Identification of the three subtypes and the prognostic characteristics of stomach adenocarcinoma: analysis of the hypoxia-related long non-coding RNAs.

Abstract

Stomach adenocarcinoma (STAD) is one of the most commonly diagnosed cancers. This study analyzed the subtypes and characteristics of STAD subtypes by analyzing hypoxia pathway-related lncRNAs. Potential hub lncRNAs were found and a prognostic model was constructed. Expression profiling data and clinical information of STAD were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). Metabolic pathway scores were calculated using single-sample gene set enrichment analysis (ssGSEA) method. Tumor immune microenvironment scores of the samples were assessed by ESTIMATE, MCP-counter, and ssGSEA. Functional analysis of lncRNAs, construction of risk models, and drug sensitivity analysis were performed. Pathway analysis revealed that the hypoxia pathway was a prognostic risk factor. Molecular subtypes were developed based on the hypoxia score-related lncRNAs. Three molecular subtypes (C1, C2, and C3) for gastric STAD were determined. The worst prognosis was in the C2, which was also characterized by the maximum hypoxia pathway-related scores and the maximum immune score. A majority of the immune checkpoints and chemokines were high-expressed in the C2 subtype. Mutations in the C2 subtype were significantly lower than the C1 and C3 subtypes. The subtypes differed in terms of functional and metabolic pathways. Eight hub indicator lncRNAs (MSC-AS1, AC037198.1, LINC00968, AL139393.3, LINC02544, BOLA3-AS1, MIR1915HG, and AC107021.2) capable of predicting patient prognosis were identified. Three hypoxia lncRNA-related molecular subtypes characterized by different prognostic and immune conditions were identified. The results maybe can provide a theoretical basis to improve the clinical diagnosis and treatment of STAD.