The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Suzhou, Jiangsu 215000, China.
ZJUT Yinhu Research Institute of Innovation and Entrepreneurship Fuyang District, Hangzhou, Zhejiang 311400, China; Zhejiang University Kunshan Biotechnology Laboratory, Zhejiang University Kunshan Innovation Institute, Kunshan, Jiangsu 215300, China; Suzhou VersaBio Technologies Co. Ltd., Kunshan, Jiangsu 215300, China.
Gene. 2024 May 15;906:148261. doi: 10.1016/j.gene.2024.148261. Epub 2024 Feb 9.
DNA methylation is highly correlated with cancer and embryo development, and plasma-based methylation markers have been widely used for cancer early detection. However, whether the commonly used cancer methylation markers cause "false positives" in the plasma of pregnant women has not been comprehensively evaluated.
We conducted a case-control study from February 2021 to March 2023, which included 138 pregnant women and 44 control women. Plasma cell-free DNA (cfDNA) was isolated and bisulfite-converted, and then the methylation levels of eight methylated markers related to gastrointestinal cancer (SEPT9, SDC2, C9orf50, KCNQ5, CLIP4, TFPI2, ELMO1 and ZNF582) and three markers related to lung cancer (SHOX2, RASSF1A and PTGER4) were analyzed.
When comparing the plasma of pregnant women to that of control women, SEPT9, CLIP4, ZNF582, SHOX2, RASSF1A and PTGER showed significantly higher levels of methylation (p < 0.05). These positive signals originate from the placenta/fetus rather than the mother. We found no discernible difference in DNA methylation levels between fetal cfDNA fractions of < 10 % and ≥ 10 % in pregnant women (p > 0.05), while CLIP4 and PTGER4 showed high methylation levels in the assisted fertilization group compared to the natural fertilization group (p < 0.05).
Our study shows that cancer and fetus/placenta exhibit similar DNA methylation patterns, and some gastrointestinal cancer and lung cancer-related methylation markers also show positives in maternal plasma. This is an important consideration in the design and application of plasma-based cancer liquid biopsy assays.
DNA 甲基化与癌症和胚胎发育高度相关，基于血浆的甲基化标志物已广泛用于癌症早期检测。然而，常用的癌症甲基化标志物是否会在孕妇的血浆中导致“假阳性”尚未得到全面评估。
我们进行了一项病例对照研究，时间为 2021 年 2 月至 2023 年 3 月，共纳入 138 名孕妇和 44 名对照女性。分离并亚硫酸氢盐转化血浆无细胞游离 DNA（cfDNA），然后分析与胃肠道癌症相关的 8 个甲基化标志物（SEPT9、SDC2、C9orf50、KCNQ5、CLIP4、TFPI2、ELMO1 和 ZNF582）和与肺癌相关的 3 个标志物（SHOX2、RASSF1A 和 PTGER4）的甲基化水平。
与对照女性相比，孕妇血浆中 SEPT9、CLIP4、ZNF582、SHOX2、RASSF1A 和 PTGER 的甲基化水平明显升高（p<0.05）。这些阳性信号源自胎盘/胎儿，而非母亲。我们未发现孕妇 cfDNA 中胎儿成分<10%和≥10%之间的 DNA 甲基化水平有明显差异（p>0.05），而 CLIP4 和 PTGER4 在辅助生殖组中的甲基化水平高于自然生殖组（p<0.05）。
本研究表明，癌症和胎儿/胎盘表现出相似的 DNA 甲基化模式，一些与胃肠道癌症和肺癌相关的甲基化标志物在母体血浆中也呈现阳性。这是设计和应用基于血浆的癌症液体活检检测时需要考虑的重要因素。
Zotero 插件