KCNQ5 and C9orf50 Methylation in Stool DNA for Early Detection of Colorectal Cancer

Cao, Yaping; Zhao, Guodong; Yuan, Mufa; Liu, Xiaoyu; Ma, Yong; Cao, Yang; Miao, Bei; Zhao, Shuyan; Li, Danning; Xiong, Shangmin; Zheng, Minxue; Fei, Sujuan

doi:10.3389/fonc.2020.621295

Cited by 15 publications

(13 citation statements)

References 56 publications

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“…As single biomarkers, CLIP4 was evaluated in one study [ 72 ], TWIST1 in three articles [ 73 , 74 , 75 ], and LINE-1 in two [ 76 , 77 ]. A panel of methylated biomarkers was also employed—C9orf50 was assessed together with CLIP4 and KCNQ5 [ 78 ], with TWIST1 [ 79 ] or just with KCNQ5 [ 80 ]. Other potential biomarkers and their performance are displayed in Table S4 [ 81 , 82 , 83 , 84 , 85 , 86 , 87 , 88 , 89 , 90 ].…”

Section: Resultsmentioning

confidence: 99%

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

Anghel

Ioniță-Mîndrican

Luca

et al. 2021

Cancers

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In CRC, screening compliance is decreased due to the experienced discomfort associated with colonoscopy, although this method is the gold standard in terms of sensitivity and specificity. Promoter DNA methylation (hypomethylation or hypermethylation) has been linked to all CRC stages. Study objectives: to systematically review the current knowledge on approved biomarkers, reveal new potential ones, and inspect tactics that can improve performance. This research was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines; the risk of bias was evaluated using the revised Quality Assessment of Diagnostic Accuracy Studies criteria (QUADAS-2). The Web of Science® Core Collection, MEDLINE® and Scopus® databases were searched for original articles published in peer-reviewed journals with the specific keywords “colorectal cancer”, “early detection”, “early-stage colorectal cancer”, “epigenetics”, “biomarkers”, “DNA methylation biomarkers”, “stool or blood or tissue or biopsy”, “NDRG4”, “BMP3”, “SEPT9”, and “SDC2”. Based on eligibility criteria, 74 articles were accepted for analysis. mSDC2 and mSEPT9 were frequently assessed in studies, alone or together as part of the ColoDefense panel test—the latter with the greatest performance. mBMP3 may not be an appropriate marker for detecting CRC. A panel of five methylated binding sites of the CTCF gene holds the promise for early-stage specific detection of CRC. CRC screening compliance and accuracy can be enhanced by employing a stool mt-DNA methylation test.

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Section: Resultsmentioning

confidence: 99%

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

Anghel

Ioniță-Mîndrican

Luca

et al. 2021

Cancers

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“…Recently, a sensitivity of 77.3–85.9% and specificity of 91.5–95% has been shown for the stool-based methylated KCNQ and C9orf50 for all stage CRC detection. And when methylated C9orf50 and KCNQ5 were combined, the sensitivity for CRC detection was improved to 88.4% [ 41 ]. In addition, the methylation of multiple genes ( vimentin , NDRG4 , BMP3 , and TFPI2 ) combine with KRAS mutations in stool DNA were reported by Ahlquist et al, this test was able to detect CRC and precancerous adenoma with sensitivities of 85 and 54%, respectively, at a specificity of 90% [ 42 ].…”

Section: Discussionmentioning

confidence: 99%

“…These observed clinical sensitivity and specificity results were comparable with the result reported by Han et al [ 36 ] and higher than aforementioned studies [ 9 , 31 ]. Since most other markers have not been reported for more detailed evaluation of the clinical performance of detecting different stages of CRC, the sensitivity of methylated SDC2 for all stage CRC could be compared to those of methylated C9orf50 and KCNQ5 [ 41 ], which were very similar among all three methylation markers. Therefore, using detection of two SDC2 methylation fragments can improve clinical performance for the early diagnosis of CRC, without losing specificity.…”

Section: Discussionmentioning

confidence: 99%

A novel method for early detection of colorectal cancer based on detection of methylation of two fragments of syndecan-2 (SDC2) in stool DNA

Qin

Gai

et al. 2022

BMC Gastroenterol

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Background Methylated 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. Methods A 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). Results The 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. Conclusions This 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.

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“…After excluding unqualified samples (only Stage I/II samples were selected), there were 268 primary carcinoma samples and 239 normal samples. After normalization using ‘champ.norm’ function in the package R ‘Champ’ and filtration by the probe annotated by the corresponding annotation files for each data set, intact data of candidate methylated genes (SDC2, NDRG4, KCNQ5, WIF1, TFPI2, and ALX4), which were selected based on a PubMed library literature search, were collected and analyzed using the package R ‘Champ’ with an adjusted p-value <0.05 and a deltaBeta value >0.2 ( 13 , 21 – 23 ).…”

Section: Methodsmentioning

confidence: 99%

A Novel Stool Methylation Test for the Non-Invasive Screening of Gastric and Colorectal Cancer

Gong²,

Zhao

et al. 2022

Front. Oncol.

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BackgroundBecause of poor compliance or low sensitivity, existing diagnostic approaches are unable to provide an efficient diagnosis of patients with gastric and colorectal cancer. Here, we developed the ColoCaller test, which simultaneously detects the methylation status of the SDC2, TFPI2, WIF1, and NDRG4 genes in stool DNA, to optimize the screening of gastric and colorectal cancer in high-risk populations.MethodsA total of 217 stool samples from patients with gastrointestinal cancer and from patients with negative endoscopy were prospectively collected, complete with preoperative and postoperative clinical data from patients. The methylation of these samples was detected using ColoCaller, which was designed by selecting CpGs with a two-step screening strategy, and was interpreted using a prediction model built using libSVM to evaluate its clinical value for gastric and colorectal cancer screening.ResultsCompared to pathological diagnosis, the sensitivity and specificity of the ColoCaller test in 217 stool DNA samples were 95.56% and 91.86%, respectively, for colorectal cancer, and 67.5% and 97.81%, respectively, for gastric cancer. The detection limit was as low as 1% in 8 ng of DNA.ConclusionIn this study, we developed and established a new test, ColoCaller, which can be used as a screening tool or as an auxiliary diagnostic approach in high-risk populations with gastric and colorectal cancer to promote timely diagnosis and treatment.

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KCNQ5 and C9orf50 Methylation in Stool DNA for Early Detection of Colorectal Cancer

Cited by 15 publications

References 56 publications

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

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

A novel method for early detection of colorectal cancer based on detection of methylation of two fragments of syndecan-2 (SDC2) in stool DNA

A Novel Stool Methylation Test for the Non-Invasive Screening of Gastric and Colorectal Cancer

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