Promoter methylation status of MGMT, hMSH2, and hMLH1 and its relationship to corresponding protein expression and TP53 mutations in human esophageal squamous cell carcinoma.
The authors retrospectively analyzed the hypermethylation status of 11 genes using methylation-specific polymerase chain reaction (PCR) and the expression of epidermal growth factor receptor (EGFR), O-6 methylguanine-DNA methyltransferase (MGMT), tumor protein 53 (p53), and transforming growth factor β (TGFβ) using immunohistochemistry in 329 formalin-fixed, paraffin-embedded ESCCs.
Our study found the P16, MGMT and hMLH1 demonstrate a high proportion of hypermethylation in esophageal squamous cell cancer cancer tissues, which might be used as biomarkers for cancer detection.
Increased risk of ESCC metastasis was indicated in MGMT for frequency of presence C allele [Rs7068306: 2.204 (1.244-3.906)], A allele [Rs10734088: 1.968 (1.111-3.484)] and C allele [Rs4751115: 2.178 (1.251-3.791)].
The A allele of the rs7087131 variant of MGMT gene was associated with a decreased risk of ESCC under a dominant model (odds ratio, 0.79; 95% confidence interval, 0.64-0.96; P = 0.02).
The expression levels of four genes (hMSH2, XRCC1, XPD, MGMT) present in PBMC were significantly correlated with increased risk for ESCC, in which there was reduced expression of MGMT, suggesting an important etiology role for MGMT expression in the initiation of ESCC in Huaian of China.
In the ESCC cell line KYSE 510, treatment with a DNA methyltransferase inhibitor, 2'-deoxy-5-azacytidine partially reversed the CpG hypermethylation status and restored mRNA expression of the MGMT gene.
Fifty-one percent (61/119) ESCC showed p53 mutations but the distribution of the mutations did not differ significantly between MGMT-methylated ESCC (44%) and MGMT-unmethylated ESCC (56.2%; P = 0.18).