Abstract
Aberrant DNA methylation has shown promise as a biomarker for the early detection of cancer. To discover novel genes frequently methylated at an early stage in colorectal cancer (CRC), DNA microarray analysis coupled with enriched methylated DNA was performed in primary tumors and compared with adjacent nontumor tissues of 12 patients with CRC at stages I to IV. Stepwise filtering for candidate selection in microarray data analysis yielded a set of genes that are highly methylated across all CRC tumors and that can be used as a composite biomarker for CRC detection. Verification assay identified the SDC2 gene as a potential methylation biomarker for early CRC detection. In clinical validation in tissues from 139 CRC patients, a much higher level of aberrant SDC2 methylation was measured in most primary tumors (97.8%), compared with corresponding nontumor tissue of CRC patients, irrespective of clinical stage. Clinical validation of SDC2 methylation in serum DNA from CRC patients (n = 131) at stages I to IV and from healthy individuals (n = 125) by quantitative methylation-specific PCR demonstrated a high sensitivity of 87.0% (95% CI, 80.0% to 92.3%) in detecting cancers, with a specificity of 95.2% (95% CI, 89.8% to 98.2%). Importantly, sensitivity at stage I was 92.3%, indicating the potential of SDC2 methylation as a blood-based DNA test for early detection of CRC.
| Original language | English |
|---|---|
| Pages (from-to) | 498-507 |
| Number of pages | 10 |
| Journal | Journal of Molecular Diagnostics |
| Volume | 15 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - 2013 Jul 1 |
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All Science Journal Classification (ASJC) codes
- Pathology and Forensic Medicine
- Molecular Medicine
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Genome-wide identification and validation of a novel methylation biomarker, SDC2, for blood-based detection of colorectal cancer. / Oh, Taejeong; Kim, Nayoung; Moon, Youngho; Kim, Myung Soon; Hoehn, Benjamin D.; Park, Chan Hee; Kim, Tae Soo; Kim, Nam Kyu; Chung, Hyun Cheol; An, Sungwhan.
In: Journal of Molecular Diagnostics, Vol. 15, No. 4, 01.07.2013, p. 498-507.Research output: Contribution to journal › Article
TY - JOUR
T1 - Genome-wide identification and validation of a novel methylation biomarker, SDC2, for blood-based detection of colorectal cancer
AU - Oh, Taejeong
AU - Kim, Nayoung
AU - Moon, Youngho
AU - Kim, Myung Soon
AU - Hoehn, Benjamin D.
AU - Park, Chan Hee
AU - Kim, Tae Soo
AU - Kim, Nam Kyu
AU - Chung, Hyun Cheol
AU - An, Sungwhan
PY - 2013/7/1
Y1 - 2013/7/1
N2 - Aberrant DNA methylation has shown promise as a biomarker for the early detection of cancer. To discover novel genes frequently methylated at an early stage in colorectal cancer (CRC), DNA microarray analysis coupled with enriched methylated DNA was performed in primary tumors and compared with adjacent nontumor tissues of 12 patients with CRC at stages I to IV. Stepwise filtering for candidate selection in microarray data analysis yielded a set of genes that are highly methylated across all CRC tumors and that can be used as a composite biomarker for CRC detection. Verification assay identified the SDC2 gene as a potential methylation biomarker for early CRC detection. In clinical validation in tissues from 139 CRC patients, a much higher level of aberrant SDC2 methylation was measured in most primary tumors (97.8%), compared with corresponding nontumor tissue of CRC patients, irrespective of clinical stage. Clinical validation of SDC2 methylation in serum DNA from CRC patients (n = 131) at stages I to IV and from healthy individuals (n = 125) by quantitative methylation-specific PCR demonstrated a high sensitivity of 87.0% (95% CI, 80.0% to 92.3%) in detecting cancers, with a specificity of 95.2% (95% CI, 89.8% to 98.2%). Importantly, sensitivity at stage I was 92.3%, indicating the potential of SDC2 methylation as a blood-based DNA test for early detection of CRC.
AB - Aberrant DNA methylation has shown promise as a biomarker for the early detection of cancer. To discover novel genes frequently methylated at an early stage in colorectal cancer (CRC), DNA microarray analysis coupled with enriched methylated DNA was performed in primary tumors and compared with adjacent nontumor tissues of 12 patients with CRC at stages I to IV. Stepwise filtering for candidate selection in microarray data analysis yielded a set of genes that are highly methylated across all CRC tumors and that can be used as a composite biomarker for CRC detection. Verification assay identified the SDC2 gene as a potential methylation biomarker for early CRC detection. In clinical validation in tissues from 139 CRC patients, a much higher level of aberrant SDC2 methylation was measured in most primary tumors (97.8%), compared with corresponding nontumor tissue of CRC patients, irrespective of clinical stage. Clinical validation of SDC2 methylation in serum DNA from CRC patients (n = 131) at stages I to IV and from healthy individuals (n = 125) by quantitative methylation-specific PCR demonstrated a high sensitivity of 87.0% (95% CI, 80.0% to 92.3%) in detecting cancers, with a specificity of 95.2% (95% CI, 89.8% to 98.2%). Importantly, sensitivity at stage I was 92.3%, indicating the potential of SDC2 methylation as a blood-based DNA test for early detection of CRC.
UR - http://www.scopus.com/inward/record.url?scp=84879289642&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84879289642&partnerID=8YFLogxK
U2 - 10.1016/j.jmoldx.2013.03.004
DO - 10.1016/j.jmoldx.2013.03.004
M3 - Article
C2 - 23747112
AN - SCOPUS:84879289642
VL - 15
SP - 498
EP - 507
JO - Journal of Molecular Diagnostics
JF - Journal of Molecular Diagnostics
SN - 1525-1578
IS - 4
ER -