| Objective:1. To detecting MGMT promoter methylation in peripheral blood and cerebrospinal fluid(CSF),and compared to the corresponding tumor tissue collected from glioma patients;2. To evaluate the sensitivity and specificity of detecting MGMT promoter methylation in CSF and serum;3. To evaluate the relationship between sensitivity and specificity of detecting MGMT promoter methylation in CSF and serum and various clinicopathology factorsMethods:The clinicopathologic data of 89 glioma patients(32 WHO II?19 WHO III and 38 WHO IV) were analyzed retrospectively. All the patients were were pathologically-diagnosed glioma and received radiation therapy following sample collection. The resected glioma tumor tissue(89 samples) and corresponding serum(n=89) and CSF(n=78) samples were collected in Tianjin huanhu Hosptial.(1)To analyze the clinical and pathological(tissue?CSF and serum) data for all patients;(2)The MGMT promoter methylation of tumor tissue and compared serum/CSF were detected by methylation-specific Polymerase Chain Reaction(PCR);(3)To evaluate the sensitivity and specificity of detecting MGMT promoter methylation in CSF and serum;(4)To evaluate the relationship between sensitivity and specificity of detecting MGMT promoter methylation in CSF/serum and degree of surgical resection and grade of tumor; Count data were compared using chi square test and Fisher's exact test. A P<0.05 was considered statistically significant. All statistical were done using SPSS16.0 software program.Results:1. Among the tumor tissue samples, 57.3%(51/89) showed MGMT promoter methylation; further subgroup analysis revealed that the proportions of MGMT promoter methylation in the tumor tissue sample of WHO II, III and IV glioma were 65.6%?57.9% and 50.0%, respectively;2. To further assess the sensitivity of testing MGMT promoter methylation in serum versus CSF, the specific results were analyzed for the 51 tumor tissues that tested positive for MGMT promoter methylation. Of these 51 positive samples, 51 matched serum samples and 40 matched CSF samples were collected. The overall sensitivity of MGMT promoter methylation detection was higher for CSF 65.0%(26/40) than for serum 37.3%(19/51),the difference between them was statistically significant(P <0.05).For serum and CSF, the specificity reached 100%, none of the tumor tissue samples that tested negative for MGMT promoter methylation had corresponding CSF or blood samples that tested positive.3. Subgroup analysis revealed that the sensitivity using CSF in WHO II, III and IV glioma patients(66.7%,61.1% and 70.0% respectively) was significantly higher than the corresponding values obtained using serum(33.3%, 36.8%; and 45.5%, respectively) the difference between them was statistically significant(P <0.05), thus verifying the uniformly higher sensitivity of the CSF samples.4. Among the 38 patients who had no residual tumors, as assessed by magnetic resonance imaging, the sensitivity of detecting MGMT promoter methylation using CSF and serum was 8/15(53.3%) and 6/19(31.6%), respectively. The sensitivity of detecting MGMT promoter methylation for the ‘residual tumor' group(72.0% for CSF; 41.7% for blood) was significantly higher than for the ‘no residual tumor' group(53.3% for CSF; 31.6% for serum), the difference between them was statistically significant(P <0.05).Conclusion:1. MGMT promoter methylation of circulating DNA in serum and CSF was successfully applied to patients with different levels of glioma2. CSF specimens show higher specificity than serum for detecting MGMT promoter methylation in patients with glioma. The results show a good prospect of using CSF specimens for the detection of circulating DNA in tumors of the nervous system. Assessment of MGMT promoter methylation in CSF may provide a promising clinical methodology for early diagnosis, design of individualized treatment plans, monitoring of recurrence and prognosis of glioma patients. |
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