Dataset Information

Identification of two methylated fragments of an SDC2 CpG island using a sliding window technique for early detection of colorectal cancer.

ABSTRACT: Colorectal cancer (CRC) is one of the most common cancer types globally with a 5-year survival rate of < 50% in China. Aberrant DNA methylation is one of the hallmarks of tumor initiation, progression, and metastasis. Here, we investigated the clinical performance of two differentially methylated regions (DMRs) in SDC2 CpG islands for the detection of CRC. A sliding window technique was used to identify the DMRs, and methylation-specific PCR assay was used to assess the DMRs in 198 CRC samples and 54 normal controls. Two DMRs (DMR2 and DMR5) were identified using The Cancer Genome Atlas (TCGA) data, and the hypermethylation of DMR2 and DMR5 was detected in 90.91% (180/198) and 89.90% (178/198) of CRC samples, respectively. When combining DMR2 and DMR5, the sensitivity for CRC detection was 94.4% higher than that of DMR2 or DMR5 alone. Based on the above results, we propose using DMR2 and DMR5 as a sensitive biomarker to detect CRC.

SUBMITTER: Li R

PROVIDER: S-EPMC8255834 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature

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Identification of two methylated fragments of an SDC2 CpG island using a sliding window technique for early detection of colorectal cancer.

Li Ruibin R Qu Bing B Wan Kangkang K Lu Changming C Li Tingting T Zhou Fuxiang F Lin Jun J

FEBS open bio 20210607 7

Colorectal cancer (CRC) is one of the most common cancer types globally with a 5-year survival rate of < 50% in China. Aberrant DNA methylation is one of the hallmarks of tumor initiation, progression, and metastasis. Here, we investigated the clinical performance of two differentially methylated regions (DMRs) in SDC2 CpG islands for the detection of CRC. A sliding window technique was used to identify the DMRs, and methylation-specific PCR assay was used to assess the DMRs in 198 CRC samples a ...[more]

PMID: 33955718

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Project description:BackgroundMethylated SDC2 has been proved as a diagnostic marker for human colorectal cancer (CRC), noninvasive stool DNA-based methylation testing also emerges as a novel approach for detecting CRC. The aim of this study was to evaluate the clinical performance of stool DNA-based SDC2 methylation test by a new qPCR detection reagent for early detection of CRC.MethodsA new qPCR detection reagent contained two differentially methylated regions in SDC2 CpG islands for the detection of CRC was used in this study. Performance of the SDC2 methylation detection reagent was evaluated by analyzing limit of detection, precision, and specificity. The effect of interfering substances on assay performance was also tested. 339 subjects (102 CRC patients, 50 patients with advanced adenomas, 39 patients with non-advanced adenomas, 18 colitis patients and 130 normal individuals) from the China-Japan Friendship Hospital were evaluated. Approximately 2.5 g of stool sample was collected from each participant. Stool DNA was extracted and bisulfite-converted, followed by qPCR assay, which contained two pairs of primers for the methylation detection of two fragments of the SDC2 gene (named SDC2-A and SDC2-B). The diagnostic value of this test in CRC was evaluated by calculating receiver operating characteristic (ROC) curve, and value of the area under the curve (AUC).ResultsThe test kit was able to detect methylated SDC2 in stool DNA samples with concentrations as low as 90 copies/μL in 100% of replicates. The sensitivity for detecting CRC by methylated SDC2-A alone was 85.29% (95% CI 77.03-91.00%) with a specificity of 96.15% (95% CI 91.08-98.58%). The sensitivity by methylated SDC2-B alone was 83.33% (95% CI 74.82-89.42%) with a specificity of 97.69% (95% CI 93.14-99.51%). However, when methylated SDC2-A and methylated SDC2-B were combined, the sensitivity for CRC detection improved to 87.25% (95% CI 79.27-92.53%) with a specificity of 94.62% (95% CI 89.11-97.56%). Further, the detection reagent achieved ROC-AUC 0.874 (95% CI 0.822-0.927) for SDC2-A, 0.906 (95% CI 0.859-0.952) for SDC2-B, and 0.939 (95% CI 0.902-0.977) for SDC2-Combine A&B.ConclusionsThis study validated the capability of stool DNA-based SDC2 methylation test for early screening of CRC, and combined detection of two fragments of SDC2 gene could improve detection sensitivity.

Dataset Information

Identification of two methylated fragments of an SDC2 CpG island using a sliding window technique for early detection of colorectal cancer.

Publications

Identification of two methylated fragments of an SDC2 CpG island using a sliding window technique for early detection of colorectal cancer.

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