Genome-wide analysis of long non-coding RNAs in esophageal squamous cell carcinoma reveals their potential role in invasion and metastasis.

BACKGROUND: A high lymphatic metastasis rate and strong local invasive ability are the key characteristics of esophageal squamous cell carcinoma (ESCC) that affect patient survival, and long non-coding RNAs (lncRNAs) may play a crucial role. We performed genome-wide analysis of lncRNAs to identify novel biomarkers associated with local invasion and lymphatic metastasis in ESCC.

METHODS: Six pairs of ESCC tumor and para-tumor tissues were subjected to microarray analysis to identify differentially expressed lncRNAs, and 25 pairs of tissues samples were used to verify the effectiveness of screened lncRNAs using quantitative reverse transcription PCR. The correlations between verified lncRNAs and clinicopathological characteristics were analyzed to confirm specific lncRNAs associated with the local invasion and lymphatic metastasis of ESCC, and gene co-expression analysis was used to predict potential mechanisms.

RESULTS: Microarray analysis identified 1850 lncRNAs with significant differential expression in ESCC. Of 22 lncRNAs selected for quantitative reverse transcription PCR verification, four were significantly upregulated and one was significantly downregulated in ESCC cancer compared to para-cancer tissues. ENST00000508406.1 was significantly associated with T, N, and tumor node metastasis stages, and NR_037652.1 was significantly associated with N stage. Moreover, 49 lncRNA-messenger RNA pairs were significantly associated with the two dysregulated lncRNAs and possibly involved in the regulation of local invasion and lymphatic metastasis of ESCC.

CONCLUSION: The present genome-wide analysis identified two novel and tumor-specific lncRNAs for predicting ESCC local invasion and lymphatic metastasis, providing insight into the potential underlying mechanism, which warrants further investigation.