Seven-CpG-based prognostic signature coupled with gene expression predicts survival of oral squamous cell carcinoma

Abstract

BackgroundDNA methylation has started a recent revolution in genomics biology by identifying key biomarkers for multiple cancers, including oral squamous cell carcinoma (OSCC), the most common head and neck squamous cell carcinoma.MethodsA multi-stage screening strategy was used to identify DNA-methylation-based signatures for OSCC prognosis. We used The Cancer Genome Atlas (TCGA) data as training set which were validated in two independent datasets from Gene Expression Omnibus (GEO). The correlation between DNA methylation and corresponding gene expression and the prognostic value of the gene expression were explored as well.ResultsThe seven DNA methylation CpG sites were identified which were significantly associated with OSCC overall survival. Prognostic signature, a weighted linear combination of the seven CpG sites, successfully distinguished the overall survival of OSCC patients and had a moderate predictive ability for survival [training set: hazard ratio (HR) = 3.23, P = 5.52 × 10−10, area under the curve (AUC) = 0.76; validation set 1: HR = 2.79, P = 0.010, AUC = 0.67; validation set 2: HR = 3.69, P = 0.011, AUC = 0.66]. Stratification analysis by human papillomavirus status, clinical stage, age, gender, smoking status, and grade retained statistical significance. Expression of genes corresponding to candidate CpG sites (AJAP1, SHANK2, FOXA2, MT1A, ZNF570, HOXC4, and HOXB4) was also significantly associated with patient’s survival. Signature integrating of DNA methylation, gene expression, and clinical information showed a superior ability for prognostic prediction (AUC = 0.78).ConclusionPrognostic signature integrated of DNA methylation, gene expression, and clinical information provides a better prognostic prediction value for OSCC patients than that with clinical information only.Electronic supplementary materialThe online version of this article (doi:10.1186/s13148-017-0392-9) contains supplementary material, which is available to authorized users.

Oncogenic drivers in 11q13 associated with prognosis and response to therapy in advanced oropharyngeal carcinomas

“…Amplification and overexpression of SHANK2 was also associated with poor prognosis in esophageal squamous cell carcinoma [58]. In oral carcinomas, SHANK2 was described as one of seven prognostic markers evaluated by DNA methylation [59]. These finding suggest that CNA and/or epigenetic mechanisms may result in SHANK2 increased expression and consequent HNSCC aggressiveness.…”

Establishment of epigenetic markers to predict irradiation efficacy against oropharyngeal cancer

“…In that report, we also showed a significant association between DNA methylation of gene promoters (eg RXRG ) and better prognosis in HNSCC . Shen et al proposed a prognosis prediction algorithm based on methylome and transcriptome data from clinical specimens of oral squamous cell carcinoma. The results suggest that aberrant DNA methylation could help to predict HNSCC prognosis or the efficacy of the therapies against this disease.…”

Discovery and development of differentially methylated regions in human papillomavirus‐related oropharyngeal squamous cell carcinoma

“…Of the 20 candidates confirmed by multiple confirmation steps, ITGA4 (integrin subunit alpha 4) has previously been found hypermethylated in OPSCC, 29 and NID2 (nidogen 2) and HOXB4 (homeobox B4) have previously been found hypermethylated and downregulated in oral squamous cell carcinoma (OSCC). 27,30 The functional roles of ITGA4, NID2 and HOXB4 have not been investigated in HNSCC. However, in chronic lymphocytic leukemia ITGA4 on the surface of cells facilitates migration and adhesion to the microenvironment.…”