小柯机器人

新加坡基因组研究所Iain Beehuat Tan等研究人员合作利用单细胞和大量转录组测序，确定了两种上皮性肿瘤细胞状态并完善了结直肠癌的共识分子分类。2022年6月30日，国际知名学术期刊《自然—遗传学》在线发表了这一成果。

研究人员表示，结直肠癌的共识分子亚型（CMS）分类是基于大量转录组学。潜在的上皮细胞多样性仍然不清楚。

研究人员分析了63名患者的373,058个单细胞转录组，重点是49,155个上皮细胞。研究人员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。研究人员在3,614名患者的大宗转录组中再现了这些亚型。iCMS2和iCMS3这两种内在亚型完善了CMS。iCMS3包括微卫星不稳定（MSI-H）的癌症和三分之一的微卫星稳定（MSS）的肿瘤。iCMS3 MSS癌症在转录组上与MSI-H癌症比与其他MSS癌症更相似。CMS4癌症有iCMS2或iCMS3上皮细胞；后者的预后最差。

研究人员定义了结直肠癌的内在上皮轴，并提出了一个精细的"IMF"分类，包括五个亚型，将内在上皮亚型（I）、微卫星不稳定状态（M）和纤维化（F）结合起来。

附：英文原文

Title: Single-cell and bulk transcriptome sequencing identifies two epithelial tumor cell states and refines the consensus molecular classification of colorectal cancer

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

Issue&Volume: 2022-06-30

Abstract: 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).

DOI: 10.1038/s41588-022-01100-4

Source: https://www.nature.com/articles/s41588-022-01100-4

Nature Genetics：《自然—遗传学》，创刊于1992年。隶属于施普林格·自然出版集团，最新IF：41.307
官方网址：https://www.nature.com/ng/
投稿链接：https://mts-ng.nature.com/cgi-bin/main.plex