Implications of Intratumor Heterogeneity on Consensus Molecular Subtype (CMS) in Colorectal Cancer.
Simple Summary: Colorectal cancer (CRC) has been divided into four consensus molecular subtypes (CMS) using the unsupervised clustering of bulk transcriptomic data. The CMS, which align with known biological differences in CRC, have helped address inter-tumor heterogeneity and have been shown to be...
| Published in: | Cancers Vol. 13; no. 19; pp. 4923 - 4924 |
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| Main Authors: | , , , , , |
| Format: | research tables/charts Journal Article |
| Published: |
MDPI
Oct2021
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| Online Access: | View this record in EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=152971419&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 152971419 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 20726694 B74B jtl: Cancers issn: 20726694 maglogo: N pubinfo: dt: Oct2021 vid: 13 iid: 19 pid: 97109 pub: MDPI artinfo: ui: 152971419 152971419 152971419 10.3390/cancers13194923 152971419 ppf: 4923 ppct: 1 formats: tig: atl: Implications of Intratumor Heterogeneity on Consensus Molecular Subtype (CMS) in Colorectal Cancer. aug: au: Chowdhury, Saikat Hofree, Matan Lin, Kangyu Maru, Dipen Kopetz, Scott Shen, John Paul affil: Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA sug: subj: Colorectal Neoplasms Pathology Colorectal Neoplasms Classification Human Cytological Techniques RNA Analysis Sequence Analysis Algorithms Tumor Markers, Biological Gene Expression Immune System Connective Tissue Cells Epithelial Cells Descriptive Statistics ab: Simple Summary: Colorectal cancer (CRC) has been divided into four consensus molecular subtypes (CMS) using the unsupervised clustering of bulk transcriptomic data. The CMS, which align with known biological differences in CRC, have helped address inter-tumor heterogeneity and have been shown to be predictive of survival. However, bulk tumors are comprised of a mix of tumor cells, non-tumor stroma, and immune cells, and the relative contributions of each are not accounted for in the current CMS classification system. Here, we build an algorithm to assign CMS classification to individual cells, which we apply to single cell RNAseq data to explore the impact of intra-tumor heterogeneity on CMS. We find that the number of stromal and immune cells present has a strong influence on the bulk CMS type and that clusters of tumor epithelial cells derived from single cell RNAseq do not align with CMS. The implications of intratumor heterogeneity on the four consensus molecular subtypes (CMS) of colorectal cancer (CRC) are not well known. Here, we use single-cell RNA sequencing (scRNASeq) to build an algorithm to assign CMS classification to individual cells, which we use to explore the distributions of CMSs in tumor and non-tumor cells. A dataset of colorectal tumors with bulk RNAseq (n = 3232) was used to identify CMS specific-marker gene sets. These gene sets were then applied to a discovery dataset of scRNASeq profiles (n = 10) to develop an algorithm for single-cell CMS (scCMS) assignment, which recapitulated the intrinsic biology of all four CMSs. The single-cell CMS assignment algorithm was used to explore the scRNASeq profiles of two prospective CRC tumors with mixed CMS via bulk sequencing. We find that every CRC tumor contains individual cells of each scCMS, as well as many individual cells that have enrichment for features of more than one scCMS (called mixed cells). scCMS4 and scCMS1 cells dominate stroma and immune cell clusters, respectively, but account for less than 3% epithelial cells. These data imply that CMS1 and CMS4 are driven by the transcriptomic contribution of immune and stromal cells, respectively, not tumor cells. pubtype: Academic Journal doctype: research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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