Tang Dong, Liu Jun, Wang Dao-rong, Yu Hai-feng, Li Yong-kun, Zhang Jing-qiu
Department of Gastrointestinal Surgery, the First Affiliated Hospital of Yangzhou University, Yangzhou, China.
Clin Invest Med. 2011 Apr 1;34(2):E88-95. doi: 10.25011/cim.v34i1.15105.
The aim of this study was to investigate the diagnostic and prognostic significance of the methylation status of secreted frizzled-related protein 2 (SFRP2) in colorectal cancer (CRC).
Methylation-specific PCR assay was performed to analyze SFRP2 promoter methylation in solid tissue, stool and serum samples collected from 169 CRC patients, 63 patients with advanced adenomas, 46 patients with non-adenomatous polyps and 30 normal healthy controls.
Methylated SFRP2 was frequently detected in CRC tissues and precancerous lesions. The sensitivity of SFRP2 methylation levels in tissue, fecal and serum DNA for the detection of CRC was similar, ranging from 66.9 to 88.2%; however, serum SFRP2 methylation levels showed a markedly higher specificity in discriminating CRCs from benign adenomas than those of SFRP2 methylation levels in tumor and fecal DNA. Moreover, serum SFRP2 methylation was significantly associated with poor differentiation grade (P=0.019), serosal/subserosal invasion (P < 0.001), lymph node metastasis status (P < 0.001) and TNM stage (P < 0.001) of CRC. CRC patients with SFRP2 hypermethylation in tumor, stool and serum samples had a significantly shorter overall survival than those negative for SFRP2 methylation (P=0.0216, 0.0219, and 0.0255, respectively). Multivariate Cox regression analysis revealed that SFRP2 promoter methylation in tumor samples was an independent prognostic factor for overall survival.
Our data suggest that serum SFRP2 methylation status represents a promising, non-invasive marker for CRC detection and staging. Hypermethylated SFRP2 may have prognostic relevance in patients with CRC.
本研究旨在探讨分泌型卷曲相关蛋白2（SFRP2）甲基化状态在结直肠癌（CRC）中的诊断及预后意义。
采用甲基化特异性PCR检测法，对169例CRC患者、63例晚期腺瘤患者、46例非腺瘤性息肉患者及30例正常健康对照者的实体组织、粪便及血清样本中的SFRP2启动子甲基化情况进行分析。
CRC组织及癌前病变中常检测到SFRP2甲基化。组织、粪便及血清DNA中SFRP2甲基化水平对CRC检测的敏感性相似，范围为66.9%至88.2%；然而，血清SFRP2甲基化水平在鉴别CRC与良性腺瘤方面的特异性显著高于肿瘤及粪便DNA中的SFRP2甲基化水平。此外，血清SFRP2甲基化与CRC的低分化程度（P=0.019）、浆膜/浆膜下侵犯（P<0.001）、淋巴结转移状态（P<0.001）及TNM分期（P<0.001）显著相关。肿瘤、粪便及血清样本中SFRP2高甲基化的CRC患者的总生存期显著短于SFRP2甲基化阴性的患者（分别为P=0.0216、0.0219和0.0255）。多因素Cox回归分析显示，肿瘤样本中SFRP2启动子甲基化是总生存期的独立预后因素。
我们的数据表明，血清SFRP2甲基化状态是一种有前景的、用于CRC检测及分期的确非侵入性标志物。SFRP2高甲基化可能与CRC患者的预后相关。
