Rong Jiesheng, Pu Rui, Sun Hongru, Liu Yupeng, Tian Tian, Bi Haoran, Xia Tingting, Zhang Lei, Zhang Yuanyuan, Zhao Yashuang, Zhu Lin
Second Department of Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, People's Republic of China.
Department of Epidemiology, Public Health College, Harbin Medical University, Harbin, Heilongjiang, People's Republic of China.
Gene. 2023 Jun 5;868:147357. doi: 10.1016/j.gene.2023.147357. Epub 2023 Mar 11.
Aberrant promoter methylation of CpG islands plays an important role in carcinogenesis. However, the association between the DNA methylation of JAK-STAT pathway-related genes in peripheral blood leukocytes and colorectal cancer (CRC) susceptibility remains unclear.
We conducted a case-control study of 403 patients with CRC and 419 cancer free controls, and the DNA methylation levels of JAK2, STAT1, STAT3, and SOCS3 in peripheral blood samples from all subjects were assessed using a methylation-sensitive high-resolution melting (MS-HRM) analysis.
Compared with controls, the methylation of the JAK2, STAT1 and SOCS3 genes increased the CRC risk (OR=1.96, 95% CI, 1.12-3.41, P=0.01; OR=5.37, 95% CI, 3.74-7.71, P<0.01; OR=3.30, 95% CI, 1.58-6.87, P<0.01). In the multiple CpG site methylation (MCSM) analysis, a high MCSM value denoted an increased CRC risk (OR=4.97, 95% CI, 3.34-7.37, P<0.01).
In peripheral blood, the methylation of JAK2, STAT1, and high levels of MCSM are promising biomarkers for CRC risk.
CpG岛的异常启动子甲基化在致癌过程中起重要作用。然而，外周血白细胞中JAK-STAT通路相关基因的DNA甲基化与结直肠癌（CRC）易感性之间的关联仍不清楚。
我们对403例CRC患者和419例无癌对照进行了病例对照研究，并使用甲基化敏感高分辨率熔解（MS-HRM）分析评估了所有受试者外周血样本中JAK2、STAT1、STAT3和SOCS3的DNA甲基化水平。
与对照组相比，JAK2、STAT1和SOCS3基因的甲基化增加了CRC风险（OR=1.96，95%CI，1.12-3.41，P=0.01；OR=5.37，95%CI，3.74-7.71，P<0.01；OR=3.30，95%CI，1.58-6.87，P<0.01）。在多CpG位点甲基化（MCSM）分析中，高MCSM值表示CRC风险增加（OR=4.97，95%CI，3.34-7.37，P<0.01）。
在外周血中，JAK2、STAT1的甲基化以及高水平的MCSM是CRC风险的有前景的生物标志物。
