Evaluating the Clinical Performance of a Dual-Target Stool DNA Test for Colorectal Cancer Detection

Wan, Kangkang; Shang, Jian; Zhang, Guannan; Kong, Lingjun; zhang, Feng; Guo, Ye; Dou, Yaling; Lin, Jie

doi:10.1016/j.jmoldx.2021.10.012

Cited by 15 publications

(9 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A recent study on a dual-target stool DNA test (methylated SDC2 and TFPI2) showed a sensitivity of 95.31% for CRC, exceeding the performance of either target alone. Meanwhile, its specificity was reduced from 100% by SDC2 alone to 96.67% in dual-target test [20]. Similar trends were observed in this study, the sensitivities of CRC increased from 79.4% by SDC2 and 67.6% by SEPT9 alone to 88.2% in combined.…”

Section: Discussionsupporting

confidence: 88%

A simplified multiplex methylated DNA testing for early detection of colorectal cancer in stool DNA

et al. 2022

View full text Add to dashboard Cite

Background ColoDefense1.0 assay has demonstrated its excellent sensitivity and specificity for early detection of colorectal cancer (CRC) by detecting the methylation levels of SDC2 and SEPT9, while exhibited limitations on relatively large sample capacity required and limited detection throughput by applying triplicate PCR reactions for each sample. In this study, ColoDefense1.0 was simplified and optimized into ColoDefense2.0 in a single PCR reaction. Methods A total 529 stool specimens were collected, and 244 CRC patients, 34 patients with advanced adenomas (AA), 64 with small polyps (SP) and 187 control subjects were divided in training and validation cohorts. Methylation levels of SEPT9 and SDC2 were examined by qPCR reactions in triplicate or single. Results The stool DNA quantity stored in preservative buffer at 37 °C up to 7 days exhibited no significant decrease. In the training cohort, when the number of replicates reduced from 3 to 1, the overall performance of ColoDefense2.0 was identical to that of ColoDefense1.0, showing sensitivities of 71.4% for AA and 90.8% for all stage CRC with a specificity of 92.9%. In the validation cohort, sensitivities of SP, AA and CRC using ColoDefense2.0 were 25.0%, 55.0% and 88.2%, increased from 14.1% (20.3%), 40.0% (40.0%) and 79.4% (67.6%) using SDC2 (SEPT9) alone; along with an overall specificity of 90.2%, decreased from 94.1% (95.1%) using SDC2 (SEPT9) alone. Conclusion The simplified ColoDefense test maintained the overall performance while reduced the number of PCR reactions to 1/3, and provided an effective and convenient tool to detect early CRC and precancerous lesions and potentially improve the compliance of screening.

show abstract

Section: Discussionsupporting

confidence: 88%

A simplified multiplex methylated DNA testing for early detection of colorectal cancer in stool DNA

et al. 2022

View full text Add to dashboard Cite

show abstract

“…In previous multicentre clinical trial screening research, the sensitivity of sDNA testing for CRC ranged from 71.56% to 90.0%, while the specificity ranged from 88.2% to 100%, indicating a good diagnostic effect. 13 , 15 , 24–26 However, SDC2 had an overall sensitivity of 100% and a specificity of 79.3% for CRC in this study, which may be related to the small CRC sample size. With regard to AA and ACN, the consistency of the colonoscopy findings of the present study was poor in comparison to a previous study.…”

Section: Discussioncontrasting

confidence: 53%

A Comparison of Single and Combined Schemes of Asia-Pacific Colorectal Screening, Faecal Immunochemical and Stool Deoxyribonucleic Acid Testing for Community Colorectal Cancer Screening

