title: Predictive value of the SLC22A18 protein expression in glioblastoma patients receiving temozolomide therapy.
abstract: BACKGROUND
  Our previous study showed that SLC22A18 downregulation and promoter methylation were associated with the development and progression of glioma and the elevated expression of SLC22A18 was found to increase the sensitivity of glioma U251 cells to the anticancer drug 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU). In this study, we investigated the predictive value of SLC22A18 promoter methylation and protein expression in glioblastoma multiforme (GBM) patients receiving temozolomide (TMZ) therapy.
  
  
  METHODS
  SLC22A18 promoter methylation and protein expression were examined by methylation-specific polymerase chain reaction (MSP) and Western blotting respectively, then we compared SLC22A18 promoter methylation and protein expression in tumor cell explants in regard to prediction of TMZ response and survival time of 86 GBM patients.
  
  
  RESULTS
  SLC22A18 promoter methylation was detected in 61 of 86 (71%) samples, whereas 36 of 86 (42%) cases were scored positive for SLC22A18 protein expression. Overall SLC22A18 promoter methylation was significantly related to SLC22A18 protein expression, but a subgroup of cases did not follow this association. Multivariate Cox regression analysis indicated that SLC22A18 protein expression, but not promoter methylation, was significantly correlated with TMZ therapy. SLC22A18 protein expression predicted a significantly shorter overall survival in 51 patients receiving TMZ therapy, whereas no differences in overall survival were observed in 35 patients without TMZ therapy.
  
  
  CONCLUSIONS
  These results show that lack of SLC22A18 protein expression is superior to promoter methylation as a predictive tumor biomarker in GBM patients receiving temozolomide therapy.
authors.affiliation: Department of Neurosurgery, Shanghai 3rd People's Hospital, School of Medicine, Shanghai Jiao Tong University, 280 Mohe Road, Baoshan District, Shanghai 201900, China. shenghuachu@126.com.
authors.forename: Sheng-Hua
authors.initials: SH
authors.lastname: Chu
authors.forename: Yan-Bin
authors.initials: YB
authors.lastname: Ma
authors.forename: Dong-Fu
authors.initials: DF
authors.lastname: Feng
authors.forename: Zhi-Qiang
authors.initials: ZQ
authors.lastname: Li
authors.forename: Pu-Cha
authors.initials: PC
authors.lastname: Jiang
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D015153:Blotting, Western; D001932:Brain Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D019175:DNA Methylation; D003606:Dacarbazine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005260:Female; D005909:Glioblastoma / Q000188:drug therapy / Q000378:metabolism*; D006801:Humans; D008297:Male; D027701:Organic Cation Transport Proteins / Q000235:genetics / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D000077204:Temozolomide
chemical_list: D000970:Antineoplastic Agents; D027701:Organic Cation Transport Proteins; C111653:SLC22A18 protein, human; D003606:Dacarbazine; D000077204:Temozolomide