Implications of Intratumor Heterogeneity on Consensus Molecular Subtype (CMS) in Colorectal Cancer

Cancers

Scott Kopetz¹  Kangyu Lin¹  John Paul Shen¹  Saikat Chowdhury¹  Dipen Maru²  Matan Hofree³ 

[1] Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA;Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA;Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA;

关键词: colorectal cancer;    consensus molecular subtypes (CMS);    single-cell sequencing;    RNAseq;    intratumor heterogeneity;   

DOI  :  10.3390/cancers13194923

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown