Unsupervised analyses reveal molecular subtypes associated to prognosis and response to therapy in colorectal cancer

2014 ◽  
Vol 3 (3) ◽  
pp. 277-288 ◽  
Author(s):  
Rebeca Sanz-Pamplona ◽  
Cristina Santos ◽  
Julieta Grasselli ◽  
David G Molleví ◽  
Rodrigo Dienstmann ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Molecular Subtypes ◽  
Response To Therapy

scholarly journals COLORECTAL MOLECULAR SUBTYPES – PROGRESS OR DEADLOCK?

2021 ◽  
Vol 22 (1) ◽  
pp. 72-86
Author(s):  
M.Yu. Fedyanin ◽  
E.O. Ignatova ◽  
А.А. Tryakin
Keyword(s):  
Colorectal Cancer ◽  
Critical Analysis ◽  
Molecular Subtypes ◽  
Molecular Genetic ◽  
Response To Therapy ◽  
Omics Data ◽  
New Era ◽  
The Past ◽  
Genetic Subtypes ◽  
Morphological Picture

Attempts to classify tumors in order to substantiate the different course of the disease and response to therapy have undergone significant changes over the past decades and have advanced from the creation of prognostic systems based on the clinical and morphological picture to the division into molecular-genetic subtypes. The latter, based on various omics data, should have opened a new era in oncology, dividing tumors not only according to the prognostic course, but also allowing individualized treatment. However, data from clinical trials, at least in colorectal cancer, show conflicting results. This review is devoted to the critical analysis of the applicability of molecular genetic subtyping of colon tumors in clinical practice.

scholarly journals YY1 Silencing Induces 5-Fluorouracil-Resistance and BCL2L15 Downregulation in Colorectal Cancer Cells: Diagnostic and Prognostic Relevance

2021 ◽  
Vol 22 (16) ◽  
pp. 8481
Author(s):  
Silvia Vivarelli ◽  
Luca Falzone ◽  
Saverio Candido ◽  
Benjamin Bonavida ◽  
Massimo Libra
Keyword(s):  
Colorectal Cancer ◽  
Response To Therapy ◽  
Advanced Stage ◽  
Relapse Free Survival ◽  
Free Survival ◽  
Expression Levels ◽  
Single Cell Sequencing ◽  
Yin Yang 1 ◽  
Anti Cancer ◽  
Colorectal Cancer Cells

Colorectal cancer (CRC) is characterized by genetic heterogeneity and is often diagnosed at an advanced stage. Therefore, there is a need to identify novel predictive markers. Yin Yang 1 (YY1) is a transcription factor playing a dual role in cancer. The present study aimed to investigate whether YY1 expression levels influence CRC cell response to therapy and to identify the transcriptional targets involved. The diagnostic and prognostic values of YY1 and the identified factor(s) in CRC patients were also explored. Silencing of YY1 increased the resistance to 5-Fluorouracil-induced cytotoxicity in two out of four CRC cells with different genotypes. BCL2L15/Bfk pro-apoptotic factor was found selectively expressed in the responder CRC cells and downregulated upon YY1 knockdown. CRC dataset analyses corroborated a tumor-suppressive role for both YY1 and BCL2L15 whose expressions were inversely correlated with aggressiveness. CRC single-cell sequencing dataset analyses demonstrated higher co-expression levels of both YY1 and BCL2L15 within defined tumor cell clusters. Finally, elevated levels of YY1 and BCL2L15 in CRC patients were associated with larger relapse-free survival. Given their observed anti-cancer role, we propose YY1 and BCL2L15 as candidate diagnostic and prognostic CRC biomarkers.

scholarly journals Metastatic heterogeneity of the consensus molecular subtypes of colorectal cancer

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Peter W. Eide ◽  
Seyed H. Moosavi ◽  
Ina A. Eilertsen ◽  
Tuva H. Brunsell ◽  
Jonas Langerud ◽  
...  
Keyword(s):  
Gene Expression ◽  
Colorectal Cancer ◽  
Principal Components ◽  
Prognostic Value ◽  
Tumor Heterogeneity ◽  
Molecular Subtypes ◽  
R Package ◽  
Data Set ◽  
Primary Tumors ◽  
External Data

AbstractGene expression-based subtypes of colorectal cancer have clinical relevance, but the representativeness of primary tumors and the consensus molecular subtypes (CMS) for metastatic cancers is not well known. We investigated the metastatic heterogeneity of CMS. The best approach to subtype translation was delineated by comparisons of transcriptomic profiles from 317 primary tumors and 295 liver metastases, including multi-metastatic samples from 45 patients and 14 primary-metastasis sets. Associations were validated in an external data set (n = 618). Projection of metastases onto principal components of primary tumors showed that metastases were depleted of CMS1-immune/CMS3-metabolic signals, enriched for CMS4-mesenchymal/stromal signals, and heavily influenced by the microenvironment. The tailored CMS classifier (available in an updated version of the R package CMScaller) therefore implemented an approach to regress out the liver tissue background. The majority of classified metastases were either CMS2 or CMS4. Nonetheless, subtype switching and inter-metastatic CMS heterogeneity were frequent and increased with sampling intensity. Poor-prognostic value of CMS1/3 metastases was consistent in the context of intra-patient tumor heterogeneity.

