Diagnostic Accuracy of Methylated SEPT9 for Blood-based Colorectal Cancer Detection: A Systematic Review and Meta-Analysis

Abstract

Objectives:More convenient and effective blood-based methods are believed to increase colorectal cancer (CRC) detection adoption. The effectiveness of methylated SPET9 for CRC detection has been reviewed in the newly published recommendation statement by US Preventive Services Task Force (USPSTF), while detailed instructions were not provided, which may be a result of insufficient evidence. Therefore, more evidence is needed to assist practitioners to thoroughly understand the utilization of this special maker.Methods:Based on the standard method, a systematic review and meta-analysis was performed. Quadas-2 was used to assess the methodological quality of studies. Relevant studies were searched and screened from PubMed, Embase and other literature databases up to June 1, 2016. Pooled sensitivity, specificity and diagnostic odds ratio were summarized by bivariate mixed effect model and area under the curve (AUC) was estimated by hierarchical summary receiver operator characteristic curve.Results:25 studies were included for analysis. The pooled sensitivity, specificity and AUC were 0.71, 0.92 and 0.88, respectively. Among the various methods and assays, Epipro Colon 2.0 with 2/3 algorithm was the most effective in colorectal cancer detection. Positive ratio of mSEPT9 was higher in advanced CRC (45% in I, 70% in II, 76% in III, 79% in IV) and lower differentiation (31% in high, 73% in moderate, 90% in low) tissue. However, this marker has poor ability of identifying precancerous lesions according to current evidence.Conclusions:mSEPT9 is a reliable blood-based marker in CRC detection, particularly advanced CRC. Epipro Colon 2.0 with 2/3 algorithm is currently the optimal method and assay to detect CRC.

Plasma miRNA‐based signatures in CRC screening programs

“…Stool‐based assays like the FIT are less invasive but have limited ability to detect premalignant colorectal adenomas. Recently, tumor‐derived cell‐free nucleic acids released in stool and blood have emerged as promising biomarkers in cancer, and tests for the detection of cell‐free nucleic acids such as the stool‐based DNA multimarker (ColoGuard®), or the blood‐based test for detection of methylated Septin 9 DNA have been developed . However, a major proportion of early stage tumors does not release detectable amounts of circulating tumor DNA, even when extremely sensitive techniques are used for their identification …”

Evaluation of a novel liquid biopsy-based ColoScape assay for mutational analysis of colorectal neoplasia and triage of FIT+ patients: a pilot study

“…An article published by Imperiale et al in the NEJM in 201414 described an FDA-approved stool-DNA test (Cologuard, Exact Sciences, Madison, Wisconsin, USA) and reported sensitivity of 42% for advanced adenomas and 92% for cancer, with a specificity of 87%. Other work has been done employing Septin 9 (Epigenomics), another FDA-approved test based on detection of methylation markers in blood samples 15. DiaCarta Inc., a molecular diagnostic based in Richmond (California), has developed a highly sensitive multiplex real-time qPCR assay that combines a multiplex colorectal gene specific panel7 8 with proprietary xeno nucleic acid (XNA) wild-type clamping probe technology.…”

Screening for Colorectal Cancer Based on the Promoter Methylation Status of the Septin 9 Gene in Plasma Cell Free DNA

“…Test performance (Table 1) was evaluated in a number of case control studies in Europe and China [27,[31][32][33][34]. As outlined in these studies, test sensitivity was reported to range from 73-81% and test specificity was reported to range from 96-99%.…”

“…A development project was undertaken to reduce the research observations to practice requiring standardization of each protocol step. The test was developed and optimized through different versions as outlined (Table 1) and the performance characteristics have been summarized in a meta-analysis including 25 studies [27]. …”