A novel plasma based early colorectal cancer screening assay base on methylated SDC2 and SFRP2

Zhao, Guodong; Ma, Yong; Li, Hui; Li, Shiming; Zhu, Yun; Liu, Xiaoyu; Xiong, Shangmin; Liu, Yi; Miao, Ji; Fei, Sujuan; Zheng, Minxue; Zhao, Xiangwei

doi:10.1016/j.cca.2020.01.010

Cited by 28 publications

(27 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The results showed that the sensitivities of stool SpecColon test for detecting AA, early stage (0-II) CRC and stage I-IV CRC by cut-off-2 were 53.8% (7/13) [15]. Previous studies indicated that plasma mSEPT9 test, a FDA approved assay for CRC early detection, could achieve better performance with three PCR replicates when compared with single PCR reaction [20,21].…”

Section: Discussionmentioning

confidence: 97%

“…Consistently, as stool DNA originated directly from AA and CRC tissues, the mSFRP2 and mSDC2 levels in stool were higher than that in plasma, thus it is reasonable that stool SpecColon test showed higher sensitivity. Nevertheless, both plasma and stool SpecColon tests showed better performance than mSEPT9 test, especially for AA and early stage CRC detection [15,23]. China has a large population of over 1.4 billion, and approximately 700 million people (age 45-80) should access CRC screening.…”

Section: Discussionmentioning

confidence: 99%

“…The exclusion criteria of stool samples were as follows: missing or incomplete sample information, insufficient or excessive stool volume, repeated sampling, and insufficient DNA indicated by low ACTB levels (see data analysis). After exclusion of invalid samples, 291 subjects in the training cohort (111 CRC patients, 13 AA patients 12 , 44 patients with small polyps (SP) 15 and 123 healthy subjects with no evidence diseases (normal subjects)) and 129 subjects in the validation cohort (58 CRC patients, 13 AA patients, 20 SP patients and 38 normal subjects) were included for final analysis. The diagnoses of the patients were histologically confirmed by the pathologist (Table 1 ).…”

Section: Methodsmentioning

confidence: 99%

“…In recent years, several non-invasive methods based on blood or stool methylation biomarkers have been developed for CRC early detection [11][12][13][14]. We had previously demonstrated high sensitivity and specificity of a plasma-based multiplex methylated DNA test, SpecColon, for CRC early detection [15]. It detects methylated SFRP2 (mSFRP2), methylated SDC2 (mSDC2) and an internal control gene (ACTB) simultaneously in a single qPCR reaction.…”

Section: Ivyspringmentioning

confidence: 99%

See 3 more Smart Citations

Methylated SFRP2 and SDC2 in stool specimens for Colorectal Cancer early detection: A cost-effective strategy for Chinese population

Zhao¹,

Liu²,

Liu³

et al. 2021

J. Cancer

Self Cite

View full text Add to dashboard Cite

Background: The aim of this study was to evaluate the feasibility of combination of methylated SFRP2 and methylated SDC2 (SpecColon test) in stool specimens for colorectal cancer (CRC) early detection and to optimize the cutoff value of methylated SFRP2 and methylated SDC2. Methods: Approximately 5 g of stool specimen each was collected from 420 subjects (291 in the training cohort and 129 in the validation cohort). Stool DNA was extracted and bisulfite-converted, followed by detection of methylated level of SFRP2 and SDC2. Youden index was employed to determine the cutoff value. Results: The whole operating time for stool SpecColon test takes less than 5 hours. The limit of detection of combination of methylated SFRP2 and methylated SDC2 was as low as 5 pg per reaction. The optimized cutoff value was methylated SFRP2 analyzed by 3/3 rule and methylated SDC2 analyzed by 2/3 rule. In the training cohort, the sensitivities of stool SpecColon test for detecting AA and early stage CRC (stage 0-II) were 53.8% (95% CI: 26.1%-79.6%) and 89.1% (95% CI: 77.1%-95.5%) with a specificity of 93.5% (95% CI: 87.2%-96.9%), and the AUC for CRC diagnosis was 0.879 (95% CI: 0.830-0.928). Similar performance was achieved by SpecColon test also in the validation cohort, where its sensitivities for detecting AA and early stage CRC (stage 0-II) were 61.5% (95% CI: 32.3-84.9%) and 88.5% (95% CI: 68.5%-97.0%) with a specificity of 89.5% (95% CI: 74.3-96.7%). Conclusion: Combined detections of methylated SFRP2 and methylated SDC2 in stool samples demonstrated high sensitivities and specificity for the detection of AA and early stage CRC. Therefore, this combination has the potential to become an accurate and cost-effective tool for CRC early detection.

show abstract

Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Ivyspringmentioning

confidence: 99%

See 2 more Smart Citations

Methylated SFRP2 and SDC2 in stool specimens for Colorectal Cancer early detection: A cost-effective strategy for Chinese population

Zhao¹,

Liu²,

Liu³

et al. 2021

J. Cancer

Self Cite

View full text Add to dashboard Cite

show abstract

“…To improve the sensitivity of plasma methylated SEPT9 test, several strategies have been proposed during the recent years. Among such strategies, the combination of multiple biomarkers and/or methods has become an effective approach in CRC diagnosis and screening to improve sensitivity (Song et al, 2017;Zhao et al, 2020). For example, it was reported that the sensitivities for CRC detection were 72.2 and 68.0%, respectively, for SEPT9 methylation and FIT individually, but when test results for SEPT9 methylation and FIT were combined, CRC detection rate increased to 88.7% (Johnson et al, 2014).…”

Section: Discussionmentioning

confidence: 99%

Performance Comparison Between Plasma and Stool Methylated SEPT9 Tests for Detecting Colorectal Cancer

et al. 2020

Self Cite

View full text Add to dashboard Cite

Colorectal cancer (CRC) is the most common type of malignancies of the gastrointestinal tract worldwide. Plasma methylated SEPT9 test has been used clinically for CRC screening for several years, but the study about the performance comparison between plasma and stool has rarely been reported. In this study, 124 plasma samples, 100 stool samples, and 60 sets of plasma and paired stool samples were collected and tested by a methylated SEPT9 test in three PCR replicates. The results indicated methylated SEPT9 levels in stool samples were significant higher than those in plasma samples (p < 0.0001). When a plasma sample was called positive if 1 out of 3 PCR replicates was positive and a stool sample was called positive if 3 out of 3 PCR replicates were positive with a mean Cp value of less than 40.0, stool methylated SEPT9 test achieved similar sensitivity (83.3% vs 85.6%) and specificity (92.1% vs 90.1%) to those by plasma methylated SEPT9 test, and the overall concordance rate is 78.3%. However, stool methylated SEPT9 test showed 35.9 and 7.9% improvement in detecting advanced adenomas (AA) and stage I-II CRC in comparison to plasma methylated SEPT9 test. The AUC for plasma methylated SEPT9 and stool methylated SEPT9 in detecting CRC were 0.885 (95% CI: 0.832-0.938) and 0.935 (95% CI: 0.895-0.975), respectively. In conclusion, stool methylated SEPT9 test showed higher sensitivities for detection AA and early stage CRC compared with plasma methylated SEPT9 test, and stool methylated SEPT9 test may be a more suitable tool for early stage CRC screening.

show abstract

Real‐world application of a fast stool DNA test for colorectal cancer screening in primary screening positive population

Zhu

Zhao

et al. 2022

Cancer Medicine

Self Cite

View full text Add to dashboard Cite

show abstract

A novel plasma based early colorectal cancer screening assay base on methylated SDC2 and SFRP2

Cited by 28 publications

References 28 publications

Methylated SFRP2 and SDC2 in stool specimens for Colorectal Cancer early detection: A cost-effective strategy for Chinese population

Methylated SFRP2 and SDC2 in stool specimens for Colorectal Cancer early detection: A cost-effective strategy for Chinese population

Performance Comparison Between Plasma and Stool Methylated SEPT9 Tests for Detecting Colorectal Cancer

Real‐world application of a fast stool DNA test for colorectal cancer screening in primary screening positive population

Contact Info

Product

Resources

About