DUSP2 methylation is a candidate biomarker of outcome in head and neck cancer.
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.
['Lo Nigro|Cristiana|C|', 'Vivenza|Daniela|D|', 'Denaro|Nerina|N|', 'Lattanzio|Laura|L|', 'Fortunato|Mirella|M|', 'Crook|Tim|T|', 'Merlano|Marco Carlo|MC|']
biomarkers Head and neck cancer dual-specificity-phosphatase-2 (DUSP2) epigenetics