Abstract
Identifying sensitive and specific biomarkers for early detection of cancer is immensely imperative for early diagnosis and treatment and better clinical outcome of cancer patients. This study aimed to construct a specific DNA methylation pattern of cancer suppressor genes and explore the feasibility of applying cell-free DNA based methylation as a biomarker for early diagnosis of esophageal squamous cell carcinoma (ESCC). We recruited early stage ESCC patients from Yangzhong County, China. The Illumina Infinium 450K Methylation BeadChip was used to construct a genome-wide DNA methylation profile. Then, differentiated genes were selected for the validation study using the Sequenom MassARRAY platform. The frequency of methylation was compared between cancer tissues, matched cell-free DNAs and normal controls. The specific methylation profiles were constructed, and the sensitivity and specificity were calculated. Seven CG sites in three genes CASZ1, CDH13 and ING2 were significantly hypermethylated in ESCC as compared with normal controls. A significant correlation was found between the methylation of DNA extracted from cancer tissues and matched plasma cell-free DNA, either for individual CG site or for cumulative methylation analysis. The sensitivity and specificity reached 100% at an appropriate cut-point using these specific methylation biomarkers. This study revealed that aberrant DNA methylation is a promising biomarker for molecular diagnosis of esophageal cancer. Hypermethylation of CASZ1, CDH13 and ING2 detected in plasma cell-free DNA can be applied as a potential noninvasive biomarker for diagnosis of esophageal cancer.
Highlights
Esophageal cancer is the eighth most common cancer in terms of incidence and ranks sixth in cancer-related deaths worldwide[1–2]
While esophageal adenocarcinoma has markedly increased in developed countries during last few decades, esophageal squamous cell carcinoma (ESCC) still accounts for a large part, especially in Asian countries[3]
This study aimed to compare the consistency of DNA methylation between esophageal cancer tissues and cellfree DNA extracted from the plasma of ESCC patients, construct DNA methylation patterns of cancer suppressor genes and explore the feasibility of applying cellfree DNA based methylation profile as a biomarker for early diagnosis of esophageal cancer
Summary
Esophageal cancer is the eighth most common cancer in terms of incidence and ranks sixth in cancer-related deaths worldwide[1–2]. It usually occurs in the middle or upper one-third of the esophagus as the squamous cell carcinoma, or in the lower one-third or junction of the esophagus and stomach as the adenocarcinoma. In spite of the advances in diagnostic methods and the improvements in surgical techniques and adjuvant chemoradiation therapy, the majority of ESCC are diagnosed at advanced stages with the overall 5-year survival rates of 15%–50%[4–5]. If patients can be diagnosed and treated at an early stage, the 5-year survival rate would reach to 100% after the endoscopic mucosectomy[6]. To identify sensitive and specific biomarkers for the early detection of this disease is immensely imperative for the patient’s prognosis
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