title: Genome-wide identification and validation of a novel methylation biomarker, SDC2, for blood-based detection of colorectal cancer.
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.
authors.affiliation: Genomictree, Inc., Daejeon, South Korea.
authors.forename: TaeJeong
authors.initials: T
authors.lastname: Oh
authors.forename: Nayoung
authors.initials: N
authors.lastname: Kim
authors.forename: Youngho
authors.initials: Y
authors.lastname: Moon
authors.forename: Myung Soon
authors.initials: MS
authors.lastname: Kim
authors.forename: Benjamin D
authors.initials: BD
authors.lastname: Hoehn
authors.forename: Chan Hee
authors.initials: CH
authors.lastname: Park
authors.forename: Tae Soo
authors.initials: TS
authors.lastname: Kim
authors.forename: Nam Kyu
authors.initials: NK
authors.lastname: Kim
authors.forename: Hyun Cheol
authors.initials: HC
authors.lastname: Chung
authors.forename: Sungwhan
authors.initials: S
authors.lastname: An
mesh_terms: D000328:Adult; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood*; D015179:Colorectal Neoplasms / Q000097:blood / Q000175:diagnosis* / Q000235:genetics; D019175:DNA Methylation; D055088:Early Detection of Cancer; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D015894:Genome, Human; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D053669:Syndecan-2 / Q000096:biosynthesis / Q000097:blood*
chemical_list: D014408:Biomarkers, Tumor; C508245:SDC2 protein, human; D053669:Syndecan-2