Identification of Three Autophagy-Related Long Non-Coding RNAs as a Novel Head and Neck Squamous Cell Carcinoma Prognostic Signature

Abstract

Head and neck squamous cell carcinoma (HNSCC) has a poor prognosis. Considerable evidence indicates that autophagy and non-coding RNA play essential roles in the biological processes involved in cancers, but associations between autophagy-related long non-coding RNAs (lncRNAs) and HNSCC remain unclear. In the present study, HNSCC RNA sequences and autophagy-related gene data were extracted from The Cancer Genome Atlas database and the Human Autophagy Database. A total of 1,153 autophagy-related lncRNAs were selected via calculating Pearson's correlation coefficient. Three prognosis-related autophagy lncRNAs were identified via univariate Cox regression, least absolute shrinkage and selection operator analysis, and multivariate Cox regression analysis. We also constructed a prognostic model based on these autophagy-related lncRNAs and evaluated its ability to accurately and independently predict the prognosis of HNSCC patients. The area under the curve (AUC) was 0.864 (3-year) and 0.836 (5-year), and our model can independently predict the prognosis of HNSCC. The prognostic value of the three autophagy lncRNAs was confirmed via analysis of samples from five databases. To further identify the functions of the three lncRNAs, a co-expression network was constructed and pathway analysis was performed. In that analysis the lncRNAs were correlated with 189 related genes and 20 autophagy-related genes, and these lncRNAs mainly involved homologous recombination, the Fanconi anemia pathway, the autophagy-related pathway, and immune-related pathways. In addition, we validated the expression levels of three lncRNAs and autophagy markers (ATG12, BECN1, and MAP1LC3B) based on TIMER, Oncomine, and HPA database analysis. Our results indicated that TTTY15 was increased in HPV positive and HPV negative HNSCC patients, and three autophagy markers were up-regulated in all HNSCCC patients. Lastly, association between three lncRNAs and autophagy markers was performed, and our results showed that TTTY15 and MIF-AS1 were associated with autophagy markers. Collectively, these results suggested that three autophagy-related lncRNAs have prognostic value in HNSCC patients.

Keywords: The Cancer Genome Atlas; autophagy; head and neck squamous cell carcinoma; long non-coding RNA; prognosis.