Abstract. Abnormal expression of long non-coding RNAs (lncRNAs) have been shown to play an important role in tumor biology. The Cancer Genome Atlas (TCGA) platform is a large sample sequencing database of lncRNAs, and further analysis of the associations between these data and patients' clinical related information can provide new approaches to find the functions of lncRNA. In the present study, 361 RNA sequencing profiles of gastric cancer (GC) patients were selected from TCGA. Then, we constructed the lncRNA-miRNA-mRNA competitive endogenous RNA (ceRNA) network of GC. There were 25 GC specific lncRNAs (fold change >2, p<0.05) identified, 19 of them were included in ceRNA network. Subsequently, we selected these 19 key lncRNAs and analyzed the correlations with clinical features and overall survival, 14 of them were discriminatively expressed with tumor size, tumor grade, TNM stage and lymphatic metastasis (p<0.05). In addition, eight lncRNAs (RPLP0P2, FOXD2-AS1, H19, TINCR, SLC26A4-AS1, SMIM10L2A, SMIM10L2B and SNORD116-4) were found to be significantly associated with overall survival (log-rank p<0.05). Finally, two key lncRNAs HOTAIR and UCA1 were selected for validation of their expression levels in 82 newly diagnosed GC patients by qRT-PCR. Results showed that the fold changes between TCGA and qRT-PCR were 100% in agreement. In addition, we also found that HOTAIR was significantly correlated with tumor size and lymphatic metastasis (p<0.05), and UCA1 was significantly correlated with tumor size, TNM stage and lymphatic metastasis (p<0.05).The clinical relevance of the two lncRNAs and the bioinformatics analysis results were almost the same. Overall, our study showed the GC specific lncRNAs expression patterns and a ceRNA network in GC. Clinical features related to GC specific lncRNAs also suggested these lncRNAs are worthwhile for further study as novel candidate biomarkers for the clinical diagnosis of GC and potential indicators for prognosis.
IntroductionNoncoding RNAs (ncRNAs) are transcripts that have no ability of coding proteins, which widely exit in high eukaryotics. According to their characteristics, ncRNAs can be divided into several subtypes including transfer RNA, small nucleolar RNA (snoRNA), ribosomal RNA (rRNA), microRNA (miRNA) and long non-coding RNA (lncRNA). The amount of the ncRNAs transcripts is >98% of the whole genome transcripts and have been suggested to represent transcriptional noise (1). However, more and more evidence indicates that transcriptional output of genome is far more complex than predicted, and suggests new paradigms of ncRNA regulation (2).Recent studies suggest that the ncRNAs may play important biological roles in transcriptional regulation, cellular development, formation of chromosome and RNA modification (3). Based on the transcript size, ncRNAs are grouped into small ncRNAs (<200 bp) and long ncRNAs (>200 bp, up to 100 kb). lncRNA is the functional end-product, and the level of lncRNA expression correlates directly with the level of the active molecule. Thus, ...