Abstract
BACKGROUND: The early detection of digestive cancers and precancerous diseases remains a significant challenge. This study aimed to investigate the performance of the blood methylated SEPT9 (mSEPT9) assay, and the combination of this assay with serum protein markers, in hospital-based opportunistic screening strategies for digestive cancers. METHODS: Opportunistic screening was performed in the participating hospitals on outpatients and inpatients who met specific inclusion criteria. We recruited a total of 2030 subjects, including 764 cancer patients [291 colorectal cancer (CRC), 239 gastric cancer (GC), 106 esophageal cancer (EC), and 128 hepatocellular carcinoma (HCC)], 423 subjects with precancerous diseases, and 843 normal subjects. All samples were transported to an authenticated clinical laboratory where the mSEPT9 tests were performed. RESULTS: When used separately, the mSEPT9 detected CRC, GC, EC, and HCC, with a sensitivity of 76.6% [area under the receiver operating characteristic curve (AUC) = 0.86)], 47.7% (AUC = 0.76), 42.6% (AUC = 0.69), and 76.7% (AUC = 0.85) and a specificity of 94.6%, 92.3%, 92.5%, and 87.7%, respectively. The mSEPT9 assay also had potent ability to discriminate cancer from non-cancer subjects. The combination of mSEPT9 with CEA, CA724, SNCG, or AFP significantly enhanced the sensitivity for CRC, GC, EC, and HCC to 86.4% (AUC = 0.99, specificity = 92.8%), 63.6% (AUC = 0.86, specificity = 91.1%), 71.3% (AUC = 0.81, specificity = 82.1%), and 83.3% (AUC = 0.93, specificity = 85.1%), respectively. The performance of the mSEPT9 assay was influenced by cancer stage, patient age, pathological types, and the location of cancer. We also identified that mSEPT9 was an independent risk factor and was a valuable predictor for the long-term survival of digestive cancer patients, with a hazard ratio of 2.84, 2.07, 1.88, and 2.45, for CRC, GC, EC, and HCC, respectively. CONCLUSION: The blood mSEPT9 assay, whether used alone or in combination with serum protein markers, is effective for the opportunistic screening of digestive cancers. Furthermore, mSEPT9 is an independent risk factor and a predictive marker for the long-term survival of digestive cancer patients.