Work

Reduced promoter methylation and increased expression of CSPG4 negatively influences survival of HNSCC patients

Year: 2014

Type: article

Abstract: 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.

Source: International Journal of Cancer

DOI: 10.1002/ijc.28906

Authors: Rolf Warta, Christel Herold‐Mende, Jittiporn Chaisaingmongkol, Odilia Popanda, Andreas Mock, Carolin Mogler, Florian Osswald, Esther Herpel, Sabine Küstner, Volker Eckstein, Christoph Plass, Peter Plinkert, Peter Schmezer, Gerhard Dyckhoff

Institutions: Heidelberg University, German Cancer Research Center, National Center for Tumor Diseases

Language: English

Topic: Proteoglycans and glycosaminoglycans research

Subfield: Cell Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: bronze

OpenAlex ID: W1568432012

FWCI: 1.89

Cites: 33

Cited by: 51

Related to: 10