Diagnostic Value of Methylated Septin9 for Colorectal Cancer Detection

Abstract

BackgroundMethylated Septin9 (mSEPT9) has been suggested as a reliable biomarker in colorectal cancer (CRC) detection. We aimed to determine the diagnostic value of mSEPT9 for CRC detection in Chinese patients. In addition, we compared the diagnostic efficacy of mSEPT9 to traditional screening method [fecal occult blood test (FOBT)] and two biomarkers [carcinoembryonic antigen (CEA) and carbohydrate antigen-199 (Ca-199)].MethodsOverall 248 subjects including 123 patients with CRC and 125 controls were included. Plasma and fecal samples were collected for CEA, Ca-199, mSEPT9, and FOBT tests. Sensitivity and specificity were calculated to evaluate the diagnostic efficacy of each method; receiver operating characteristic (ROC) curve was plotted for the assessment of diagnostic accuracy, and comparisons among FOBT, mSEPT9, and the combination were assessed through area under the ROC curve (AUC).ResultsmSEPT9 achieved overall sensitivity and specificity of 61.8% [95% confidence interval (CI): 53.0–69.9%] and 89.6% (83.0–93.8%), respectively, with an AUC value of 0.757 (95% CI: 0.701–0.807), superior to FOBT [sensitivity: 61.4% (50.9–70.9%); specificity: 70.3% (59.1–79.5%); AUC: 0.658 (0.578–0.723)], CEA [sensitivity: 35.0% (27.1–43.7%); specificity: 62.6% (53.8–70.7%); AUC: 0.485 (0.411–0.559)], and Ca-199 [sensitivity: 17.9% (12.1–25.6%); specificity: 55.7% (48.9–64.1%); AUC: 0.353 (0.283–0.423)]. The combination of mSEPT9 and FOBT further improved sensitivity and AUC value of 84.1% (75.1–90.3%) and 0.807 (0.752–0.863), respectively, while specificity was declined to 62.2% (50.8–72.4%).ConclusionmSEPT9 demonstrated best diagnostic ability in CRC detection compared with FOBT, CEA, and Ca-199. The combination of mSEPT9 and FOBT further improved diagnostic sensitivity especially for early stage disease, which may provide a new approach for future CRC screening, though further investigations are warranted.

Methylated Septin 9 and Carcinoembryonic Antigen for Serological Diagnosis and Monitoring of Patients with Colorectal Cancer After Surgery

“…reported similar results, with respective sensitivities of 95.6% (88/92) and 51.8%(14/27), and specificities of 84.8% and 85.2% for mSEPT9 and CEA 20 . In another recent study, mSEPT9 was also shown to have higher diagnostic value than CEA for both sensitivity (61.8% vs 35.0%) and specificity (89.6% vs 62.6%) 22 . The sensitivity of plasma mSEPT9 for detecting CRC was highly tumor stage-dependent.…”

The role of mSEPT9 in screening, diagnosis, and recurrence monitoring of colorectal cancer

“…They also found that CRCs with higher histological grade showed a higher positive rate of m SEPT9 [34]. Previous study by Xie et al showed that m SEPT9 had higher sensitivity for patients with distant metastasis [35]. Methylation levels of SEPT9 were significantly associated with nodal (N), tumor (T) and metastasis (M) categories, as well as Dukes category, which indicated that peripheral m SEPT9 in plasma could be a powerful auxiliary molecular staging parameter, and together with TNM classification, facilitate molecular disease staging of CRC.…”

Trends in and Predictions of Colorectal Cancer Incidence and Mortality in China From 1990 to 2025

“…For example, more sigmoidoscopy screening would identify more rectal cases than colonoscopy does, though these screening methods have not widely adopted in China due to their cost and availability. In addition, screening methods with improved diagnostic ability or more sensitive biomarkers, such as methylated Septin9 (m SEPT9 ), have been proposed and developed (54), though these potential biomarkers might be expensive and also not recommended by the current global guidelines or Asian-pacific guidelines for CRC screening.…”