Abstract
Gastric cancer (GC) is the fourth most common malignant tumor. The mechanism underlying GC occurrence and development remains unclear. Previous studies have indicated that long non-coding RNAs (lncRNAs) are significantly associated with gastric cancer, but a systematic understanding of the role of lncRNAs in gastric cancer is lacking. In recent years, with the development of next-generation sequencing technology, tens of thousands of lncRNAs have been discovered. However, a large number of unannotated lncRNAs remain unidentified in different tissues, including potential gastric cancer-related lncRNAs. In this study, RNA sequencing (RNA-seq) data from 16 samples of eight gastric cancer patients were obtained and analyzed. A total of 1,854 previously unannotated lncRNAs were identified by ab initio assembly, and 520 differentially expressed lncRNAs were validated in the TCGA expression dataset. Methylation and copy number variation (CNV) array data from the same sample were integrated in the analysis. Changes in DNA methylation levels and CNVs may be responsible for the differential expression of 91 lncRNAs. Differentially expressed lncRNAs were enriched in coexpressed clusters of genes related to functions such as cell signaling, cell cycle, immune response, metabolic processes, angiogenesis, and regulation of retinoic acid (RA) receptors. Finally, a differentially expressed lncRNA, AC004510.3, was identified as a potential biomarker for the prediction of the overall survival of gastric cancer patients.
Highlights
Gastric cancer is the fourth most common malignant tumor in the world (Siegel et al, 2013)
A total of 92.6% of the 13,870 long non-coding RNAs (lncRNAs) (23,898 transcripts) annotated in GENCODE v19 were detected in gastric cancer and paracancerous healthy tissue samples, which indicates that the sequencing depth of the RNA sequencing (RNA-seq) dataset was sufficient for studying the function of lncRNAs in gastric cancer
We found that the expression level of 90 differentially expressed lncRNAs correlated with DNA methylation signals in the corresponding promoter region
Summary
Gastric cancer is the fourth most common malignant tumor in the world (Siegel et al, 2013). Identifying important regulatory molecules in gastric cancer can provide valuable information for finding biomarkers for diagnosis and prognosis and for therapeutic targets. Expressed lncRNAs have been found in common malignant tumors, such as liver cancer and breast cancer (Eades et al, 2014; Amorim et al, 2016; Yang et al, 2017). These lncRNA Analysis in Gastric Cancer lncRNAs regulate tumor cells via various signaling pathways, such as Notch, mTOR, NF-κB, Wnt, and TGF-β, and play an important role in cell division, differentiation, apoptosis, invasion, and other processes (Song et al, 2013; Li et al, 2015; Cheng et al, 2019a). Compared with mRNA, lncRNA expression is more tissue specific (Tsoi et al, 2015; Cheng et al, 2018, 2019c; Cheng, 2019), which may provide new information for finding specific biomarkers for gastric cancer
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