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.

Identification and validation of a novel cellular senescence-related lncRNA prognostic signature for predicting immunotherapy response in stomach adenocarcinoma

“…AC007405.2, AL033527.2, and AC083902.1 were identified for the first time. AL136115.1, AL355574.1, and REPIN1-AS1 were reported as favorable underlying factors for STAD patients ( Chen et al, 2021 ; Zhang et al, 2021 ; Luo et al, 2022 ), while AL391152.1 ( Liu et al, 2020 ), AC005165.1 ( Wang et al, 2022 ), AC104695.3 ( Zhang et al, 2021 ), and AC129507.1 ( Zha et al, 2021 ) were risk lncRNAs for STAD patients, which is consistent with our results. ADAMTS9-AS1 can inhibit apoptosis and autophagy through the PI3K/AKT/mTOR signaling pathway and promote bladder cancer progression ( Yang et al, 2021 ) while inhibiting colon cancer cell progression through the Wnt/β-catenin signaling pathway ( Li et al, 2020 ).…”

Screening and validation of platelet activation-related lncRNAs as potential biomarkers for prognosis and immunotherapy in gastric cancer patients

“…Xu et al established an m6A-related lncRNAs model and confirmed the model’s important effect in predicting the prognosis of patients with lung adenocarcinoma (LUAD), providing guidance for the immunotherapy of patients with LUAD ( Xu et al, 2021 ). Furthermore, a recent study on the effect of autophagy on GC constructed a prognostic model containing five autophagy-related lncRNAs, indicating the key role of autophagy-related lncRNAs in GC and suggesting that these lncRNAs may be effective targets for immunotherapy point ( Chen et al, 2021a ). In addition, models of ferroptosis-related lncRNAs, necroptosis-related lncRNAs, and pyroptosis-related lncRNAs have also been established, providing new targets for the study of the molecular mechanism, and the immunotherapy of malignant tumors ( Song et al, 2021 ; Xiao et al, 2021 ; Zhao et al, 2021 ).…”

“…Seven PLT-related lncRNAs (AL355574.1, LINC01697, AC002401.4, AC129507.1, AL513123.1, LINC01094, AL356417.2) were identified by LASSO regression analysis and used to construct the prognostic model for predicting OS in GC patients. AL355574.1 was identified as a protective lncRNA associated with autophagy in GC, which can be used as a promising therapeutic target for immunotherapy in GC patients ( Chen et al, 2021a ). Zhang et al pointed out that LINC01697, as a ceRNA, could be used as a biomarker for the prognosis of GC patients and was up-regulated in GC cells, while its knockdown can inhibit the proliferation of GC cells ( Zhang et al, 2021 ).…”

Establishment and Analysis of a Prognostic Model of Autophagy-Related lncRNAs in ESCA

“…Chen et al reported that autophagy-related lncRNA prognostic markers, such as AL355574.1, are associated with the immune microenvironment and survival outcomes in patients with gastric cancers [19]. Increasing studies have found that lncRNAs affect the malignant progression of tumors by regulating autophagy [20][21][22][23][24]; however, the specific mechanism by which this regulation occurs remains unclear.…”