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.

Identification and Validation of an EMT-Related LncRNA Signature for HNSCC to Predict Survival and Immune Landscapes

“…EMT is a process in which epithelial cells acquire mesenchymal cell characteristics and is closely related to tumor invasion, metastasis, and chemotherapy resistance in tumor progression ( Lamouille et al, 2014 ; Pastushenko and Blanpain, 2019 ; Xing et al, 2019 ; Guo et al, 2020 ). The molecular mechanisms involved in the transition from an epithelial phenotype to a mesenchymal state are complex and controlled by multiple signaling pathways ( Gugnoni and Ciarrocchi, 2019 ).…”

“…Long noncoding RNAs (lncRNAs) are defined as transcripts of more than 200 nucleotides that are not translated into proteins ( Xing et al, 2019 ; Guo et al, 2020 ). LncRNAs are crucial for cellular processes.…”

Integrative Analysis of LncRNAs and miRNAs, Revealing Key Biomarkers of Condyloma Acuminata

“…Studies have revealed that lncRNAs exerts key roles in cancer progression [19], and dysregulated lncRNAs were involved with the incidence of HPV-related diseases [20][21][22]. It was reported up-regulation of lncRNA FEZF1-AS1 facilitates cervical carcinoma via sponging miR-367-3p [23].…”

A Novel Ferroptosis-Related Gene Signature to Predict Prognosis in Patients with Head and Neck Squamous Cell Carcinoma

“…The 5year survival rate of patients with HNSCC is less than 50% [6], which is attributed to lack of reliable prognostic biomarkers [25]. Recent studies have established a correlation between molecular markers such as autophagy genes, immune genes, autophagy-associated long noncoding RNAs (lncRNAs), and immune-related lncRNAs, and HNSCC prognosis [26][27][28][29], which may aid in determining clinical outcomes.…”