Department of Internal Medicine, Division of Gastrointestinal, Faculty of Medicine, Ardabil University of Medical Sciences, Ardabil, Iran.
Department of Biology, Faculty of Sciences, Arak University, Arak, Iran.
J Cancer Res Ther. 2023 Oct 1;19(7):1797-1802. doi: 10.4103/jcrt.jcrt_2188_21. Epub 2022 Apr 29.
Colorectal cancer (CRC) has been described as a "silent disease," which can be readily treated in most patients when discovered in its early stages. Considering the limitations of the current conventional tests for the diagnosis of CRC, researchers strive to find noninvasive and more valid biomarkers for the early detection of CRC. It has been shown that tumor-specific methylation patterns can also be identified in peripheral blood mononuclear cells (PBMCs) and are reliable sources of methylation analysis for CRC screening.
We carried out a quantitative methylation analysis on matrix metallopeptidase 9 (MMP9) promoter using methylation quantification endonuclease-resistant DNA (MethyQESD) method. A total of 70 patients with CRC and 70 normal controls were enrolled in this study for methylation analysis in the PBMCs.
Our findings discovered a considerable hypermethylation of MMP9 promoter in CRC patients compared with healthy controls (mean: 47.30% and 20.31%, respectively; P > 0.001). The sensitivity and specificity of the MMP9 gene for the diagnosis of CRC were 88% and 78%, respectively. In addition, on the basis of area under the curve values, the diagnostic power of the MMP9 gene was 0.976 (P < 0.001). Moreover, our analysis established that MMP9 methylation was significantly different between the different stages of CRC (P: 0.034).
Our results showed that MMP9 promoter methylation in PBMCs can be used as an outstanding biomarker for CRC diagnosis. Besides, we confirmed that PBMCs are reliable sources of methylation analysis for CRC screening and MethyQESD is an accurate and fast method for quantitative methylation analyses.
结直肠癌（CRC）被描述为一种“沉默的疾病”，当在早期发现时，大多数患者都可以得到很好的治疗。考虑到目前用于 CRC 诊断的常规检测方法存在局限性，研究人员努力寻找非侵入性和更有效的生物标志物，以实现 CRC 的早期检测。已经表明，外周血单个核细胞（PBMC）中也可以识别肿瘤特异性的甲基化模式，并且是 CRC 筛查中甲基化分析的可靠来源。
我们使用甲基化定量内切酶抗性 DNA（MethyQESD）方法对基质金属蛋白酶 9（MMP9）启动子进行了定量甲基化分析。本研究共纳入 70 例 CRC 患者和 70 例正常对照者进行 PBMC 甲基化分析。
与健康对照组相比，CRC 患者 MMP9 启动子存在明显的高甲基化（平均值分别为 47.30%和 20.31%；P>0.001）。MMP9 基因诊断 CRC 的敏感性和特异性分别为 88%和 78%。此外，根据曲线下面积值，MMP9 基因的诊断能力为 0.976（P<0.001）。此外，我们的分析表明 MMP9 甲基化在 CRC 的不同阶段之间存在显著差异（P：0.034）。
我们的结果表明，PBMC 中 MMP9 启动子甲基化可用作 CRC 诊断的优秀生物标志物。此外，我们证实 PBMC 是 CRC 筛查中甲基化分析的可靠来源，MethyQESD 是一种用于定量甲基化分析的准确、快速方法。
