Abstract
Oral squamous cell carcinoma (OSCC) is a major malignant cancer of the head and neck. Long non-coding RNAs (lncRNAs) have emerged as critical regulators during the development and progression of cancers. This study aimed to identify a lncRNA-related signature with prognostic value for evaluating survival outcomes and to explore the underlying molecular mechanisms of OSCC. Associations between overall survival (OS), disease-free survival (DFS) and candidate lncRNAs were evaluated by Kaplan–Meier survival analysis and univariate and multivariate Cox proportional hazards regression analyses. The robustness of the prognostic significance was shown via the Gene Expression Omnibus (GEO) database. A total of 2,493 lncRNAs were differentially expressed between OSCC and control samples (fold change >2, p < 0.05). We used Kaplan–Meier survival analysis to identify 21 lncRNAs for which the expression levels were associated with OS and DFS of OSCC patients (p < 0.05) and found that down-expression of lncRNA AC012456.4 especially contributed to poor DFS (p = 0.00828) and OS (p = 0.00987). Furthermore, decreased expression of AC012456.4 was identified as an independent prognostic risk factor through multivariate Cox proportional hazards regression analyses (DFS: p = 0.004, hazard ratio (HR) = 0.600, 95% confidence interval(CI) [0.423–0.851]; OS: p = 0.002, HR = 0.672, 95% CI [0.523–0.863). Gene Set Enrichment Analysis (GSEA) indicated that lncRNA AC012456.4 were significantly enriched in critical biological functions and pathways and was correlated with tumorigenesis, such as regulation of cell activation, and the JAK-STAT and MAPK signal pathway. Overall, these findings were the first to evidence that AC012456.4 may be an important novel molecular target with great clinical value as a diagnostic, therapeutic and prognostic biomarker for OSCC patients.
Highlights
The five-year survival rate is approximately 50% for oral squamous cell carcinoma (OSCC), which is one of the most common malignancies of the head and neck region (Bozec et al., How to cite this article Hu et al (2018), A novel long non-coding RNA, AC012456.4, as a valuable and independent prognostic biomarker of survival in oral squamous cell carcinoma
Characteristics of Oral squamous cell carcinoma (OSCC) patients according to the The Cancer Genome Atlas (TCGA)
The datasets of 350 OSCC patient and 44 controls were acquired and downloaded from the TCGA database; these datasets contained expression data and clinical information related to 14,448 Long non-coding RNAs (lncRNAs)
Summary
The five-year survival rate is approximately 50% for oral squamous cell carcinoma (OSCC), which is one of the most common malignancies of the head and neck region (Bozec et al., How to cite this article Hu et al (2018), A novel long non-coding RNA, AC012456.4, as a valuable and independent prognostic biomarker of survival in oral squamous cell carcinoma. The Cancer Genome Atlas (TCGA) (http://cancergenome.nih.gov) database, which is primarily used to collate specimens from cancer patients and adjacent normal tissue specimens, contains large data sets collected with high-throughput methods at multiple genomic and proteomic levels (Chin, Andersen & Futreal, 2011; Wang, Gerstein & Snyder, 2009). The Gene Expression Omnibus (GEO, http://www.ncbi.nlm.nih.gov/geo/) is the largest and most comprehensive public gene expression repository for high-throughput data at NCBI (Barrett & Edgar, 2006; Clough & Barrett, 2016). Both the GEO and TCGA collect macroscopic clinical information, such as stage and grade of tumor, survival time, age, sex, and race. The TCGA and GEO databases can be analyzed systematically and comprehensively to explore important potential value and information
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