Testing lncRNAs signature as clinical stage–related prognostic markers in gastric cancer progression using TCGA database

Author:

Beeraka Narasimha M12,Gu Hao13,Xue Nannan13,Liu Yang4,Yu Huiming5,Liu Junqi13ORCID,Chen Kuo1,Nikolenko Vladimir N26,Fan Ruitai13ORCID

Affiliation:

1. Cancer Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China

2. Department of Human Anatomy, I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University), Moscow 119991, Russia

3. Department of Radiation Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China

4. Department of Radiotherapy, Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou 450052, China

5. Department of Radiation Oncology, Peking University Cancer Hospital & Institute, Beijing 450052, China

6. M.V. Lomonosov Moscow State University, Moscow, 119991, Russia

Abstract

LncRNA expression can be conducive to gastric cancer (GC) prognosis. The objective of this study is to ascertain five specific lncRNAs involved in tumor progression of GC and their role as prognostic markers to diagnose clinical stage-wise GC. High-throughput RNA sequencing data were obtained from The Cancer Genome Atlas (TCGA) database and performed genome-wide lncRNA expression analysis using edgeR package, Bioconductor.org , and R-statistical computing to analyze differentially expressed lncRNA analysis. Cutoff parameters were FDR < 0.05 and |Log2FC| > 2. Total 351 tumor samples with differentially expressed lncRNAs were divided into group-1 lncRNAs such as AC019117.2 and LINC00941, and group-2 lncRNAs such as LINC02410, AC012317.2, and AC141273.1 by 2:1. The Spearman correlation coefficients ( p < 0.05) and correlation test function (cor.test ()) were performed for lncRNAs as per clinical stage. Cytoscape software was used to construct lncRNA–mRNA interaction networks. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway ( p < 0.05) analysis were conducted using the clusterProfiler package. Kaplan–Meier survival analysis was performed to determine the overall survival of patients based on the expression of five lncRNAs in different clinical stages of GC. AC019117.2 and LINC00941 of group 1 inferred a positive correlation with clinical stages of stage I to stage IV, and their expressions were higher in tumor tissues than normal tissues. On the contrary, LINC02410, AC012317.2, and AC141273.1 of group 2 exhibited a negative correlation with clinical stage, and they exhibited more expression in normal tissues compared to tumor tissues. GO and KEGG pathway analysis reported that AC019117.2 may interact with LINC00941 via ITGA3 and trophoblast glycoprotein (TPBG) to foster tumor progression. Tumor-specific group-1 lncRNAs were conducive to the poor overall survival and exhibited a positive correlation with the clinical stages of stage I to stage IV in GC as per the lncRNA–mRNA networking analysis. These five lncRNAs could be considered as clinically useful lncRNA-based prognostic markers to predict clinical stage-wise GC progression.

Funder

National Natural Science Foundation of China

Russian Academic Excellence project “5-100” for the Sechenov University

GALLY International Research Institute

Publisher

SAGE Publications

Subject

General Biochemistry, Genetics and Molecular Biology

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