A novel signature based on autophagy-related lncRNA for prognostic prediction and candidate drugs for lung adenocarcinoma

Zetian Gong; Qifan Li; Jun Li; Jiaheng Xie; Wei Wang

doi:10.21037/tcr-21-1554

A novel signature based on autophagy-related lncRNA for prognostic prediction and candidate drugs for lung adenocarcinoma

Transl Cancer Res. 2022 Jan;11(1):14-28. doi: 10.21037/tcr-21-1554.

Authors

Zetian Gong^#¹, Qifan Li^#², Jun Li^#¹, Jiaheng Xie³, Wei Wang¹

Affiliations

¹ Department of Thoracic Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
² The First Affiliated Hospital of Soochow University, Soochow, China.
³ Department of Burn and Plastic Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.

^# Contributed equally.

Abstract

Background: Autophagy inhibits tumorigenesis by limiting inflammation. Various lncRNAs are associated with tumour biological processes, including lung adenocarcinoma (LUAD), but the role of autophagy-related lncRNAs (ARlncRNAs) in LUAD has not been fully elucidated. Thus, this study aimed to construct a prognostic signature based on ARlncRNAs for LUAD.

Methods: The RNA-seq (FPKM) data and clinical information of LUAD patients were downloaded from The Cancer Genome Atlas (TCGA) database. After differentially expressed lncRNAs in tumour and normal groups were identified, cox regression analyses were performed to construct a prognostic signature which was then assessed through independent prognostic analysis and functional enrichment analysis. Moreover, based on the mRNAs co-expressed with the ARlncRNAs, several potential small molecule drugs were explored in the Connectivity map (Cmap).

Results: A signature consisting of seven ARlncRNAs (FAM83A-AS1, LINC01116, ILF3-DT, EBLN3P, AL161785.1, AC092279.1 and AC026355.2) was constructed to predict overall survival (OS) for LUAD. The signature was identified to be independent by the cox regression analysis and obtained the largest area under the curve (AUC =0.721) in the receiver operating characteristic (ROC). Six small molecule drugs (MS-275, methotrexate, desipramine, benzbromarone, rifampicin and doxazosin) were selected from Cmap.

Conclusions: A novel ARlncRNA signature for LUAD prognostic prediction was constructed, which had better efficacy than the TNM stage and used to propose potential therapeutic regimens for LUAD patients.

Keywords: FAM83A−AS1; LINC01116; Lung adenocarcinoma (LUAD); autophagy; prognostic signature.