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Reduced promoter methylation and increased expression of CSPG4 negatively influences survival of HNSCC patients
Author(s) -
Warta Rolf,
HeroldMende Christel,
Chaisaingmongkol Jittiporn,
Popanda Odilia,
Mock Andreas,
Mogler Carolin,
Osswald Florian,
Herpel Esther,
Küstner Sabine,
Eckstein Volker,
Plass Christoph,
Plinkert Peter,
Schmezer Peter,
Dyckhoff Gerhard
Publication year - 2014
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.28906
Subject(s) - dna methylation , cancer research , methylation , cpg site , biology , gene expression , gene , genetics
Proteoglycans are often overexpressed in tumors and can be found on several normal and neoplastic stem cells. In this study, we analyzed in‐depth the role of CSPG4 in head and neck squamous cell carcinomas (HNSCC). Analysis of CSPG4 in a homogeneous study sample of HPV‐negative stage IVa HNSCCs revealed overexpression of protein and mRNA levels in a subgroup of HNSCC tumors and a significant association of high CSPG4 protein levels with poor survival. This could be validated in three publicly available microarray datasets. As a potential cause for upregulated CSPG4 expression, we identified DNA hypomethylation in a CpG‐island of the promoter region. Accordingly, we found an inverse correlation of methylation and patient outcome. Finally, CSPG4 re‐expression was achieved by demethylating treatment of highly methylated HNSCC cell lines establishing a direct link between methylation and CSPG4 expression. In conclusion, we identified CSPG4 as a novel biomarker in HNSCC on several biological levels and established a causative link between DNA methylation and CSPG4 protein and mRNA expression.