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

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.