The Stool DNA Test Is More Accurate Than the Plasma Septin 9 Test in Detecting Colorectal Neoplasia

Abstract

Background & Aims Several noninvasive tests have been developed for colorectal cancer (CRC) screening. We compared the sensitivities of a multi-marker test for stool DNA (sDNA) and a plasma test for methylated Septin 9 (SEPT9) in identifying patients with large adenomas or CRC. Methods We analyzed paired stool and plasma samples from 30 patients with CRC and 22 with large adenomas from Mayo Clinic archives. Stool (n=46) and plasma (n=49) samples from age- and sex-matched patients with normal colonoscopy results were used as controls. The sDNA test is an assay for methylated BMP3, NDRG4, vimentin, and TFPI2; mutant KRAS; the β-actin gene, and quantity of hemoglobin (by the porphyrin method). It was performed blindly at Exact Sciences (Madison WI); the test for SEPT9 was performed at ARUP Laboratories (Salt Lake City UT). Results were considered positive based on the manufacturer's specificity cutoff values of 90% and 89%, respectively. Results The sDNA test detected adenomas (median 2 cm, range 1–5 cm) with 82% sensitivity (95% confidence interval [CI], 60%–95%); SEPT9 had 14% sensitivity (95% CI, 3%–35%; P=.0001). The sDNA test identified patients with CRC with 87% sensitivity (95% CI, 69%–96%); SEPT9 had 60% sensitivity (95% CI, 41%–77%; P=.046). The sDNA test identified patients with stage I–III CRC with 91% sensitivity (95% CI, 71%–99%); SEPT9 had 50% sensitivity (95% CI, 28%–72%; P=.013); for stage IV CRC, sensitivity values were 75% (95% CI, 35%–97%) and 88% (95% CI, 47%–100%), respectively (P=.56). False-positive rates were 7% for the sDNA test and 27% for SEPT9. Conclusions Based on analyses of paired samples, the sDNA test detects non-metastatic CRC and large adenomas with significantly greater levels of sensitivity than the SEPT9 test. These findings might be used to modify approaches for CRC prevention and early detection.

Advances in epigenetic biomarker research in colorectal cancer

“…Vimentin has a low detection rate in serum, however, and is thus most likely not suitable for use as a serum biomarker for CRC. Recently, Ahlquist et al [26] reported that a panel of methylation markers from stool that includes vimentin has shown a significantly higher sensitivity for CRC, primarily because of higher detection rates in stage Ⅰ-Ⅲ CRC (91% vs 50%).…”

“…Moreover, the methylation of DFNA5 in PB samples from CRC patients was significantly correlated with lymph node metastasis and distant metastasis (P = 0.027) [5] , which suggests that DFNA5 could potentially be an independent prognostic serum biomarker for CRC patients. It is clear, however, that further validation in large-scale prospective trials is necessary before these biomarkers are ready for use in the clinic [26] .…”

“…Bisulfite treatment and methylation specific polymerase chain reaction (PCR) are the two most commonly used techniques. A blood biomarker with a high sensitivity and specificity for CRC can not only be used to segregate high-risk patients for further clinical tests but also be an excellent tool for monitoring CRC recurrence in patients who have undergone tumor resection (Table 1) [20][21][22][23][24][25][26][27][28][29][30] .…”

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

“…Among the methylated genes in CRC, septin-9 has been highlighted as an ideal candidate biomarker (4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19). Septin-9 was initially identified in myeloid neoplasia (20).…”

Laboratory screening markers in gastroenterology - state of the art

“…Rapid advancement of proteomics and associated techniques provides a new promising route for the diagnosis of precancerous laesions 34 . Hypermethylation of the plasma septin-9 gene may be considered as a potential non stool-based screening tool 35,36 . Blood-based biomarkers are not likely to be established as an alternative to FOBT-based CRCA screening, but can be used in combination with iFOBT to increase colorectal screening accuracy [37][38][39] .…”