Opportunistic screening and survival prediction of digestive cancers by the combination of blood mSEPT9 with protein markers

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.

An Inflammatory Response-Related Gene Signature Can Impact the Immune Status and Predict the Prognosis of Hepatocellular Carcinoma

“…For example, it can distinguish immune checkpoints genes and tumor drug resistance genes to a high-expression group and a low-expression group, and risk score has been proved to be correlated with many chemotherapeutic drugs resistance. A recent study pointed out that mSEPT9 as a prognostic marker of HCC has remarkable predictive effect for prognosis in HCC (AUC = 0.85) ( 26 ). The methylation level of SEPT9 gene was detected by methylation specific PCR (MS-PCR).…”

Methylated Septin9 (mSEPT9): A Promising Blood-Based Biomarker for the Detection and Screening of Early-Onset Colorectal Cancer

“…It is possible that mSEPT will perform even better in optimal clinical screening settings. Furthermore, we were able to quantitatively measure mSEPT in non-colorectal cancer cell lines, suggesting that mSEPT may have applicability as a biomarker in other cancer types, recent data suggests this to be the case for esophageal, gastric, and liver cancer (51,52). Future studies could focus on a pan-cancer evaluation of mSEPT combined with organ-specific markers to distinguish the biomarker origin.…”

Plasma Methylated RNF180 for Noninvasive Diagnosis of Gastric Cancer

“…Although the sensitivity was higher than that previously reported, the specificity was relatively lower. This was because our study was conducted under the background of opportunistic screening, which was different from screening an average-risk population; the probability of GC detection by opportunistic screening is higher [ 24 ], i.e., the false positive rate of BGD is higher than that of healthy controls. Besides, the mRNF180-positive rate in GU was 60.00% compared to 71.67% in GC, which was much higher than the positive rate in CSG and CAG.…”