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A Stool DNA–Based SDC2 Methylation Test for the Early Detection of Colorectal Cancer in an Asymptomatic, High-Risk Population
TAKE-HOME MESSAGE
- This multicenter, prospective study evaluated the clinical performance of a stool DNA–based Syndecan 2 (SDC2) methylation test for detecting colorectal cancer (CRC) in asymptomatic or high-risk CRC populations. Adults (N = 1124) scheduled for screening colonoscopy across eight clinical sites in South Korea were enrolled. The stool SDC2 methylation test had a sensitivity and specificity of 95.0% and 81.5%, respectively, for detecting CRC with an overall accuracy of 81.8%.
- This study suggests that the stool DNA–based SDC2 methylation test has a high sensitivity for detecting CRC in an asymptomatic high-risk population. However, further studies are required to validate the findings of this study.
abstract
This abstract is available on the publisher's site.
Access this abstract nowOBJECTIVES
Noninvasive stool DNA-based methylation testing has emerged as an effective strategy for the early colorectal cancer (CRC) detection. Syndecan 2 (SDC2) methylation frequently occurs in all stages of CRC; therefore, this study aimed to evaluate the clinical performance of a stool DNA-based SDC2 methylation test for detecting CRC in asymptomatic or high-risk CRC populations.
DESIGN
This multicenter prospective study was conducted to determine the clinical performance of the SDC2 methylation test on stool DNA using real-time polymerase chain reaction. Stool samples were collected from asymptomatic individuals prior to colonoscopy, and the test results were independently analyzed via comparison with colonoscopic findings and pathological outcomes as reference standards.
RESULTS
Of the 1,124 evaluable participants, 20 had CRC, 73 had advanced adenomatous (AA) polyps (≥1.0 cm), 469 had nonadvanced adenomatous (NAA) polyps (<1.0 cm), 178 had nonneoplastic polyps (NNP), and 384 had negative colonoscopy results. The stool SDC2 methylation test had a sensitivity and specificity of 95.0% and 81.5%, respectively, for detecting CRC, while the sensitivity for detecting AA polyps and CRC was 58.1%. The rate of adenoma detection increased with polyp size (P<0.01), and sensitivity was not associated with CRC stage (P=0.864).
CONCLUSION
The stool DNA-based SDC2 methylation test attained a high sensitivity for CRC detection in an asymptomatic high-risk population. Further large-scale clinical studies are required to validate the clinical utility of this test as a population-based CRC screening tool.
Additional Info
Disclosure statements are available on the authors' profiles:
Colorectal cancer (CRC) screening needs are rapidly increasing, particularly since the expansion of the screening age that now includes all 45- to 50-year-old individuals at average risk. The heightened awareness of the possibility of CRC developing among younger persons is also contributing to an expanded demand for colonoscopies as this has resulted in a lower threshold to perform this test for diagnostic purposes in most practices.
In the current context, it is of particular interest to witness the development of multiple stool- and blood-based tests as some may eventually be added to the currently recommended noninvasive screening options: fecal immunochemical test and multitarget stool DNA test (Cologuard®, Exact Sciences).
Aberrant DNA methylation is a common molecular alteration observed in CRC and several studies have shown the capacity to detect these alterations from exfoliated colorectal cells. Hypermethylation of the syndecan-2 (SDC2) promoter region is a frequent epigenetic change present in colorectal neoplasms, including advanced adenomas. These changes have been identified in stool samples.1 A previous Chinese study reported that this test had a sensitivity of 83.8% for CRC and 42.1% for advanced adenomas with a specificity of 98.0%.2
The current study is a multicenter prospective clinical trial to evaluate the clinical performance of a stool DNA–based SDC2 methylation test as a screening tool in asymptomatic average- and above average–risk individuals from Korea. The test determined promoter region methylation of SDC2 through RT-PCR using a methylated SDC2 linear target enrichment and quantitative methylation-specific real-time PCR (EarlyTect® Colon Cancer Test, Genomictree, Inc.)1
The overall sensitivity of the test was 95.0% (95% CI, 75.1%–99.9%; 19/20) for detecting CRC (stages 0–IV), and 47.9% (35/73; 95% CI, 36.1%–59.9%) for advanced adenomatous polyps, remarkably similar to the newest generation of the Cologuard® test. On the other hand, overall specificity for the subjects with negative results on colonoscopy was quote low — 81.5% compared to 92.7% for Cologuard®.
Noninvasive CRC screening tests are rapidly evolving and there is no doubt that with time they will be essential screening tools.
References