AUTHOR=Yang Wei , Ge Fusheng , Lu Shuaibing , Shan Zhiming , Peng Liangqun , Chai Junhui , Liu Hongxing , Li Baodong , Zhang Zhandong , Huang Jinxi , Hua Yawei , Zhang Yonglei TITLE=LncRNA MSC-AS1 Is a Diagnostic Biomarker and Predicts Poor Prognosis in Patients With Gastric Cancer by Integrated Bioinformatics Analysis JOURNAL=Frontiers in Medicine VOLUME=8 YEAR=2021 URL=https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2021.795427 DOI=10.3389/fmed.2021.795427 ISSN=2296-858X ABSTRACT=

Numerous studies have shown that long uncoded RNA (lncRNA) MSC-AS1 may play an important role in the occurrence and development of some types of cancer. However, its role in gastric cancer has rarely been discussed. This study aimed to clarify the association between lncRNA MSC-AS1 and gastric cancer using The Cancer Genome Atlas (TCGA) database. We determined the expression of MSC-AS1 using the Wilcoxon rank sum test; in addition, logistic regression was applied to evaluate the association between MSC-AS1 and clinicopathological characteristics. Also, Kaplan-Meier and Cox regression were used to evaluate the relationship between MSC-AS1 and survival. A nomogram was conducted to predict the impact of MSC-AS1 on prognosis. Moreover, Gene Set enrichment analysis (GSEA) was performed to annotate the biological function of MSC-AS1. Quantitative analysis of immune infiltration was carried out by single-set GSEA (ssGSEA). The MSC-AS1 level was elevated in gastric cancer tissues. An increased MSC-AS1 level was significantly correlated with T stage (odds ratio [OR] = 2.55 for T3 and T4 vs. T1 and T2), histological type (OR = 5.28 for diffuse type vs. tubular type), histological grade (OR = 3.09 for grade 3 vs. grades 1 and 2), TP53 status (OR = 0.55 for mutated vs. wild type), and PIK3CA status (OR = 0.55 for mutated vs. wild type) (all p < 0.05) by univariate logistic regression. Kaplan-Meier survival analysis showed high MSC-AS1 expression had a poor overall survival [hazard ratio (HR) = 1.75; 95% confidence interval (CI): 1.25–2.45; p = 0.001] and progression-free interval (HR = 1.47; 95% CI: 1.03–2.10; p = 0.034). Multivariate survival analysis revealed that MSC-AS1 expression (HR = 1.681; 95% CI: 1.057–2.673; p = 0.028) was independently correlated with overall survival. GSEA demonstrated that the P38/MAPK pathway, the VEGF pathway, the cell adhesion molecules cams, the NOD-like receptor signaling pathway were differentially enriched in the high MSC-AS1 expression phenotype. SsGSEA and Spearman correlation revealed the relationships between MSC-AS1 and macrophages, NK cells, and Tems were the strongest. Coregulatory proteins were included in the PPI network. Upregulated lncRNA MSC-AS1 might be a potential biomarker for the diagnosis and prognosis of gastric cancer.