Colorectal Cancer: A Review of Consensus Molecular Subtypes

This paper reviews the consensus molecular subtypes (CMS) of colorectal cancer, highlighting key findings from a network-based approach that classifies CRC into four core subtypes. It emphasizes that a significant portion of primary tumors doesn't fit neatly into these consensus categories. The molecular characteristics of each CMS are detailed, including hypermethylation in CMS1, chromosomal instability in CMS2-4, and KRAS mutations in CMS3. CMS1 tumors show a strong immune response, CMS2 exhibits overexpression of miR-17–92 clusters, and CMS4 is associated with epithelial-to-mesenchymal transition. Clinically, CMS1 and CMS4 have poor survival rates, while CMS2 has better outcomes. The review concludes that understanding these subtypes has implications for developing targeted therapies, such as those targeting oncogene amplification in CMS2 or TGF-β signaling in CMS4, and improving clinical trial designs and cancer cell line classification. Desklib provides access to similar solved assignments and study resources for students.

Running head: THE CONSENSUS MOLECULAR SUBTYPES OF COLORECTAL CANCER
ARTICLE REVIEW ON THE CONSENSUS MOLECULAR SUBTYPES OF COLORECTAL
CANCER
Name of Student:
Name of University:
Author’s Note:

1THE CONSENSUS MOLECULAR SUBTYPES OF COLORECTAL CANCER
1. The significant key findings of the paper are:
 Network-based approach that used 6 CRC classification system revealed four sets of core
consensus molecular subtypes.
 Out of 3962 labelled CMS subtypes used, 3104 samples were associated with tumour,
and the remaining non-consensus sample represents significant amount of primary
tumours.
 Molecular characterization of CMS depicts- CMS1 is hyper methylated, has low-
frequency SCNAs, they have overexpression of DNA repair proteins, are defective in
DNA mismatch repair, high incidence of BRAF mutation. CMS2 to CMS4 exhibited
chromosomal instability. CMS3 had overexpression of KRAS mutation.
 CMS1 tumour display high level of immune response proteins. While CMS2 tumours had
overexpression of miR-17–92 clusters and there were more copy number of oncogenes
than tumour suppressor gene. CMS3 tumour had low display of proteins of let-7 miR
family.
 CMS1 tumour is common in female showing right side lesion, and CMS2 tumour showed
left-sided lesion. CMCS4 is mostly diagnosed in later stage of cancer. Cox, proportional
hazards analysis, revealed that CMS4, CMS1 tumours had poor survival rate whereas
CMS2 had long term survival rates.
2. From the above finding of CMSs groups, colorectal cancer in human have no relation
with disruption of RTK and MAPK signalling pathway (Kim & Choi, 2015). CMS1
tumour has slow survival rate and is displayed by many molecular changes. CMS1 had
high expression of genes that is connected with diffusion of immune infiltrate and they
are mostly comprised of T helper cell and T cytotoxic cells (Llosa et al., 2015) In account

2THE CONSENSUS MOLECULAR SUBTYPES OF COLORECTAL CANCER
of that they have strongly activated pathway of immune evasion. CMS2 being associated
with high expression of miR-17–92 clusters and right-sided lesion can be depicted by its
biological functions (Li et al., 2014). CMS2 has upregulated downstream expression
WNT and MYC gene target, which is the primary reason for carcinogenesis, therefore,
CMS2 tumour show high differentiation of epithelial cells (Brunelli et al., 2014). CMS3
had high expression of KRAS mutation which is due to presence of dysregulated multiple
metabolism pathways (Son et al., 2013). CMS4 tumours can be due to over-expression of
genes of epithelial-to-mesenchymal change (EMT). They have activated transforming
growth factor-β signalling which cause abnormal division of cells, thus causing cancer.
They are also known to be associated with angiogenesis and upregulated matrix
remodelling pathways. CMS4 population has low survival rate which can be due to
defective complement-mediated inflammatory system (Yoshihara et al., 2013).
3. The clinical and therapeutic implication of the finding of subsets of colorectal tumour and
its characterization say that they have potential to develop strategies for drugs innovation
that can treat CRC tumours. MSI is known to identify the blockade of immune
checkpoint in advanced stage of CRC; therefore, this formula can be used form different
drugs related to cancer (Le et al., 2015). It was found that oncogene amplifies at the high
rate in CMS2 samples and dependence of TGF-β signalling pathway in CMS4 have the
capability to form novel therapy for CRC that can target the oncogene and TGF-β
signalling proteins. The clinical trials analysis that used semi-supervised approach based
on patient subgroups, allowed for future discovery in this field on the basis of
experimental result. The significant finding of the paper that shows CRC heterogeneity
can be the reason for development of systematic interrogation tool and it will increase the

3THE CONSENSUS MOLECULAR SUBTYPES OF COLORECTAL CANCER
dimension for classification of cell lines. It will also help in improving the xenograft
model with the availability of drug sensitive data. CMS classifier can be used as research
tool for whole community for relevant detection of type of CRC in human beings and can
make the study of molecular cancer easy and informative.

4THE CONSENSUS MOLECULAR SUBTYPES OF COLORECTAL CANCER
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