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Research article
Interconnectivity between molecular subtypes and tumor stage in colorectal cancer
Louis Vermeulen
Amsterdam Universitair Medische Centra
Corresponding Author
ORCiD: https://orcid.org/0000-0002-6066-789X
License:
This work is licensed under a CC BY 4.0 License. Read Full License
View the published version at BMC Cancer.
Background: There are profound individual differences in clinical outcomes between colorectal cancers (CRCs) presenting with identical stage of disease. Molecular stratification, in conjunction with the traditional TNM staging, is a promising way to predict patient outcomes. We investigated the interconnectivity between tumor stage and tumor biology reflected by the Consensus Molecular Subtypes (CMSs) in CRC, and explored the possible value of these insights in patients with stage II colon cancer.
Methods: We performed a retrospective analysis using clinical records and gene expression profiling in a meta-cohort of 1040 CRC patients. The interconnectivity of tumor biology and disease stage was assessed by investigating the association between CMSs and TNM classification. In order to validate the clinical applicability of our findings we employed a meta-cohort of 197 stage II colon cancers.
Results: CMS4 was significantly more prevalent in advanced stages of disease (stage I 9.8% versus stage IV 38.5%, p<0.001). The observed differential gene expression between cancer stages is at least partly explained by the biological differences as reflected by CMS subtypes. Gene signatures for stage III-IV and CMS4 were highly correlated (r=0.77, p<0.001). CMS4 cancers showed an increased progression rate to more advanced stages (CMS4 compared to CMS2: 1.25, 95% CI: 1.08-1.46). Patients with a CMS4 cancer had worse survival in the high-risk stage II tumors compared to the total stage II cohort (5-year DFS 41.7% versus 100.0%, p=0.008).
Conclusions: Considerable interconnectivity between tumor biology and tumor stage in CRC exists. This implies that the TNM stage, in addition to the stage of progression, might also reflect distinct biological disease entities. These insights can potentially be utilized to optimize identification of high-risk stage II colon cancers.
Keywords
colorectal cancer, molecular subtype, tumor biology, CMS, TNM
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CURRENT STATUS: Published
Version 2
Posted 10 Aug, 2020
Published
On 04 Sep, 2020
No community comments so far
Editorial decision: Accept
On 17 Aug, 2020
Review #2 received
Received 05 Aug, 2020
Reviewer #1 agreed
On 05 Aug, 2020
Reviewer #2 agreed
On 05 Aug, 2020
Reviewers invited
Invitations sent on 05 Aug, 2020
Review #1 received
Received 05 Aug, 2020
Editor assigned
On 02 Aug, 2020
Submission checks complete
On 01 Aug, 2020
Editor invited
On 01 Aug, 2020
No comments provided
Review #2 received
Received 24 Jul, 2020
Editorial decision: Minor revision
On 24 Jul, 2020
Reviewer #3 agreed
On 07 Jul, 2020
Review #1 received
Received 07 May, 2020
Reviewer #2 agreed
On 06 May, 2020
Reviewer #1 agreed
On 29 Apr, 2020
Reviewers invited
Invitations sent on 15 Apr, 2020
Editor assigned
On 06 Apr, 2020
Submission checks complete
On 02 Apr, 2020
Editor invited
On 02 Apr, 2020
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This preprint is under consideration at BMC Cancer. A preprint is 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
Interconnectivity between molecular subtypes and tumor stage in colorectal cancer
Louis Vermeulen
Amsterdam Universitair Medische Centra
Corresponding Author
ORCiD: https://orcid.org/0000-0002-6066-789X
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
Version 2
Posted 10 Aug, 2020
Published
On 04 Sep, 2020
No community comments so far
Editorial decision: Accept
On 17 Aug, 2020
Review #2 received
Received 05 Aug, 2020
Reviewer #1 agreed
On 05 Aug, 2020
Reviewer #2 agreed
On 05 Aug, 2020
Reviewers invited
Invitations sent on 05 Aug, 2020
Review #1 received
Received 05 Aug, 2020
Editor assigned
On 02 Aug, 2020
Submission checks complete
On 01 Aug, 2020
Editor invited
On 01 Aug, 2020
No comments provided
Review #2 received
Received 24 Jul, 2020
Editorial decision: Minor revision
On 24 Jul, 2020
Reviewer #3 agreed
On 07 Jul, 2020
Review #1 received
Received 07 May, 2020
Reviewer #2 agreed
On 06 May, 2020
Reviewer #1 agreed
On 29 Apr, 2020
Reviewers invited
Invitations sent on 15 Apr, 2020
Editor assigned
On 06 Apr, 2020
Submission checks complete
On 02 Apr, 2020
Editor invited
On 02 Apr, 2020
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
License:
This work is licensed under a CC BY 4.0 License. Read Full License
View the published version at BMC Cancer.
Background: There are profound individual differences in clinical outcomes between colorectal cancers (CRCs) presenting with identical stage of disease. Molecular stratification, in conjunction with the traditional TNM staging, is a promising way to predict patient outcomes. We investigated the interconnectivity between tumor stage and tumor biology reflected by the Consensus Molecular Subtypes (CMSs) in CRC, and explored the possible value of these insights in patients with stage II colon cancer.
Methods: We performed a retrospective analysis using clinical records and gene expression profiling in a meta-cohort of 1040 CRC patients. The interconnectivity of tumor biology and disease stage was assessed by investigating the association between CMSs and TNM classification. In order to validate the clinical applicability of our findings we employed a meta-cohort of 197 stage II colon cancers.
Results: CMS4 was significantly more prevalent in advanced stages of disease (stage I 9.8% versus stage IV 38.5%, p<0.001). The observed differential gene expression between cancer stages is at least partly explained by the biological differences as reflected by CMS subtypes. Gene signatures for stage III-IV and CMS4 were highly correlated (r=0.77, p<0.001). CMS4 cancers showed an increased progression rate to more advanced stages (CMS4 compared to CMS2: 1.25, 95% CI: 1.08-1.46). Patients with a CMS4 cancer had worse survival in the high-risk stage II tumors compared to the total stage II cohort (5-year DFS 41.7% versus 100.0%, p=0.008).
Conclusions: Considerable interconnectivity between tumor biology and tumor stage in CRC exists. This implies that the TNM stage, in addition to the stage of progression, might also reflect distinct biological disease entities. These insights can potentially be utilized to optimize identification of high-risk stage II colon cancers.
Figure 1
Figure 2
Figure 3