Stool DNA test targeting methylated syndecan-2 (SDC2) as a noninvasive screening method for colorectal cancer

Abstract

Despite the steadily increasing worldwide incidence of colorectal cancer (CRC), an effective noninvasive approach for early detection of CRC is still under investigation. The guaiac-based fecal occult blood test (FOBT) and fecal immunochemical test (FIT) have gained popularity as noninvasive CRC screening tests owing to their convenience and relatively low costs. However, the FOBT and FIT have limited sensitivity and specificity. To develop a noninvasive tool for the detection of CRC, we investigated the sensitivity, specificity, and accuracy of a stool DNA test targeting methylated syndecan-2 (SDC2), which is frequently methylated in patients with CRC. The present study enrolled 62 patients diagnosed as having stage 0-IV CRC and 76 healthy participants between July 2018 and June 2019 from two institutions. Approximately 4.5 g of stool sample was collected from each participant for detection of human methylated SDC2 gene. In total, 48 of 62 (77.4%) patients with CRC showed positive results, whereas 67 out of 76 (88.2%) healthy participants showed negative results. The area under the curve of the receiver operating characteristic curve constructed was 0.872 for discrimination between patients with CRC and healthy individuals. The present study highlights the potential of the fecal methylated SDC2 test as a noninvasive detection method for CRC screening with a relatively favorable sensitivity of 77.4%, a specificity of 88.2% and a positive predictive value of 84.2% compared with other available fecal tests. Further multicenter clinical trials comprising subjects of varied ethnicities are required to validate this test for the mass screening of patients with CRC.

Detection of Postcolonoscopy Colorectal Neoplasia by Multi-target Stool DNA

“…Because no cancers were observed ≤5 years after previous negative screening colonoscopy, and the rates of advanced adenoma ≤5 years were the same as seen 6–9 years after colonoscopy, we propose that mt-sDNA be studied in the future as an interval screening test 5 years after negative screening colonoscopy with or without comparison to FIT. Although not yet available in the United States, there are other methylated stool-based tests in development ( 42 ) and in commercial use ( 43 , 44 ). Although these tests will require validation and approval in the United States, prospective comparison between the stool-based tests with concurrent colonoscopy will be invaluable for assessing differences in test performance and potential use as an adjunct to colonoscopy.…”

Promising Epigenetic Biomarkers for the Early Detection of Colorectal Cancer: A Systematic Review

“…We examined the last five years’ literature for methylated genes currently targeted by FDA or NMPA screening kits: mSDC2, mSEPT9, mNDRG4, and mBMP3. With our specific filters, we found six studies dedicated to mSDC2 [ 33 , 34 , 35 , 36 , 37 , 38 ] and seven studies for mSEPT9 [ 39 , 40 , 41 , 42 , 43 , 44 , 45 ]; two described mBMP3 performance [ 46 , 47 ], while no study evaluated mNDRG4 alone. A multi-target approach evaluating these biomarkers and others was employed in 16 studies, 5 of them deciphering mSDC2 and mSEPT9 performance [ 48 , 49 , 50 , 51 , 52 ].…”

“…SDC2 is a transmembrane protein implicated in cellular proliferation, migration, cell–matrix interaction, and angiogenesis [ 53 ]. SDC2 methylation ( Table S1 ) was quantified in two studies using tissue and stool [ 33 , 34 ]; one study used tissue and bowel lavage [ 35 ], and three studies evaluated DNA methylation only in stool [ 36 , 37 , 38 ]. Only one study had paired samples [ 33 ].…”

“…We examined the last five years' literature for methylated genes currently targeted by FDA or NMPA screening kits: mSDC2, mSEPT9, mNDRG4, and mBMP3. With our specific filters, we found six studies dedicated to mSDC2 [33][34][35][36][37][38] and seven studies for mSEPT9 [39][40][41][42][43][44][45]; two described mBMP3 performance [46,47], while no study evaluated We examined the last five years' literature for methylated genes currently targeted by FDA or NMPA screening kits: mSDC2, mSEPT9, mNDRG4, and mBMP3. With our specific filters, we found six studies dedicated to mSDC2 [33][34][35][36][37][38] and seven studies for mSEPT9 [39][40][41][42][43][44][45]; two described mBMP3 performance [46,47], while no study evaluated mNDRG4 alone.…”

“…With our specific filters, we found six studies dedicated to mSDC2 [33][34][35][36][37][38] and seven studies for mSEPT9 [39][40][41][42][43][44][45]; two described mBMP3 performance [46,47], while no study evaluated We examined the last five years' literature for methylated genes currently targeted by FDA or NMPA screening kits: mSDC2, mSEPT9, mNDRG4, and mBMP3. With our specific filters, we found six studies dedicated to mSDC2 [33][34][35][36][37][38] and seven studies for mSEPT9 [39][40][41][42][43][44][45]; two described mBMP3 performance [46,47], while no study evaluated mNDRG4 alone. A multi-target approach evaluating these biomarkers and others was employed in 16 studies, 5 of them deciphering mSDC2 and mSEPT9 performance [48][49][50][51][52].…”