title: Reduced promoter methylation and increased expression of CSPG4 negatively influences survival of HNSCC patients.
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.
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery, University of Heidelberg, Heidelberg, Germany; Division of Experimental Neurosurgery, Department of Neurosurgery, University of Heidelberg, Heidelberg, Germany.
authors.forename: Rolf
authors.initials: R
authors.lastname: Warta
authors.forename: Christel
authors.initials: C
authors.lastname: Herold-Mende
authors.forename: Jittiporn
authors.initials: J
authors.lastname: Chaisaingmongkol
authors.forename: Odilia
authors.initials: O
authors.lastname: Popanda
authors.forename: Andreas
authors.initials: A
authors.lastname: Mock
authors.forename: Carolin
authors.initials: C
authors.lastname: Mogler
authors.forename: Florian
authors.initials: F
authors.lastname: Osswald
authors.forename: Esther
authors.initials: E
authors.lastname: Herpel
authors.forename: Sabine
authors.initials: S
authors.lastname: Küstner
authors.forename: Volker
authors.initials: V
authors.lastname: Eckstein
authors.forename: Christoph
authors.initials: C
authors.lastname: Plass
authors.forename: Peter
authors.initials: P
authors.lastname: Plinkert
authors.forename: Peter
authors.initials: P
authors.lastname: Schmezer
authors.forename: Gerhard
authors.initials: G
authors.lastname: Dyckhoff
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000401:mortality* / Q000473:pathology; D016022:Case-Control Studies; D011508:Chondroitin Sulfate Proteoglycans / Q000235:genetics* / Q000378:metabolism*; D018899:CpG Islands; D019175:DNA Methylation; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic; D006258:Head and Neck Neoplasms / Q000235:genetics / Q000401:mortality* / Q000473:pathology; D006801:Humans; D007124:Immunoenzyme Techniques; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism*; D009367:Neoplasm Staging; D011379:Prognosis; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D014407:Tumor Cells, Cultured; D055815:Young Adult; D000099216:Chondroitin Sulfate Proteoglycan 4
chemical_list: D011508:Chondroitin Sulfate Proteoglycans; D008565:Membrane Proteins; D012333:RNA, Messenger; C101390:CSPG4 protein, human; D000099216:Chondroitin Sulfate Proteoglycan 4
keywords: CSPG4 methylation and expression; HNSCC; survival