Genome-Wide Identification and Validation of a Novel Methylation Biomarker, SDC2, for Blood-Based Detection of Colorectal Cancer

Oh, Taejeong; Kim, Nayoung; Moon, Young‐Jin; Kim, Myung Soon; Hoehn, Benjamin D.; Park, Chan Hee; Kim, Tae Soo; Kim, Nam Kyu; Chung, Hyun Cheol; An, Sungwhan

doi:10.1016/j.jmoldx.2013.03.004

Cited by 145 publications

(147 citation statements)

References 30 publications

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“…CEA + ALU115 + ALU247/1 15 = SENS 85.57%SPEC 97.27%Yes (levels significantly different between primary CRC and polyps/controls)NoALU247/115 of serum DNA0.8973.0897.270.52 ng/mlQi et al (2013) [52]ProspectiveAlu-based cell-free DNA31 CRC30 polyp92 healthySerum0.90464.598.9634.9 ng/mLYes (CEA AUC 0.681, CA19-9 AUC 0.651-polyp versus CRC)NoNoOh et al (2013) [17]ProspectiveSDC2 methylation in DNA131 CRC125 healthySerumND8795.20.936NoSens 92%stage IYesRodia et al (2016) [53]Meta-analysisTSPAN 867 CRC, 67 controlWhole blood0.75183.658.2N/DNoNoNoLGALS40.74682.161.2N/DCOL1A20.71873.159.7N/DCEACAM 60.63265.761.2N/D…”

Section: Resultsmentioning

confidence: 99%

“…It is also expressed in pancreatic epithelial cells. SDC2 methylation of DNA in a prospective study by Oh T et al in 2013 showed sensitivity of detecting early CRC of 92% although this needs further validation in a larger study [17]. …”

Section: Resultsmentioning

confidence: 99%

“…From our review the following markers were found to have a sensitivity ≥ 70% and specificity ≥ 90%: interleukin 8 [25], NEAT_v2, SDC2 methylation of DNA [17], SEPT9 [14, 26], CA11-19 [22] and DC-SIGN/DC-SIGNR [24]. This cutoff sensitivity and specificity were used because they will discriminate markers which show promise in detecting CRC, and are comparable to the currently available biomarkers.…”

Section: Resultsmentioning

confidence: 99%

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Systematic review of blood diagnostic markers in colorectal cancer

et al. 2018

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The purpose of this systematic review was to compare the diagnostic ability of blood markers for colorectal cancer (CRC). A systematic review of the literature for diagnostic blood markers for primary human colorectal cancer over the last 5 years was performed. The primary outcome was to assess the diagnostic ability of these markers in diagnosing colorectal cancer. The secondary outcome was to see whether the marker was compared to other markers. The tertiary outcome was to assess diagnostic ability in early versus late CRC, including stage IV disease. We identified 51 studies (29 prospective, 14 retrospective, and 8 meta-analyses). The markers were divided in broadly four groups: nucleic acids (RNA/DNA/messenger RNA/microRNAs), cytokines, antibodies, and proteins. The most promising circulating markers identified among the nucleid acids were NEAT_v2 non-coding RNA, SDC2 methylated DNA, and SEPT9 methylated DNA. The most promising cytokine to detect CRC was interleukin 8, and the most promising circulating proteins were CA11-19 glycoprotein and DC-SIGN/DC-SIGNR. Sensitivities of these markers for detecting primary colorectal carcinoma ranged from 70 to 98% and specificities from 84 to 98.7%. The best studied blood marker was SEPT9 methylated DNA, which showed great variability with sensitivities ranging from 48.2 to 95.6% and specificities from 80 to 98.9%, making its clinical applicability challenging. If combined with fecal immunochemical test (FIT), the sensitivity improved from 78 to 94% in detecting CRC. Methylated SEPT9, methylated SDC2, and -SIGN/DC-SIGNR protein had better sensitivity and specificity than CEA or CA 19-9. With the exception of SEPT9 which is currently being implemented as a screening test for CRC all other markers lacked reproducibility and standardization and were studied in relatively small population samples.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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Systematic review of blood diagnostic markers in colorectal cancer

et al. 2018

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“…In addition, the associated costs of implementing and executing PCR-based techniques are lower, allowing the initial study of several candidate ROIs. PCR-based approaches also offer the advantage of a lower burden of false discoveries and the ability to confirm a large number of ROIs identified in genome-wide screening of a few samples (70). …”

Section: Discussionmentioning

confidence: 99%

Optimizing methodologies for PCR-based DNA methylation analysis

et al. 2013

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Comprehensive analysis of DNA methylation patterns is critical for understanding the molecular basis of many human diseases. While hundreds of PCR-based DNA methylation studies are published every year, the selection and implementation of appropriate methods for these studies can be challenging for molecular genetics researchers not yet familiar with methylation analysis. Here we review the most commonly used PCR-based DNA methylation analysis techniques: bisulfite sequencing PCR (BSP), methylation specific PCR (MSP), MethyLight, and methylation-sensitive high resolution melting (MS-HRM). We provide critical analysis of the strengths and weaknesses of each approach as well as a series of guidelines to assist in selecting and implementing an appropriate method.

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“…A number of methylation biomarkers have been found in circulating cell-free DNA (ccfDNA) in blood and are promising avenues to address this clinical need (10,(12)(13)(14)(15)(16)(17). Among those that have been rigorously studied, methylated SEPT9 6 (septin 9) is the most well characterized (18,19 ).…”

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confidence: 99%