| Background and objectiveEsophageal cancer is one of common malignant tumors in China. Despite considerable advancement of therapeutic strategies, the mortality rate of esophageal cancer remains high. Given that the majority of patients are bearing advanced esophageal cancer at the time of diagnosis, surgical resection can only achieve a 25-40% 5-year survival, but resulting in a 90% 5-year survival rate in patients with early esophageal cancer. Accordingly, early detection and early management are beneficial to improve treatment efficacy and prolong patient survival. The cytology and endoscopy, as two main methods for early diagnosis of digestive tract cancer, are not applicable to large-scale population screening due to their intrinsic disadvantages. Therefore, accumulating researches have focused on identifying more handy and sensitive serum tumor biomarkers, among which the detection of circulating DNA methylation showed good prospects. DNA methylation is an important way of epigenetic modification. DNA hypermethylation remodels chromatin conformation to inactivate the transcription of tumor suppressor genes, playing crucial role on embryonic development and tumorigenesis. CpG island hypermethylation, usually preceding other genetic and biological changes, is a frequent early event during carcinogenesis of various types of cancers, suggesting that CpG island hypermethylation might provide important information for early detection of cancer. In addition, circulating tumor cells (CTCs) and free DNA fragments releasing from the necrotic tumor cells share the same genetic alteration with primary lesion and could be detected in peripheral blood, bronchoalveolar lavage, sputum, urine and other clinical samples, implying that they might be useful as a potential marker for cancer diagnosis and monitor. Runt-related transcription factor 3 (RUNX3), a newly identified candidate tumor suppressor gene, which is located on Ip36.1,is an important component of transforming growth factor beta (TGF-β) signal pathway. Recent studies have demonstrated that the down-regulation or silencing of RUNX3 gene closely associated with digestive tract cancer and the mechanism of its inactivation may be hypermethylation of the promoter. In this study we detected the serum aberrant methylation status of RUNX3 promoter region in patients with esophageal squamous cell carcinoma and analyzed its relationship with clinicopathological features in order to provide a potential new marker for the early diagnosis of cancer and screening of high-risk groups.MethodsSerum DNA was extracted from peripheral blood of 70 ESCC patients and 30 controls of benign esophageal diseases or healthy donors. Promoter methylation status of RUNX3 gene was determined by methylation-specific polymerase chain reaction (MSP), and the correlation between methylation profiles and clinicopathological parameters was statistically analyzed.ResultsAberrant methylation of RUNX3 gene was detected in 36 of 70 (51.4%) ESCC patients, the frequency was significantly higher than that in benign esophgeal disease (2/20,10%) and healthy controls (0/10) (P<0.001).RUNX3 hypermethylation status was found to be correlated with advance stage and lymph metastasis in ESCC patients.ConclutionsFrequent hypermethylation of RUNX3 promoter exists in ESCC, suggesting it may be a promising biomarker for the early diagnosis and prognosis assessment. |
PDF Full Text Request