searched in the future ( Su et al, 2018 ).…”

Construction and Characterization of Long Non-Coding RNA-Associated Networks to Reveal Potential Prognostic Biomarkers in Human Lung Adenocarcinoma

“…ALKBH5 manipulation mediated RMRP suppression, which may be considered as a promising therapeutic target for lung adenocarcinoma (17). Xu et al found a risk model with 12 m6A-related lncRNAs that could be used as an independent predictor of prognoses in LUAD (18). These studies inspired us to comprehensively investigate the lncRNA-related gene crosstalks to identify more diagnosis or prognosis biomarkers and identify more novel molecular therapeutic targets in LUAD.…”