Implications of Intratumor Heterogeneity on Consensus Molecular Subtype (CMS) in Colorectal Cancer
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 distributi...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-09-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/13/19/4923 |
| _version_ | 1797516741173051392 |
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| author | Saikat Chowdhury Matan Hofree Kangyu Lin Dipen Maru Scott Kopetz John Paul Shen |
| author_facet | Saikat Chowdhury Matan Hofree Kangyu Lin Dipen Maru Scott Kopetz John Paul Shen |
| author_sort | Saikat Chowdhury |
| collection | DOAJ |
| description | 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 (<i>n</i> = 3232) was used to identify CMS specific-marker gene sets. These gene sets were then applied to a discovery dataset of scRNASeq profiles (<i>n</i> = 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. |
| first_indexed | 2024-03-10T07:05:05Z |
| format | Article |
| id | doaj.art-b49b976261864218a23817c0cb66384e |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T07:05:05Z |
| publishDate | 2021-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-b49b976261864218a23817c0cb66384e2023-11-22T15:54:23ZengMDPI AGCancers2072-66942021-09-011319492310.3390/cancers13194923Implications of Intratumor Heterogeneity on Consensus Molecular Subtype (CMS) in Colorectal CancerSaikat Chowdhury0Matan Hofree1Kangyu Lin2Dipen Maru3Scott Kopetz4John Paul Shen5Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USAKlarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USADepartment of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USADepartment of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USADepartment of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USADepartment of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USAThe 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 (<i>n</i> = 3232) was used to identify CMS specific-marker gene sets. These gene sets were then applied to a discovery dataset of scRNASeq profiles (<i>n</i> = 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.https://www.mdpi.com/2072-6694/13/19/4923colorectal cancerconsensus molecular subtypes (CMS)single-cell sequencingRNAseqintratumor heterogeneity |
| spellingShingle | Saikat Chowdhury Matan Hofree Kangyu Lin Dipen Maru Scott Kopetz John Paul Shen Implications of Intratumor Heterogeneity on Consensus Molecular Subtype (CMS) in Colorectal Cancer Cancers colorectal cancer consensus molecular subtypes (CMS) single-cell sequencing RNAseq intratumor heterogeneity |
| title | Implications of Intratumor Heterogeneity on Consensus Molecular Subtype (CMS) in Colorectal Cancer |
| title_full | Implications of Intratumor Heterogeneity on Consensus Molecular Subtype (CMS) in Colorectal Cancer |
| title_fullStr | Implications of Intratumor Heterogeneity on Consensus Molecular Subtype (CMS) in Colorectal Cancer |
| title_full_unstemmed | Implications of Intratumor Heterogeneity on Consensus Molecular Subtype (CMS) in Colorectal Cancer |
| title_short | Implications of Intratumor Heterogeneity on Consensus Molecular Subtype (CMS) in Colorectal Cancer |
| title_sort | implications of intratumor heterogeneity on consensus molecular subtype cms in colorectal cancer |
| topic | colorectal cancer consensus molecular subtypes (CMS) single-cell sequencing RNAseq intratumor heterogeneity |
| url | https://www.mdpi.com/2072-6694/13/19/4923 |
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