Expression of LINC00312, a long intergenic non-coding RNA, is negatively correlated with tumor size but positively correlated with lymph node metastasis in nasopharyngeal carcinoma

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Abstract
The long intergenic non-coding RNA LINC00312, also called NAG7, was first cloned by our group. Our previous studies have found that LINC00312 could inhibit proliferation and induce apoptosis in nasopharyngeal carcinoma (NPC) cells but also stimulate NPC cell invasion. However, the relevance of LINC00312 in NPC progression or in patient outcomes has not been reported. This study aims to assess the possible correlations of LINC00312 expression with NPC progression and its potential prognostic predictive ability in NPC outcomes. A NPC tissue microarray, which included 561 normal and NPC tissue cores, was used to detect LINC00312 expression, and we found that LINC00312 was significantly down-regulated in NPC tissues compared with non-cancerous nasopharyngeal epithelium tissues. Positive expression of LINC00312 was negatively correlated with tumor size (P < 0.001) but positively correlated with lymph node metastasis (P = 0.002). A receiver operating characteristic (ROC) analysis revealed that LINC00312 expression could distinguish non-cancerous patients from NPC patients (P < 0.001, sensitivity: 72.1 %, specificity: 87.7 %). We also found that LINC00312 was strongly negatively correlated with EBER-1, a non-coding RNA transcribed by Epstein-Barr Virus, in NPC (r = −0.384, P < 0.001). In the final logistic regression analysis model, the abnormal expression of LINC00312 and EBER-1 were found to be independent contributors to nasopharyngeal carcinogenesis (P < 0.001, P < 0.001, respectively). A survival analysis revealed that LINC00312 could predict a good prognosis of no lymph node metastasis (Disease Free Survival (DFS): P = 0.005, Overall Survival (OS): P = 0.001) and a poor prognosis of lymph node metastasis (DFS: P = 0.011, OS: P = 0.001) in NPC patients. Low expression of LINC00312 was an independent risk factor for OS in multivariate analyses (P = 0.017). These observations indicated that LINC00312 could represent a potential biomarker for metastasis, progression and prognosis in NPC.

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