The Consensus Molecular Subtypes of Colorectal Cancer
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This article review discusses the consensus molecular subtypes of colorectal cancer and their clinical implications. It explores the key findings of the paper and their potential for developing strategies for drug innovation and treatment of CRC tumors.
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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:
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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. Molecularcharacterizationof CMS depicts-CMS1 is hyper methylated,haslow- 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. Theyarealsoknowntobeassociatedwithangiogenesisandupregulatedmatrix 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 onpatientsubgroups,allowedforfuturediscoveryinthisfieldonthebasisof 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 thexenograft 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.
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4THE CONSENSUS MOLECULAR SUBTYPES OF COLORECTAL CANCER Reference Brunelli, L., Caiola, E., Marabese, M., Broggini, M., & Pastorelli, R. (2014). Capturing the metabolomicdiversityofKRASmutantsinnon-small-celllungcancer cells.Oncotarget,5(13), 4722. Kim, E. K., & Choi, E. J. (2015). Compromised MAPK signaling in human diseases: an update.Archives of toxicology,89(6), 867-882. Le, D. T., Uram, J. N., Wang, H., Bartlett, B. R., Kemberling, H., Eyring, A. D., ... & Biedrzycki, B. (2015). PD-1 blockade in tumors with mismatch-repair deficiency.New England Journal of Medicine,372(26), 2509-2520. Li, Y., Choi, P. S., Casey, S. C., Dill, D. L., & Felsher, D. W. (2014). MYC through miR-17-92 suppresses specific target genes to maintain survival, autonomous proliferation, and a neoplastic state.Cancer cell,26(2), 262-272. Llosa, N. J., Cruise, M., Tam, A., Wicks, E. C., Hechenbleikner, E. M., Taube, J. M., ... & Zhang, M. (2015). The vigorous immune microenvironment of microsatellite instable coloncancerisbalancedbymultiplecounter-inhibitorycheckpoints.Cancer discovery,5(1), 43-51. Son, J., Lyssiotis, C. A., Ying, H., Wang, X., Hua, S., Ligorio, M., ... & Kang, Y. A. (2013). Glutamine supports pancreatic cancer growth through a KRAS-regulated metabolic pathway.Nature,496(7443), 101.
5THE CONSENSUS MOLECULAR SUBTYPES OF COLORECTAL CANCER Yoshihara, K., Shahmoradgoli, M., Martínez, E., Vegesna, R., Kim, H., Torres-Garcia, W., ... & Carter, S. L. (2013). Inferring tumour purity and stromal and immune cell admixture from expression data.Nature communications,4, 2612.