Ze¹,

Tu²,

Zhang³

et al. 2023

JMDH

View full text Add to dashboard Cite

Objective To compare the screening efficacy of colonoscopy and pathologically confirmed single and combined Asia-Pacific colorectal screening (APCS), faecal immunochemical testing (FIT) and stool deoxyribonucleic acid (sDNA) testing protocols. Methods From April 2021 to April 2022, 842 volunteers participated in primary colorectal cancer (CRC) screenings using APCS scoring, FIT and sDNA testing and 115 underwent a colonoscopy. One hundred high-risk participants were then identified from the results of both processes. The differences in the three CRC screening tests in combination with the colonoscopy pathology diagnostics were evaluated using Cochran’s Q test, the Dunn–Bonferroni test and area under the receiver operating characteristic curve (AUC) value analysis. Results Both FIT and sDNA testing demonstrated a 100% performance in detecting CRC. For advanced adenoma, the sensitivity of the FIT + sDNA test scheme (double positive) was 29.2%, and the sensitivities of the combined FIT + sDNA test and APCS scoring + sDNA test schemes were 62.5% and 95.8%, respectively. The FIT + sDNA testing kappa value of advanced colorectal neoplasia was 0.344 ( p = 0.011). The sensitivity for nonadvanced adenoma of the APCS score + sDNA test scheme was 91.1%. In terms of positive results, the sensitivity of the APCS score + FIT + sDNA detection protocol was significantly higher than that of the APCS score, FIT, sDNA detection, and FIT + sDNA detection methods (adjusted p < 0.001, respectively). For the FIT + sDNA test, the kappa value was 0.220 ( p = 0.015) and the AUC was 0.634 ( p = 0.037). The specificity of the FIT + sDNA test scheme was 69.0%. Conclusion The FIT + sDNA test scheme demonstrated superior diagnostic efficacy, and the combined APCS score + FIT + sDNA test scheme demonstrated remarkable improvements in CRC screening efficiency and sensitivity for detecting positive lesions.

show abstract

“…Several studies have suggested a better performance of combined multi-targets for CRC early detection than a single biomarker [ 25 – 27 ]. We observed an improved detection sensitivity when combining the two targets in our previous studies [ 28 , 29 ], but not all CRC samples can be detected. During clinical practice, some CRC samples were detected only by a single or no target, reflecting the preference of different targets in distinguishing CRCs from normal samples, which directly affects the target utility.…”

Section: Introductionmentioning

confidence: 49%

The methylation of SDC2 and TFPI2 defined three methylator phenotypes of colorectal cancer

et al. 2022

View full text Add to dashboard Cite

Background Methylated SDC2 and TFPI2 are widely used for colorectal cancer (CRC) detection. However, they often miss some CRCs, which directly diminishes the sensitivity. Further investigations of the underlying mechanisms leading to the missed samples will facilitate developing more eligible methylation markers. Methods CRC samples from TCGA and GEO datasets were divided into three groups, High-methylation/ High-methylation (HH), High-methylation/Low-methylation (HL), and Low-methylation/Low-methylation (LL) according to the methylation status of SDC2 and TFPI2 promoters. Variations in age, tumor location and microsatellite instable were then assessed between the three groups and verified in our custom cohort. Results Samples of HL group preferred to derive from left-sided CRCs (P < 0.05). HH samples showed the highest microsatellite instability and mutation load (mean nonsynonymous mutations for HH/HL/LL: 10.55/3.91/7.02, P = 0.0055). Almost all mutations of BRAF, one of the five typical CpG island methylator phenotype (CIMP) related genes, were observed in HH group (HH/HL/LL: 51/0/1, P = 0.018). Besides, older patients were frequently found in HH group. Expression analysis identified 37, 84, and 22 group-specific differentially expressed genes (DEGs) for HH, HL, and LL, respectively. Functional enrichment analysis revealed that HH-specific DEGs were mainly related to transcription regulation, while LL-specific DEGs were enriched in the biological processes of extracellular matrix interaction and cell migration. Conclusions The current study revealed that the performance of methylation-based markers might be affected by tumor location, patient age, mutation load and MSI, and these respective sides should be considered when developing new methylation markers for CRC detection.

show abstract

Evaluating the Clinical Performance of a Dual-Target Stool DNA Test for Colorectal Cancer Detection

Cited by 15 publications

References 51 publications

A simplified multiplex methylated DNA testing for early detection of colorectal cancer in stool DNA

A simplified multiplex methylated DNA testing for early detection of colorectal cancer in stool DNA

A Comparison of Single and Combined Schemes of Asia-Pacific Colorectal Screening, Faecal Immunochemical and Stool Deoxyribonucleic Acid Testing for Community Colorectal Cancer Screening

The methylation of SDC2 and TFPI2 defined three methylator phenotypes of colorectal cancer

Contact Info

Product

Resources

About