Upregulated Expression of LncRNA Nicotinamide Nucleotide Transhydrogenase Antisense RNA 1 is Correlated with Unfavorable Clinical Outcomes in Cancers

Abstract

Background: The nicotinamide nucleotide transhydrogenase antisense RNA 1 (NNT-AS1) is a long non-coding RNA aberrantly expressed in human malignancies. We aimed to analyze available data to evaluate the correlation between NNT-AS1 expression and cancer prognosis. Methods: Literature retrieval was performed by systematic searching related databases from inception to April 2, 2020. Studies regarding correlation between NNT-AS1 expression, survival outcomes and clinical characteristics of cancer patients were collected and pooled to calculate the the hazard ratios (HRs) or odds ratios (ORs) with 95% confidence intervals (95% CIs). Results: Ten studies comprising 699 patients were included, all of which were conducted in China according to literature selection criteria. Overexpression of NNT-AS1 had a significant association with unfavorable overall survival (OS) (HR=2.08, 95% CI: 1.84-2.36, P<0.001). Stratified analysis showed that tumor type, sample size, follow-up months, and survival analysis approach did not change the predictive value of NNT-AS1 on OS. Furthermore, elevated NNT-AS1 level had significant association with distant metastasis (DM) (OR=2.45, 95% CI: 1.39-4.30), lymph node metastasis (LNM) (OR=3.92, 95% CI: 1.35-11.41), TNM stage (OR=4.25, 95% CI: 1.71-10.56), and vascular invasion (OR=3.98, 95% CI: 2.06-7.71), but was not associated with age and gender. The TCGA dataset further consistently showed that the NNT-AS1 expression was associated with poor OS and disease-free survival. Conclusions: High expression of NNT-AS1 is associated with unfavorable survival outcomes and poor clinicopathologic characteristics. However, large-cohort data and geographical studies are still needed to further validate the prognostic value of NNT-AS1 in cancers.