Consensus molecular subtypes in metastatic colorectal cancer treated with sequential versus combined fluoropyrimidine, bevacizumab and irinotecan (XELAVIRI trial)

2021 ◽  
Vol 157 ◽  
pp. 71-80
Author(s):  
Arndt Stahler ◽  
Volker Heinemann ◽  
Veronika Schuster ◽  
Kathrin Heinrich ◽  
Annika Kurreck ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Molecular Subtypes

Classification of Colorectal Cancer in Molecular Subtypes by Immunohistochemistry

2018 ◽  
pp. 179-191 ◽  
Author(s):  
Sanne ten Hoorn ◽  
Anne Trinh ◽  
Joan de Jong ◽  
Lianne Koens ◽  
Louis Vermeulen
Keyword(s):  
Colorectal Cancer ◽  
Molecular Subtypes

A panel of DNA methylation markers for the classification of consensus molecular subtypes 2 and 3 in patients with colorectal cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 3545-3545
Author(s):  
Inge van Den Berg ◽  
Marcel Smid ◽  
Robert R.J. Coebergh van den Braak ◽  
Mark A van de Wiel ◽  
Carolien H. M. Van Deurzen ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Dna Methylation ◽  
Prediction Models ◽  
Molecular Subtypes ◽  
Cpg Island ◽  
Methylation Marker ◽  
Marker Selection ◽  
Fresh Frozen ◽  
Classification Tool

3545 Background: Consensus molecular subtypes (CMSs) can guide precision treatment of colorectal cancer (CRC). Currently available assays can identify CMS1 and CMS4 cases well, while a dedicated test to distinguish CMS2 and 3 is lacking. This study aimed to identify a panel of methylation markers to distinguish between CMS2 and 3 in patients with CRC. Methods: Fresh-frozen tumor tissue of 239 patients with stage I-III CRC was included. CMS classification was performed on RNA-seq data using the single-sample-prediction parameter from the “CMSclassifier” package. Methylation profiles were obtained using the Infinium HumanMethylation450 BeadChip. We performed adaptive group-regularised logistic ridge-regression with post-hoc group-weighted elastic net marker selection to build prediction models for classification of CMS2 and CMS3 based on 15, 10 or 5 markers. Data from TCGAwas used for validation. Results: Overall methylation profiles differed between CMS2 and CMS3. Group-regularisation of the probes was done based on their location either relative to a CpG island or relative to a gene present in the CMS classifier resulting in two different prediction models and subsequently different marker panels. For both panels, even when using only 5 markers, sensitivity, specificity, and accuracy were > 90%. Validation showed comparable performances. Conclusions: Our highly sensitive and specific methylation marker panel can be used to distinguish CMS2 and 3. This enables development of a qPCR DNA methylation assay in patients with CRC to provide a specific and non-invasive classification tool.

scholarly journals YAP/TAZ Signalling in Colorectal Cancer: Lessons from Consensus Molecular Subtypes

Cancers ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3160
Author(s):  
Sophie Mouillet-Richard ◽  
Pierre Laurent-Puig
Keyword(s):  
Colorectal Cancer ◽  
Cancer Progression ◽  
Molecular Subtypes ◽  
Hippo Pathway ◽  
Molecular Classification ◽  
Colorectal Cancer Progression ◽  
Definition Of ◽  
The Hippo Pathway ◽  
Future Work

Recent advance in the characterization of the heterogeneity of colorectal cancer has led to the definition of a consensus molecular classification within four CMS subgroups, each associated with specific molecular and clinical features. Investigating the signalling pathways that drive colorectal cancer progression in relation to the CMS classification may help design therapeutic strategies tailored for each CMS subtype. The two main effectors of the Hippo pathway YAP and its paralogue TAZ have been intensively scrutinized for their contribution to colon carcinogenesis. Here, we review the knowledge of YAP/TAZ implication in colorectal cancer from the perspective of the CMS framework. We identify gaps in our current understanding and delineate research avenues for future work.

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