结直肠癌患者术前术后粪便DNA中syndecan-2甲基化的对比检测
Comparative detection of syndecan-2 methylation in preoperative and postoperative stool DNA in patients with colorectal cancer.
发表日期:2023 Sep 27
作者:
Ji Hyeong Song, Tae Jeong Oh, Sungwhan An, Kyung Ha Lee, Ji Yeon Kim, Jin Soo Kim
来源:
Epigenetics & Chromatin
摘要:
结直肠癌 (CRC) 的早期检测对于降低癌症相关发病率和死亡率至关重要。粪便 DNA (sDNA) 检测是一种用于早期 CRC 检测的新兴方法。 Syndecan-2 (SDC2) 甲基化是 sDNA 测试的潜在生物标志物。异常的 DNA 甲基化是肿瘤发生过程中的早期表观遗传事件,并且可能在衰老过程中发生在正常结肠粘膜中,这可能会影响 sDNA 检测结果。为了确定 sDNA 中的甲基化 SDC2 在 CRC 手术切除后是否正常化。在这项前瞻性研究中,我们招募了2016年9月至2020年5月期间接受根治性手术切除的151名CRC患者。收集了123名患者的术前粪便样本,收集了122名患者的术后样本。术前和术后患者总共收集了 104 份样本。使用线性靶标富集定量甲基化特异性实时聚合酶链式反应评估 sDNA 中 SDC2 的异常启动子甲基化。利用SDC2甲基化结果分析临床病理参数。术前和术后粪便样本中SDC2甲基化检出率分别为88.6%和19.7%。肿瘤体积大(3 cm,P = 0.019)和T分期晚期(T3-T4,P = 0.033)与术前SDC2甲基化检出率呈正相关。女性与手术后假阳性相关(P = 0.030)。术后循环阈值(CT)较术前显着降低(P < 0.001)。术前甲基化SDC2术后转阴率为79.3%(73/92)。我们的结果表明sDNA的SDC2甲基化检测具有可接受的敏感性和特异性。然而,小尺寸和早期 T 期肿瘤与 SDC2 甲基化检出率较低相关。由于手术后循环阈值显着降低,sDNA的SDC2甲基化检测可能对CRC具有诊断价值。©作者2023。百事登出版集团有限公司出版。保留所有权利。
Early detection of colorectal cancer (CRC) is essential to reduce cancer-related morbidity and mortality. Stool DNA (sDNA) testing is an emerging method for early CRC detection. Syndecan-2 (SDC2) methylation is a potential biomarker for the sDNA testing. Aberrant DNA methylation is an early epigenetic event during tumorigenesis and can occur in the normal colonic mucosa during aging, which can compromise the sDNA test results.To determine whether methylated SDC2 in sDNA normalizes after surgical resection of CRC.In this prospective study, we enrolled 151 patients with CRC who underwent curative surgical resection between September 2016 and May 2020. Preoperative stool samples were collected from 123 patients and postoperative samples were collected from 122 patients. A total of 104 samples were collected from both preoperative and postoperative patients. Aberrant promoter methylation of SDC2 in sDNA was assessed using linear target enrichment quantitative methylation-specific real-time polymerase chain reaction. Clinicopathological parameters were analyzed using the results of SDC2 methylation.Detection rates of SDC2 methylation in the preoperative and postoperative stool samples were 88.6% and 19.7%, respectively. Large tumor size (3 cm, P = 0.019) and advanced T stage (T3-T4, P = 0.033) were positively associated with the detection rate of SDC2 methylation before surgery. Female sex was associated with false positives after surgery (P = 0.030). Cycle threshold (CT) values were significantly decreased postoperatively compared with preoperative values (P < 0.001). The postoperative negative conversion rate for preoperatively methylated SDC2 was 79.3% (73/92).Our results suggested that the SDC2 methylation test for sDNA has acceptable sensitivity and specificity. However, small size and early T stage tumors are associated with a low detection rate of SDC2 methylation. As the cycle threshold values significantly decreased after surgery, SDC2 methylation test for sDNA might have a diagnostic value for CRC.©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.