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

Abstract

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. A novel plasma-based methylation panel combining simultaneous detection of three methylated biomarkers (ELMO1, ZNF582 and TFPI2) and an internal control gene were developed and used to examine plasma samples from 186 UGC patients and 190 control subjects. The results indicated excellent PCR amplification efficiency and reproducibility of ELMO1, ZNF582 and TFPI2 in the range of 10-100,000 copies per PCR reaction of fully methylated genomic DNA. The methylation levels of ELMO1, ZNF582 and TFPI2 were significantly higher in UGC samples than those in control subjects. The sensitivities of ELMO1, ZNF582 and TFPI2 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). Methylated ELMO1, ZNF582 and TFPI2 were specific for UGC and the three-methylated gene panel provided an alternative non-invasive choice for UGC early detection.