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.
Highlights
Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer in the world and accounts for more than 90% of head and neck cancers [1]
A total of 14,142 long non-coding RNAs (lncRNAs) were identified by analyzing RNA sequence data from HNSCC patient tissue samples in the TCGA database, and 232 Autophagy-related genes (ATGs) were extracted from the Human Autophagy Database (Supplementary Material 2)
In multivariate Cox regression analysis three autophagy-related lncRNAs were significantly correlated with HNSCC prognosis; AL121899.1, TTTY15, and MIF-AS1 (Figure 1C)
Summary
Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer in the world and accounts for more than 90% of head and neck cancers [1]. Advances in surgical treatment combined with radiotherapy, chemotherapy, or biotherapy have resulted in improved HNSCC prognoses, but advanced-stage HNSCC is still associated with an unfavorable prognosis and a high mortality rate [2, 3]. Autophagy is a self-degradative process that maintains cellular homeostasis. It plays complex roles at different stages of tumorigenesis, and it may promote oncogenesis in some contexts but participate in tumor suppression in others [5]. Clarifying the mechanisms involved in autophagy may contribute to the development of new cancer treatment strategies. Several studies suggest that inhibiting autophagy in patients with advanced cancers may enhance the treatment of malignancy, and that the promotion of autophagy in HNSCC can protect cells [6]. Further attention to elucidate the roles and clarify the mechanisms of autophagy in HNSCC is needed
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