Improved Delineation of Colorectal Cancer Molecular Subtypes and Functional Profiles with a 62-Gene Panel
Issued Date
2023-03-01
Resource Type
eISSN
15573125
Scopus ID
2-s2.0-85149154397
Pubmed ID
36490322
Journal Title
Molecular cancer research : MCR
Volume
21
Issue
3
Start Page
240
End Page
252
Rights Holder(s)
SCOPUS
Bibliographic Citation
Molecular cancer research : MCR Vol.21 No.3 (2023) , 240-252
Suggested Citation
Bhukdee D., Nuwongsri P., Israsena N., Sriswasdi S. Improved Delineation of Colorectal Cancer Molecular Subtypes and Functional Profiles with a 62-Gene Panel. Molecular cancer research : MCR Vol.21 No.3 (2023) , 240-252. 252. doi:10.1158/1541-7786.MCR-22-0476 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/81640
Title
Improved Delineation of Colorectal Cancer Molecular Subtypes and Functional Profiles with a 62-Gene Panel
Author(s)
Author's Affiliation
Other Contributor(s)
Abstract
Since its establishment in 2015, the transcriptomics-based consensus molecular subtype (CMS) classification has unified our understanding of colorectal cancer. Each of the four CMS exhibited distinctive high-level molecular signatures that correlated well with prognosis and treatment response. Nonetheless, many key aspects of colorectal cancer progression and intra-subtype heterogeneity remain unresolved. This is partly because the bulk transcriptomic data used to define CMS contain substantial interference from non-tumor cells. Here, we propose a concise panel of 62 genes that not only accurately recapitulates all key characteristics of the four original CMS but also identifies three additional subpopulations with unique molecular signatures. Validation on independent cohorts confirms that the new CMS4 intra-subtypes coincide with single-cell-derived intrinsic subtypes and that the panel consists of many immune cell-type markers that can capture the status of tumor microenvironment. Furthermore, a 2D embedding of CMS structure based on the proposed gene panel provides a high-resolution view of the functional pathways and cell-type markers that underlie each CMS intra-subtype and the continuous progression from CMS2 to CMS4 subtypes. Our gene panel and 2D visualization refined the delineation of colorectal cancer subtypes and could aid further discovery of molecular mechanisms in colorectal cancer. IMPLICATIONS: : Well-selected gene panel and representation can capture both the continuum of cancer cell states and tumor microenvironment status.