Construction of an autophagy-related eleven long noncoding RNA signature to predict the outcomes, immune cell infiltration, and immunotherapy response in patients with gastric cancer.

Abstract

Long noncoding RNAs (LncRNAs) may be involved in the occurrence, development, and drug resistance of gastric cancer (GC) by regulating autophagy. This study aims to establish an autophagy-related LncRNA (ARL) signature (ARLSig) and explore its immunogenomic implications in patients with GC. The RNA sequencing and clinical data of patients with GC from The Cancer Genome Atlas database, and autophagy genes from the Human Autophagy Database were extracted. The co-expression and Cox regression analyses were performed to establish a prognostic ARLSig. Further, the differences in clinicopathology, immune microenvironment, immune function, and response to immunotherapy between the risk groups were explored by several algorithms. A prognostic risk model consisting of 11 ARLs was constructed. The clinical correlation analysis between the ARLSig and clinicopathological factors indicated that the ARLSig was correlated with the comprehensive, T, and N stages (all P<0.05). Further, a nomogram including the ARLSig and clinical factors suggested it had a powerful predictive value for survival, with a higher prediction efficiency for 1-, 3-, and 5-year survival than other clinicopathological factors. Finally, the immune-related analysis between the two risk groups showed that the high-risk group had significantly higher infiltration proportions of natural killer cells resting, monocytes, M2 macrophages, and dendritic cells resting, as well as higher expression of 25 immune checkpoint genes. In addition, the immunotherapy response prediction by the tracking of indels by decomposition algorithm showed the low-risk group was more sensitive to immune checkpoint inhibitor therapy. The ARLSig consisting of 11 ARLs in GC showed highly efficient predictive value for survival of patients with GC and might provide novel targets for their individualized immunotherapy.