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Single-cell and bulk transcriptome sequencing identifies two epithelial tumor cell states and refines the consensus molecular classification of colorectal cancer
The consensus molecular subtype (CMS) classification of colorectal cancer is based on bulk transcriptomics. The underlying epithelial cell diversity remains unclear. We analyzed 373,058 single-cell transcriptomes from 63 patients, focusing on 49,155 epithelial cells. We identified a pervasive geneti...
| Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Formato: | Online Artículo Texto |
| Lenguaje: | English |
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Nature Publishing Group US
2022
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| Materias: | |
| Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9279158/ https://www.ncbi.nlm.nih.gov/pubmed/35773407 http://dx.doi.org/10.1038/s41588-022-01100-4 |
| _version_ | 1784746334360698880 |
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| author | Joanito, Ignasius Wirapati, Pratyaksha Zhao, Nancy Nawaz, Zahid Yeo, Grace Lee, Fiona Eng, Christine L. P. Macalinao, Dominique Camat Kahraman, Merve Srinivasan, Harini Lakshmanan, Vairavan Verbandt, Sara Tsantoulis, Petros Gunn, Nicole Venkatesh, Prasanna Nori Poh, Zhong Wee Nahar, Rahul Oh, Hsueh Ling Janice Loo, Jia Min Chia, Shumei Cheow, Lih Feng Cheruba, Elsie Wong, Michael Thomas Kua, Lindsay Chua, Clarinda Nguyen, Andy Golovan, Justin Gan, Anna Lim, Wan-Jun Guo, Yu Amanda Yap, Choon Kong Tay, Brenda Hong, Yourae Chong, Dawn Qingqing Chok, Aik-Yong Park, Woong-Yang Han, Shuting Chang, Mei Huan Seow-En, Isaac Fu, Cherylin Mathew, Ronnie Toh, Ee-Lin Hong, Lewis Z. Skanderup, Anders Jacobsen DasGupta, Ramanuj Ong, Chin-Ann Johnny Lim, Kiat Hon Tan, Emile K. W. Koo, Si-Lin Leow, Wei Qiang Tejpar, Sabine Prabhakar, Shyam Tan, Iain Beehuat |
| author_facet | Joanito, Ignasius Wirapati, Pratyaksha Zhao, Nancy Nawaz, Zahid Yeo, Grace Lee, Fiona Eng, Christine L. P. Macalinao, Dominique Camat Kahraman, Merve Srinivasan, Harini Lakshmanan, Vairavan Verbandt, Sara Tsantoulis, Petros Gunn, Nicole Venkatesh, Prasanna Nori Poh, Zhong Wee Nahar, Rahul Oh, Hsueh Ling Janice Loo, Jia Min Chia, Shumei Cheow, Lih Feng Cheruba, Elsie Wong, Michael Thomas Kua, Lindsay Chua, Clarinda Nguyen, Andy Golovan, Justin Gan, Anna Lim, Wan-Jun Guo, Yu Amanda Yap, Choon Kong Tay, Brenda Hong, Yourae Chong, Dawn Qingqing Chok, Aik-Yong Park, Woong-Yang Han, Shuting Chang, Mei Huan Seow-En, Isaac Fu, Cherylin Mathew, Ronnie Toh, Ee-Lin Hong, Lewis Z. Skanderup, Anders Jacobsen DasGupta, Ramanuj Ong, Chin-Ann Johnny Lim, Kiat Hon Tan, Emile K. W. Koo, Si-Lin Leow, Wei Qiang Tejpar, Sabine Prabhakar, Shyam Tan, Iain Beehuat |
| author_sort | Joanito, Ignasius |
| collection | PubMed |
| description | The consensus molecular subtype (CMS) classification of colorectal cancer is based on bulk transcriptomics. The underlying epithelial cell diversity remains unclear. We analyzed 373,058 single-cell transcriptomes from 63 patients, focusing on 49,155 epithelial cells. We identified a pervasive genetic and transcriptomic dichotomy of malignant cells, based on distinct gene expression, DNA copy number and gene regulatory network. We recapitulated these subtypes in bulk transcriptomes from 3,614 patients. The two intrinsic subtypes, iCMS2 and iCMS3, refine CMS. iCMS3 comprises microsatellite unstable (MSI-H) cancers and one-third of microsatellite-stable (MSS) tumors. iCMS3 MSS cancers are transcriptomically more similar to MSI-H cancers than to other MSS cancers. CMS4 cancers had either iCMS2 or iCMS3 epithelium; the latter had the worst prognosis. We defined the intrinsic epithelial axis of colorectal cancer and propose a refined ‘IMF’ classification with five subtypes, combining intrinsic epithelial subtype (I), microsatellite instability status (M) and fibrosis (F). |
| format | Online Article Text |
| id | pubmed-9279158 |
| institution | National Center for Biotechnology Information |
| language | English |
| publishDate | 2022 |
| publisher | Nature Publishing Group US |
| record_format | MEDLINE/PubMed |
