Abstract
BackgroundOur 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.Patients and methodsSLC22A18 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.ResultsSLC22A18 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.ConclusionsThese results show that lack of SLC22A18 protein expression is superior to promoter methylation as a predictive tumor biomarker in GBM patients receiving temozolomide therapy.
Highlights
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)
We have found that the elevated expression of SLC22A18 was found to increase the sensitivity of glioma U251 cells to the anticancer drug 1,3bis(2-chloroethyl)-1-nitrosourea (BCNU) [12]
In all cell cultures SLC22A18 protein expressions were successfully analyzed by Western blotting (Figure 1C). 36 of the 86 cases (42%) were scored positive for SLC22A18 protein expression based on a visible band and corresponding to a relative expression level > 0.1
Summary
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). Glioblastoma multiforme (GBM) is the most common and lethal glial tumor of the adult brain, accounting for about fifty percent of all gliomas. It is characterized by an aggressive growth pattern, a marked degree of the invasiveness and very poor prognosis. We have previously found that SLC22A18 downregulation and promoter methylation were associated with the development and progression of glioma and SLC22A18 represented a candidate biomarker for long-term survival in this disease, suggesting that SLC22A18 is an important tumor suppressor in glioma [10,11]. We have found that the elevated expression of SLC22A18 was found to increase the sensitivity of glioma U251 cells to the anticancer drug 1,3bis(2-chloroethyl)-1-nitrosourea (BCNU) [12]
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