已发表论文

肺腺癌中 m6A 相关长链非编码 RNA 预后特征的开发及 FAM83A-AS1 的功能验证

 

Authors Zhang G, Liu C, Wang Y

Received 7 May 2025

Accepted for publication 27 August 2025

Published 30 September 2025 Volume 2025:18 Pages 1107—1123

DOI https://doi.org/10.2147/OTT.S538953

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Dr Lukas Hawinkels

Guojun Zhang,1 Cheng Liu,2 Yukun Wang3,4 

1Department of Clinical Nutrition, Hospital of Southern University of Science and Technology, Shenzhen, People’s Republic of China; 2School of Medicine, Southern University of Science and Technology, Shenzhen, People’s Republic of China; 3Department of Pharmacy, Hospital of Southern University of Science and Technology, Shenzhen, People’s Republic of China; 4Department of Pharmacology, School of Medicine, Southern University of Science and Technology, Shenzhen, People’s Republic of China

Correspondence: Guojun Zhang, Email a958532646@126.com

Introduction: This work aimed to identify m6A-related long non-coding RNAs (lncRNAs) associated with lung adenocarcinoma (LUAD) and evaluate their prognostic value and to examine the oncogenic actions of FAM83A-AS1 in LUAD.
Methods: The m6A-related lncRNAs in LUAD were identified by correlating lncRNA expression profiles with known m6A regulators using TCGA RNA-seq data. Prognostic lncRNAs were selected through univariate and multivariate Cox regression analyses and integrated into a risk model termed m6ARLSig. The model’s predictive performance was assessed using Kaplan-Meier survival analysis, ROC curves, and principal component analysis. Immune infiltration and therapeutic responses were evaluated using CIBERSORT and drug sensitivity prediction. In vitro assays were conducted in A549 and A549/DDP cell lines to assess the oncogenic and drug resistance roles of FAM83A-AS1.
Results: We screened a set of m6A-related genes and identified a subset of m6A related-lncRNAs from TCGA through correlation analysis. Eight m6A-related lncRNAs were significantly associated with patient outcomes. AL606489.1 and COLCA1 functioned as independent adverse prognostic biomarkers, whereas six long non-coding RNAs served as independent favorable predictors of overall survival (OS). Eight lncRNAs were employed to develop a prognostic m6A-associated lncRNA signature (m6ARLSig). Based on personalized m6ARLSig levels, we computed a risk score for each individual and stratified the cohort into low-risk and high-risk categories. Survival analysis revealed a marked divergence in overall survival between the low- and high-risk cohorts, thereby substantiating the m6ARLSig’s prognostic utility. In multivariate modeling, the m6ARLSig remained an independent predictor of prognosis. A nomogram incorporating m6ARLSig and clinicopathological parameters was constructed, providing a clinically adaptable tool for survival probability estimation. FAM83A-AS1 knockdown repressed A549 proliferation, invasion, migration, EMT, but increased apoptosis. Additionally, FAM83A-AS silence also attenuated cisplatin resistance of A549/DDP cells.
Conclusion: Collectively, we identified a novel m6ARLSig with prognostic value in LUAD. The m6ARLSig showed associations with clinicopathological parameters, immune cell infiltration, and therapeutic responses. FAM831-AS1 may play oncogenic role in LUAD.

Keywords: m6A-related lcnRNAs, lung adenocarcinoma, prognostic signature, tumor microenvironment, FAM83A-AS1, cisplatin resistance