| spelling | pubmed-92791582022-07-15 Single-cell and bulk transcriptome sequencing identifies two epithelial tumor cell states and refines the consensus molecular classification of colorectal cancer Joanito, Ignasius Wirapati, Pratyaksha Zhao, Nancy Nawaz, Zahid Yeo, Grace Lee, Fiona Eng, Christine L. P. Macalinao, Dominique Camat Kahraman, Merve Srinivasan, Harini Lakshmanan, Vairavan Verbandt, Sara Tsantoulis, Petros Gunn, Nicole Venkatesh, Prasanna Nori Poh, Zhong Wee Nahar, Rahul Oh, Hsueh Ling Janice Loo, Jia Min Chia, Shumei Cheow, Lih Feng Cheruba, Elsie Wong, Michael Thomas Kua, Lindsay Chua, Clarinda Nguyen, Andy Golovan, Justin Gan, Anna Lim, Wan-Jun Guo, Yu Amanda Yap, Choon Kong Tay, Brenda Hong, Yourae Chong, Dawn Qingqing Chok, Aik-Yong Park, Woong-Yang Han, Shuting Chang, Mei Huan Seow-En, Isaac Fu, Cherylin Mathew, Ronnie Toh, Ee-Lin Hong, Lewis Z. Skanderup, Anders Jacobsen DasGupta, Ramanuj Ong, Chin-Ann Johnny Lim, Kiat Hon Tan, Emile K. W. Koo, Si-Lin Leow, Wei Qiang Tejpar, Sabine Prabhakar, Shyam Tan, Iain Beehuat Nat Genet Article The consensus molecular subtype (CMS) classification of colorectal cancer is based on bulk transcriptomics. The underlying epithelial cell diversity remains unclear. We analyzed 373,058 single-cell transcriptomes from 63 patients, focusing on 49,155 epithelial cells. We identified a pervasive genetic and transcriptomic dichotomy of malignant cells, based on distinct gene expression, DNA copy number and gene regulatory network. We recapitulated these subtypes in bulk transcriptomes from 3,614 patients. The two intrinsic subtypes, iCMS2 and iCMS3, refine CMS. iCMS3 comprises microsatellite unstable (MSI-H) cancers and one-third of microsatellite-stable (MSS) tumors. iCMS3 MSS cancers are transcriptomically more similar to MSI-H cancers than to other MSS cancers. CMS4 cancers had either iCMS2 or iCMS3 epithelium; the latter had the worst prognosis. We defined the intrinsic epithelial axis of colorectal cancer and propose a refined ‘IMF’ classification with five subtypes, combining intrinsic epithelial subtype (I), microsatellite instability status (M) and fibrosis (F). Nature Publishing Group US 2022-06-30 2022 /pmc/articles/PMC9279158/ /pubmed/35773407 http://dx.doi.org/10.1038/s41588-022-01100-4 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
| spellingShingle | Article Joanito, Ignasius Wirapati, Pratyaksha Zhao, Nancy Nawaz, Zahid Yeo, Grace Lee, Fiona Eng, Christine L. P. Macalinao, Dominique Camat Kahraman, Merve Srinivasan, Harini Lakshmanan, Vairavan Verbandt, Sara Tsantoulis, Petros Gunn, Nicole Venkatesh, Prasanna Nori Poh, Zhong Wee Nahar, Rahul Oh, Hsueh Ling Janice Loo, Jia Min Chia, Shumei Cheow, Lih Feng Cheruba, Elsie Wong, Michael Thomas Kua, Lindsay Chua, Clarinda Nguyen, Andy Golovan, Justin Gan, Anna Lim, Wan-Jun Guo, Yu Amanda Yap, Choon Kong Tay, Brenda Hong, Yourae Chong, Dawn Qingqing Chok, Aik-Yong Park, Woong-Yang Han, Shuting Chang, Mei Huan Seow-En, Isaac Fu, Cherylin Mathew, Ronnie Toh, Ee-Lin Hong, Lewis Z. Skanderup, Anders Jacobsen DasGupta, Ramanuj Ong, Chin-Ann Johnny Lim, Kiat Hon Tan, Emile K. W. Koo, Si-Lin Leow, Wei Qiang Tejpar, Sabine Prabhakar, Shyam Tan, Iain Beehuat Single-cell and bulk transcriptome sequencing identifies two epithelial tumor cell states and refines the consensus molecular classification of colorectal cancer |
| title | Single-cell and bulk transcriptome sequencing identifies two epithelial tumor cell states and refines the consensus molecular classification of colorectal cancer |
| title_full | Single-cell and bulk transcriptome sequencing identifies two epithelial tumor cell states and refines the consensus molecular classification of colorectal cancer |
| title_fullStr | Single-cell and bulk transcriptome sequencing identifies two epithelial tumor cell states and refines the consensus molecular classification of colorectal cancer |
| title_full_unstemmed | Single-cell and bulk transcriptome sequencing identifies two epithelial tumor cell states and refines the consensus molecular classification of colorectal cancer |
| title_short | Single-cell and bulk transcriptome sequencing identifies two epithelial tumor cell states and refines the consensus molecular classification of colorectal cancer |
| title_sort | single-cell and bulk transcriptome sequencing identifies two epithelial tumor cell states and refines the consensus molecular classification of colorectal cancer |
| topic | Article |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9279158/ https://www.ncbi.nlm.nih.gov/pubmed/35773407 http://dx.doi.org/10.1038/s41588-022-01100-4 |
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