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Pharma Tech Outlook | Friday, April 08, 2022
A team of clinician-scientists and scientists, used single-cell techniques to uncover a central dichotomy for colorectal cancer cells, leading to a proposed update of the classification system for the disease.
FREMONT, CA: Colorectal cancer is one of the most prevalent malignancies and the second-leading cause of cancer-related death both in Singapore and globally. The biology of each patient's condition must be taken into account when prescribing tailored treatment for colorectal cancer patients because it is a diverse disease with significant biological and clinical variances among patients. The most reliable and extensively used transcriptomic classification system to date, colorectal cancer was categorised a couple of years ago by doctors and researchers using genes expressed by the tumour. This categorization was based on colorectal cancer subtypes. The CMS classification, however, was based on a transcriptome examination of the entire tumour, which made it unable to discern between the unique characteristics of cancer cells and other stromal cells. The research team, which was led by NCCS and GIS, examined 373,000 single cells from 141 tumour samples obtained from 63 individuals with colorectal cancer in Singapore, Belgium, and South Korea. A central dichotomy that cut across earlier classifications of colorectal cancer was discovered by the team using single-cell and bulk transcriptomics. They discovered that the malignant cells belong to two major epithelial subtypes, which they have named intrinsic-consensus molecular subtypes (iCMS), consisting of iCMS2 and iCMS3. Each subtype is distinguished by unique molecular signalling cascades, DNA duplication or deletion patterns, important gene mutation patterns, patterns of RNA abundance, and gene regulatory networks.
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The research team discovered that the iCMS3 subtype was present in one-third of MSS tumours, and these tumours included cancer cells that were substantially more comparable to MSI malignancies than other MSS cancers. Understanding the similarities between iCMS3 MSS cancers and MSI-H cancers may help researchers identify elements that can be used to adapt and adjust immunotherapy regimens, which may be most effective in patients with these tumours' biology that is comparable to MSI-H cancers. On the other hand, by comprehending the unique biology of iCMS2 MSS tumours, tailored medication development for this subset of colorectal cancer may be possible. Additionally, the iCMS2 and iCMS3 subtypes of the CMS4 group of colorectal tumours, which are known to have the highest propensity to metastasis, were equally distributed. The CMS4 tumours with iCMS3 epithelial cells were discovered to have the worse prognosis among these two groups. The research team suggested a revision to the CMS classification system known as IMF based on their findings. This system divides colorectal cancer into five groups based on the epithelial status, microsatellite status, and presence of fibrosis. The suggested IMF classification sheds fresh light on the development, progression, and therapeutic response of colorectal cancer. Additional pre-clinical and clinical research into the biology of the five groups may help with treatment, diagnosis, and prevention.
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