Background: Esophageal cancer (EC) is the second most common malignant tumor of the digestive system. There is currently no effective noninvasive method for early detection of EC. Methods: We performed a prospective cohort study involving 188 EC patients, 125 patients with benign esophageal diseases, and 270 normal subjects to examine the performance of methylated SEPT9 (mSEPT9) and synuclein gamma (SNCG) individually and in combination. Results: The sensitivity of mSEPT9 and SNCG for EC was 43.1% (AUC = 0.69) at 95.6% specificity and 41.8% (AUC = 0.79) at 92.6% specificity, respectively. The combined detection increased the sensitivity to 71.8% at 90.3% specificity. The combined detection sensitivity for stage I-IV EC was 66.7%, 58.3%, 75.0%, and 88.2%, respectively. No significant difference in combined sensitivity was found among patients with EC of the upper, middle, and lower esophagus, and no significant difference in sensitivity was found between adenocarcinoma and squamous carcinoma. The sensitivity of highly differentiated EC was found to be higher than that of moderately and poorly differentiated EC with SNCG and combined detection. The sensitivity of SNCG in female patients was significantly higher than that in male patients, leading to the same trend in combined detection. Patients aged 40-49 years showed higher combined sensitivity. The sensitivity of SNCG was much higher than that of existing protein markers for digestive cancers. Furthermore, mSEPT9 was capable of predicting the long-term survival of EC patients with a hazard ratio of 2.65. Conclusion: The combined sensitivity of mSEPT7 and SNGG provided significant improvement over any single biomarker for the early detection of EC. mSEPT7 may be useful as a prognostic marker for long-term survival.
Keywords: SEPT9; SNCG; esophageal cancer; methylation; septin9.