Pei Bing, Zhao Guodong, Geng Zhixin, Wang Yue, Wang Menglin, Wang Xiaomei, Xiong Shangmin, Zheng Minxue
The Suqian Clinical College of Xuzhou Medical University, Suqian, China.
Department of Clinical Laboratory, The Affiliated Suqian First People's Hospital of Nanjing Medical University, Suqian, China.
Front Genet. 2023 Oct 4;14:1222617. doi: 10.3389/fgene.2023.1222617. eCollection 2023.
Esophageal cancer (EC) is a leading cause of cancer-related deaths in China, with the 5-year survival rate reaching less than 30%, because most cases were diagnosed and treated at the advanced stage. However, there is still a lack of low-cost, efficient, and accurate non-invasive methods for the early detection of EC at present. A total of 48 EC plasma and 101 control plasma samples were collected in a training cohort from 1 January 2021 to 31 December 2021, and seven cancer-related DNA methylation markers (, , , , , and ) were tested in these samples to select potential markers. In total, 20 EC, 10 gastric cancer (GC), 10 colorectal cancer (CRC), and 20 control plasma samples were collected in a validation cohort to evaluate the two-gene panel. , , , or methylation in plasma was shown to significantly distinguish EC and control subjects ( < 0.05), and the combination of and methylation was the two-gene panel that exhibited the best performance for the detection of EC with 60.4% sensitivity (95% CI: 45.3%-73.9%) and 83.2% specificity (95% CI: 74.1%-89.6%) in the training cohort. The performance of this two-gene panel showed no significant difference between different age and gender groups. When the two-gene panel was combined with CEA, the sensitivity for EC detection was further improved to 71.1%. In the validation cohort, the sensitivity of the two-gene panel for detecting EC, GC, and CRC was 60.0%, 30.0%, and 30.0%, respectively, with a specificity of 90.0%. The identified methylation marker panel provided a potential non-invasive strategy for EC detection, but further validation should be performed in more clinical centers.
食管癌（EC）是中国癌症相关死亡的主要原因之一，5年生存率不到30%，因为大多数病例在晚期才被诊断和治疗。然而，目前仍缺乏低成本、高效且准确的非侵入性方法用于食管癌的早期检测。在2021年1月1日至2021年12月31日的一个训练队列中，共收集了48份食管癌血浆样本和101份对照血浆样本，并对这些样本检测了7种与癌症相关的DNA甲基化标志物（、、、、、和）以筛选潜在标志物。在一个验证队列中，总共收集了20份食管癌、10份胃癌（GC）、10份结直肠癌（CRC）和20份对照血浆样本以评估双基因组合。血浆中、、、或甲基化显示能显著区分食管癌患者和对照受试者（<0.05），且和甲基化的组合是在训练队列中对食管癌检测表现最佳的双基因组合，灵敏度为60.4%（95%CI：45.3%-73.9%），特异性为83.2%（95%CI：74.1%-89.6%）。该双基因组合在不同年龄和性别组之间的表现无显著差异。当双基因组合与癌胚抗原（CEA）联合使用时，食管癌检测的灵敏度进一步提高到71.1%。在验证队列中，双基因组合检测食管癌、胃癌和结直肠癌的灵敏度分别为60.0%、30.0%和30.0%，特异性为90.0%。所确定的甲基化标志物组合为食管癌检测提供了一种潜在的非侵入性策略，但应在更多临床中心进行进一步验证。
