Circulating SFRP 1 promoter methylation status in gastric adenocarcinoma and esophageal squamous cell carcinoma

The secreted frizzled-related protein 1 (SFRP1) gene plays an important role in carcinogenesis of digestive system cancer. Previous studies proved that circulating DNA promoter methylation may be a suitable biomarker for cancer patients. The aim of the present study was to investigate whether the promoter methylation status of serum SFRP1 is a potential biomarker for gastric adenocarcinoma (GAC) and esophageal squamous cell carcinoma (ESCC). The blood samples obtained from 42 GAC and 36 ESCC patients were detected for the promoter methylation status of SFRP1 by methylation‐specific polymerase chain reaction. The control group included 42 benign gastrointestinal disease volunteers (24 benign gastric disease and 18 benign esophageal disease) and 20 healthy volunteers. Serum SFRP1 methylation was evident in 30.95% (13/42) GAC patients and 38.89% (14/36) ESCC patients, which is clearly higher compared to 8.33% (2/24) in benign gastric disease, 11.11% (2/18) in benign esophageal disease and 5% (1/20) in healthy volunteers (P<0.05). The association between the serum SFRP1 promoter methylation status and the clinical pathological features were further analyzed and methylation of the SFRP1 gene was significantly associated with age >60 years in GAC patients (P=0.027). However, no correlations between the SFRP1 methylation status and other clinicopathological parameters were found. In conclusion, the SFRP1 promoter was detected frequently in the serum of GAC and ESCC patients. The detection of circulating methylated SFRP1 in the serum may be a useful biomarker for upper gastrointestinal cancer patients. Introduction Gastric adenocarcinoma (GAC) and esophageal squamous cell carcinoma (ESCC) are two major causes of cancer-related fatalities in China. Although gastroscopy is considered the most sensitive screening tool for upper gastrointestinal cancers, it remains limited in attributing to its potential risk, high cost and intolerance of the invasive procedure in patients (1). Therefore, reliable noninvasive tests for screening and diagnostic purposes are required. Accumulating evidence indicates that carcinogenesis is regulated and controlled not only by genetic but also by epigenetic changes (2,3). There is a marked acceleration observed in the past decade validating the concept that cancer is a disease of epigenetic alterations that are leading candidates for the development of specific markers for cancer detection, diagnosis and prognosis (4). As the most common molecular epigenetic change in human cancer, DNA methylation was proved to silence the tumor suppressor genes in GAC (5,6) and ESCC (7). Due to the relatively significant circulating DNA quantity in peripheral blood, analyses of methylation in serum DNA can potentially serve as an excellent tumor marker for diagnosis and prognosis of cancer (8). The secreted frizzled-related protein 1 (SFRP1) gene belongs to the family of five secreted glycoproteins that have been identified as modulators of the Wnt signaling pathway involved in the development of cancer (9). Previous studies have shown that SFRP1 is downregulated by promoter methylation in numerous types of digestive system cancer, which makes it a candidate for tumor gene suppression (10-12). The present study attempted to identify the SFRP1 promoter methylation status in serum from patients with GAC and ESCC by methylation‐specific polymerase chain reaction (MSPCR), compared to benign gastrointestinal disease and healthy volunteers. The correlation between serum SFRP1 gene promoter methylation and patient clinical pathological parameters were also analyzed to further evaluate the clinical significance of this epigenetic molecular change. Materials and methods Study population. All the samples from human subjects were collected following the approval of the study by the Ethical Circulating SFRP1 promoter methylation status in gastric adenocarcinoma and esophageal squamous cell carcinoma CHANG LIu*, NAN LI*, HENG Lu, ZHENGkAI WANG, CHuNyAN CHEN, LIN Wu, JIONG LIu, yOukE Lu and FANGyu WANG Department of Gastroenterology and Hepatology, Jinling Hospital, School of Medicine, Southern Medical university, Nanjing, Jiangsu 210002, P.R. China Received October 25, 2014; Accepted November 11, 2014 DOI: 10.3892/br.2014. 388 Correspondence to: Professor Fangyu Wang, Department of Gastroenterology and Hepatology, Jinling Hospital, School of Medicine, Southern Medical university, 305 East Zhongshan Road, Nanjing, Jiangsu 210002, P.R. China E-mail: wangfangyu1965@163.com *Contributed equally