A pooled analysis of the diagnostic efficacy of plasmic methylated septin-9 as a novel biomarker for colorectal cancer

Abstract

Abstract. The methylation status of septin-9 gene in plasma has been developed as a promising biomarker to aid in the diagnosis of colorectal cancer (CRC). In this study, we aimed to evaluate the overall diagnostic ability of septin-9 methylation for detection of CRC. Studies on the diagnostic performance of plasma septin-9 in CRC were searched from the online databases up to January 31st, 2017. Risk of bias among the studies was estimated according to the Quality Assessment of Studies of Diagnostic Accuracy included in the Systematic Reviews (QUADAS) II checklist. The aggregation of the effect sizes was enabled by utilizing a bivariate analysis model. A meta-regression test and influence analysis were conducted to determine the underlying sources of heterogeneity. According to the predefined criteria, 1,462 patients with CRC from 14 eligible trials were included. The quantitative meta-analyses showed that methylated septin-9 in plasma sustained a pooled sensitivity of 0.67 (95% CI, 0.61-0.73) and specificity of 0.89 (95% CI, 0.86-0.92) in discriminating CRC patients from cancer-free individuals, along with an area under the curve of 0.87. Moreover, the stratified analyses grouped by ethnicity demonstrated that methylayted septin-9 testing achieved a better sensitivity of 0.72 (95% CI, 0.68-0.76) in the European-based population group and a higher specificity of 0.90 (95% CI, 0.88-0.92) in the Asian-based population group. Plasmic methylated septin-9 suggests a promising diagnostic efficacy in confirming CRC. However, more studies are required to confirm our findings.

Cell-Free Circulating Methylated SEPT9 for Noninvasive Diagnosis and Monitoring of Colorectal Cancer

“…However, clinical compliance of this stool-based test was low because of its inconvenience and requirement of repeated tests [ 27 ]. The sensitivity of plasma mSEPT9 for CRC using 2/3 algorithm in our study is consistent with the data in a quantitative meta-analysis by Zhang et al [ 36 ], which showed that plasma mSEPT9 sustained a pooled sensitivity of 64% (95% CI: 59%–68%) for CRC detection in the Asian-based population. Previous studies showed that the 1/3 algorithm draws higher sensitivity and lower specificity than the 2/3 algorithm in mSEPT9 test, with the sensitivity ranging from 68% (95% CI: 53% -80%) to 95.6% (95% CI: 89.2%–98.8%) for CRC detection [ 6 , 37 – 39 ].…”

Strategies for Colorectal Cancer Screening

“…47 A meta-analysis of studies of this assay found a pooled sensitivity of 67% and specificity of 89% for detection of CRC. 48 Capsule colonoscopy involves ingestion of a large pill-sized camera that records images during its transit through the intestine. Highly effective bowel preparation is required, typically involving use of booster doses and/or a prokinetic agent.…”

Utility of the methylated SEPT9 test for the early detection of colorectal cancer: a systematic review and meta-analysis of diagnostic test accuracy

“…Additionally, four studies included in this meta-analysis were assessed as having a high probability of patient selection bias and could not include research reported since 2017. Two other meta-analyses5 6 did not conduct a comprehensive analysis of diagnostic accuracy of mSEPT9 tests: the first study5 considered covariates to assess sources of heterogeneity but provided limited evidence of the effect of those covariates on the diagnostic efficacy of mSEPT9. The second study6 only provided estimates on sensitivity and specificity.…”