A Novel Autophagy-Related lncRNA Prognostic Signature Associated with Immune Microenvironment and Survival Outcomes of Gastric Cancer Patients.

Abstract

PURPOSE:

Autophagy plays a crucial role in the initiation and progression of gastric cancer (GC). However, the role of autophagy-related lncRNAs in GC remains unknown. This study aimed to investigate the prognostic value of the autophagy-related lncRNA signature and its role in the tumor immune microenvironment (TIME) of GC.

METHODS:

RNA-sequencing (RNA-seq) and clinical data of GC patients were extracted from The Cancer Genome Atlas (TCGA) database. Univariate and multivariate Cox regression analyses were performed to identify the autophagy-related lncRNA prognostic signature which was validated in the test set and entire set. The survival and predictive performance were analyzed based on the Kaplan-Meier and ROC curves. Furthermore, the CIBERSORT algorithm was applied to explore the relationship between this signature and the immune cell infiltration. To elucidate the potential functions of autophagy-related lncRNAs in GC, we constructed the lncRNA-mRNA co-expression network and performed enrichment analysis. Principal component analysis (PCA) and Gene Set Enrichment Analysis (GSEA) were further performed to compare the different statuses between the high-risk and low-risk groups.

RESULTS:

We identified 5 autophagy-related lncRNAs (AL355574.1, AC010768.2, AP000695.2, AC087286.2, and HAGLR) to construct a prognostic signature. This signature could be an independent prognostic indicator for GC patients and had a higher prediction efficiency than other clinicopathological parameters. Furthermore, patients in the high-risk score group had a stronger immunosuppressive microenvironment than the low-risk group. The enrichment analysis for mRNAs co-expressed with these lncRNAs indicated that autophagy-related signaling pathways were remarkably enriched. PCA and GSEA further revealed different autophagy and immune statuses in the high- and low-risk groups.

CONCLUSION:

The 5 autophagy-related lncRNA signature has significant clinical implications in prognosis prediction of GC. Meanwhile, our study elucidates the critical role of the autophagy-related lncRNA signature in the TIME of GC.

• Authors: Di Chen, Mengmeng Wang, Yushuang Xu, Xin Jiang, Lina Xiong, Li Zhang, Honglu Yu, Zhifan Xiong
• Journal: International journal of general medicine (Int J Gen Med) Vol. 14 Pg. 6935-6950 ( 2021) ISSN: 1178-7074 [Print] New Zealand
• PMID: 34703297 (Publication Type: Journal Article)
• Copyright: © 2021 Chen et al.