Genome Institute of Singapore, Agency for Science, Technology and Research (A*STAR), Singapore, Singapore.
Bioinformatics Core Facility, Swiss Institute of Bioinformatics, Lausanne, Switzerland.
Nat Genet. 2022 Jul;54(7):963-975. doi: 10.1038/s41588-022-01100-4. Epub 2022 Jun 30.
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).
结直肠癌的共识分子亚型（CMS）分类基于批量转录组学。潜在的上皮细胞多样性仍不清楚。我们分析了来自 63 名患者的 373,058 个单细胞转录组，重点关注 49,155 个上皮细胞。我们根据不同的基因表达、DNA 拷贝数和基因调控网络，确定了恶性细胞普遍存在的遗传和转录组二分法。我们在来自 3,614 名患者的批量转录组中重现了这些亚型。两个内在亚型，iCMS2 和 iCMS3，细化了 CMS。iCMS3 包括微卫星不稳定（MSI-H）癌症和三分之一的微卫星稳定（MSS）肿瘤。iCMS3 MSS 癌症在转录上与 MSI-H 癌症比与其他 MSS 癌症更相似。CMS4 癌症要么有 iCMS2，要么有 iCMS3 上皮；后者预后最差。我们定义了结直肠癌的内在上皮轴，并提出了一个经过改进的“IMF”分类，有五个亚型，包括内在上皮亚型（I）、微卫星不稳定性状态（M）和纤维化（F）。
