A Novel Plasma-Based Methylation Panel for Upper Gastrointestinal Cancer Early Detection

Background: Upper gastrointestinal cancer (UGC) is an important cause of cancer death in China, with low five-year survival rates due to the majority of UGC patients being diagnosed at an advanced stage. Therefore, there is an urgent need to develop cost-effective, reliable and non-invasive methods for the early detection of UGC.

Methods: A novel plasma-based methylation panel combining simultaneous detection of three methylated biomarkers (, and ) and an internal control gene were developed and used to examine plasma samples from 186 UGC patients and 190 control subjects.

Results: The results indicated excellent PCR amplification efficiency and reproducibility of , and in the range of 10-100,000 copies per PCR reaction of fully methylated genomic DNA. The methylation levels of , and were significantly higher in UGC samples than those in control subjects. The sensitivities of , and alone for UGC detection were 32.3%, 61.3% and 30.6%, respectively; when three markers were combined, the sensitivity was improved to 71.0%, with a specificity of 90.0%, and the area under the curve (AUC) was 0.870 (95% CI: 0.832-0.902).

Conclusion: Methylated , and were specific for UGC and the three-methylated gene panel provided an alternative non-invasive choice for UGC early detection.