AUTHOR=Pei Bing , Zhao Guodong , Geng Zhixin , Wang Yue , Wang Menglin , Wang Xiaomei , Xiong Shangmin , Zheng Minxue 

TITLE=Identifying potential DNA methylation markers for the detection of esophageal cancer in plasma

JOURNAL=Frontiers in Genetics

VOLUME=14

YEAR=2023

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2023.1222617

DOI=10.3389/fgene.2023.1222617

ISSN=1664-8021

ABSTRACT=<p><bold>Background:</bold> 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.</p><p><bold>Methods:</bold> 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 (<italic>ELMO1</italic>, <italic>ZNF582</italic>, <italic>FAM19A4</italic>, <italic>PAX1</italic>, <italic>C13orf18</italic>, <italic>JAM3</italic> and <italic>TERT</italic>) 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.</p><p><bold>Results:</bold><italic>ZNF582</italic>, <italic>FAM19A4</italic>, <italic>JAM3</italic>, or <italic>TERT</italic> methylation in plasma was shown to significantly distinguish EC and control subjects (<italic>p</italic> &lt; 0.05), and the combination of <italic>ZNF582</italic> and <italic>FAM19A4</italic> 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%.</p><p><bold>Conclusion:</bold> The identified methylation marker panel provided a potential non-invasive strategy for EC detection, but further validation should be performed in more clinical centers.</p>