DUSP2 methylation is a candidate biomarker of outcome in head and neck cancer.

ABSTRACT: Background:Biomarkers predictive of response to chemoradiotherapy (CRT) regimens for locally advanced head and neck squamous cell carcinoma (LA-HNSCC) are urgently required to identify patients in whom this approach is likely to be effective. TP53 mutations and epidermal growth factor (EGFR) overexpression are common markers of disease. Dual-specificity-phosphatase-2 (DUSP2) has an essential role in cell proliferation, cancer and immune responses. Methods:Aberrant DUSP2 methylation was investigated by pyrosequencing in 5 HNSCC cell lines, 112 LA-HNSCC tumours. EGFR was investigated by immunohistochemistry and TP53 was analysed by sequencing. Results:We demonstrate methylation-dependent transcriptional silencing of DUSP2 in HNSCC cell lines. In LA-HNSCC patients, aberrant methylation in the DUSP2 CpG island was present in 51/112 cases (45.5%). LA-HNSCC cases with wild-type TP53, overexpression of EGFR and unmethylated DUSP2 had the worst overall survival (P?0.001). Conclusions:DUSP2 methylation, when combined with EGFR and TP53, is a candidate biomarker of clinical outcome in LA-HNSCC treated with CRT.

SUBMITTER: Lo Nigro C 

PROVIDER: S-EPMC6064804 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature