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Research article
Yashuang Zhao
Harbin Medical University
Corresponding Author
ORCiD: https://orcid.org/0000-0002-7425-5773
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Background Differential DNA methylation panel derived from peripheral blood could serve as biomarkers of CRC susceptibility. However, most of the previous studies utilized post-diagnostic blood DNA which may be markers of disease rather than susceptibility. In addition, to date no study has evaluated the predictive potential of such markers in a prospective cohort and on a genome-wide basis. The aim of this study was to identify potential panel of DNA methylation biomarkers in peripheral blood that are associated with CRC risk and therefore serve as epigenetic biomarkers of disease susceptibility.
Methods DNA methylation profile of a nested case-control study with 166 CRC and 424 healthy normal subjects were obtained from Gene Expression Omnibus (GEO) database. The differentially methylated markers were identified by moderated t-statistics. The DNA methylation panel were constructed by stepwise logistic regression and least absolute shrinkage and selection operator in training dataset. A methylation risk score (MRS) model was constructed and the association between MRS and CRC risk assessed.
Results We identified 48 differentially methylated CpGs sites, of which 33 were hypomethylated. Of these, sixteen-CpG based MRS that was associated with CRC risk (OR = 2.68, 95% CI: 2.13, 3.38, P < 0.0001) was constructed. This association is confirmed in the testing dataset (OR = 2.02, 95% CI: 1.48, 2.74, P < 0.0001) and persisted in both males and females, younger and older subjects, short and long time-to-diagnosis. The MRS also predicted CRC with AUC 0.82 (95% CI: 0.76, 0.88), indicating high accuracy.
Conclusions Our study has identified a novel DNA methylation panel that is associated with CRC and could be-useful for the prediction of CRC risk in the future.
Keywords
Colorectal cancer, DNA methylation, methylation risk score, peripheral blood
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CURRENT STATUS: Published
View the published article at BMC Cancer.
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Review #1 received
Received 03 Jul, 2020
Reviewer #1 agreed
On 11 Jun, 2020
Reviewers invited
Invitations sent on 08 Jun, 2020
Editor assigned
On 27 May, 2020
Submission checks complete
On 26 May, 2020
Editor invited
On 26 May, 2020
Version 1
Posted 24 Feb, 2020
No comments provided
Editorial decision: Major revision
On 28 Apr, 2020
Review #4 received
Received 09 Apr, 2020
Review #3 received
Received 09 Apr, 2020
Review #1 received
Received 05 Apr, 2020
Review #2 received
Received 05 Apr, 2020
Reviewer #4 agreed
On 29 Mar, 2020
Reviewer #2 agreed
On 28 Mar, 2020
Reviewer #3 agreed
On 28 Mar, 2020
Reviewer #1 agreed
On 16 Mar, 2020
Reviewers invited
Invitations sent on 01 Mar, 2020
Editor assigned
On 14 Feb, 2020
Submission checks complete
On 13 Feb, 2020
Editor invited
On 13 Feb, 2020
First submitted
On 12 Feb, 2020
Metrics
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Subject Areas
Oncology
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See the published version of this preprint at BMC Cancer.
This is a preprint, a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research article
Yashuang Zhao
Harbin Medical University
Corresponding Author
ORCiD: https://orcid.org/0000-0002-7425-5773
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Published
View the published article at BMC Cancer.
No community comments so far
Review #1 received
Received 03 Jul, 2020
Reviewer #1 agreed
On 11 Jun, 2020
Reviewers invited
Invitations sent on 08 Jun, 2020
Editor assigned
On 27 May, 2020
Submission checks complete
On 26 May, 2020
Editor invited
On 26 May, 2020
Version 1
Posted 24 Feb, 2020
No comments provided
Editorial decision: Major revision
On 28 Apr, 2020
Review #4 received
Received 09 Apr, 2020
Review #3 received
Received 09 Apr, 2020
Review #1 received
Received 05 Apr, 2020
Review #2 received
Received 05 Apr, 2020
Reviewer #4 agreed
On 29 Mar, 2020
Reviewer #2 agreed
On 28 Mar, 2020
Reviewer #3 agreed
On 28 Mar, 2020
Reviewer #1 agreed
On 16 Mar, 2020
Reviewers invited
Invitations sent on 01 Mar, 2020
Editor assigned
On 14 Feb, 2020
Submission checks complete
On 13 Feb, 2020
Editor invited
On 13 Feb, 2020
First submitted
On 12 Feb, 2020
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Oncology
License:
This work is licensed under a CC BY 4.0 License. Read Full License
View the published article at BMC Cancer.
Background Differential DNA methylation panel derived from peripheral blood could serve as biomarkers of CRC susceptibility. However, most of the previous studies utilized post-diagnostic blood DNA which may be markers of disease rather than susceptibility. In addition, to date no study has evaluated the predictive potential of such markers in a prospective cohort and on a genome-wide basis. The aim of this study was to identify potential panel of DNA methylation biomarkers in peripheral blood that are associated with CRC risk and therefore serve as epigenetic biomarkers of disease susceptibility.
Methods DNA methylation profile of a nested case-control study with 166 CRC and 424 healthy normal subjects were obtained from Gene Expression Omnibus (GEO) database. The differentially methylated markers were identified by moderated t-statistics. The DNA methylation panel were constructed by stepwise logistic regression and least absolute shrinkage and selection operator in training dataset. A methylation risk score (MRS) model was constructed and the association between MRS and CRC risk assessed.
Results We identified 48 differentially methylated CpGs sites, of which 33 were hypomethylated. Of these, sixteen-CpG based MRS that was associated with CRC risk (OR = 2.68, 95% CI: 2.13, 3.38, P < 0.0001) was constructed. This association is confirmed in the testing dataset (OR = 2.02, 95% CI: 1.48, 2.74, P < 0.0001) and persisted in both males and females, younger and older subjects, short and long time-to-diagnosis. The MRS also predicted CRC with AUC 0.82 (95% CI: 0.76, 0.88), indicating high accuracy.
Conclusions Our study has identified a novel DNA methylation panel that is associated with CRC and could be-useful for the prediction of CRC risk in the future.
Figure 1
Figure 2
Figure 3
This is a list of supplementary files associated with this preprint. Click to download.
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