Beijing Advanced Innovation Center for Genomics, School of Life Sciences, Department of General Surgery, Third Hospital, Peking University, Beijing, China.
Biomedical Pioneering Innovation Center, Peking University, Beijing, China.
Clin Chem. 2022 Feb 1;68(2):354-364. doi: 10.1093/clinchem/hvab204.
Aberrant DNA hypermethylation of CpG islands (CGIs) occurs frequently and is genome-wide in human gastric cancer (GC). A DNA methylation approach in plasma cell-free DNA (cfDNA) is attractive for the noninvasive detection of GC. Here, we performed genome-scale cfDNA methylation analysis in patients with GC.
We used MCTA-Seq, a genome-scale DNA methylation analysis method, on the plasma samples of patients with GC (n = 89) and control participants (n = 82), as well as 28 pairs of GC and adjacent noncancerous tissues. The capacity of the method for detecting GC and discriminating GC from colorectal cancer (CRC) and hepatocellular carcinoma (HCC) was assessed.
We identified 153 cfDNA methylation biomarkers, including DOCK10, CABIN1, and KCNQ5, for detecting GC in blood. A panel of these biomarkers gave a sensitivity of 44%, 59%, 78%, and 100% for stage I, II, III, and IV tumors, respectively, at a specificity of 92%. CpG island methylation phenotype (CIMP) tumors and NON-CIMP tumors could be distinguished and detected effectively. We also identified several hundreds of cfDNA biomarkers differentially methylated between GC, CRC, and HCC, and showed that MCTA-Seq can discriminate early-stage GC, CRC, and HCC in blood by using a high specificity (approximately 100%) algorithm.
Our comprehensive analyses provided valuable data on cfDNA methylation biomarkers of GC and showed the promise of cfDNA methylation for the blood-based noninvasive detection of GC.
人类胃癌（GC）中 CpG 岛（CGI）的异常 DNA 高甲基化频繁发生且遍布全基因组。血浆无细胞游离 DNA（cfDNA）中的 DNA 甲基化方法对于 GC 的非侵入性检测具有吸引力。在此，我们对 GC 患者进行了全基因组 cfDNA 甲基化分析。
我们使用 MCTA-Seq 对 GC 患者（n=89）和对照参与者（n=82）的血浆样本以及 28 对 GC 和相邻非癌组织进行了全基因组 DNA 甲基化分析。评估了该方法检测 GC 和区分 GC 与结直肠癌（CRC）和肝细胞癌（HCC）的能力。
我们在血液中鉴定出 153 个 cfDNA 甲基化生物标志物，包括 DOCK10、CABIN1 和 KCNQ5，用于检测 GC。这些生物标志物的组合在特异性为 92%的情况下，对 I 期、II 期、III 期和 IV 期肿瘤的敏感性分别为 44%、59%、78%和 100%。CpG 岛甲基化表型（CIMP）肿瘤和 NON-CIMP 肿瘤可以有效区分和检测。我们还鉴定出数百个 cfDNA 生物标志物在 GC、CRC 和 HCC 之间存在差异甲基化，并且表明 MCTA-Seq 可以通过使用高特异性（约 100%）算法在血液中区分早期 GC、CRC 和 HCC。
我们的综合分析提供了 GC 的 cfDNA 甲基化生物标志物的有价值数据，并表明 cfDNA 甲基化在基于血液的 GC 非侵入性检测方面具有广阔的应用前景。
