Single-cell and bulk transcriptome sequencing identifies two epithelial tumor cell states and refines the consensus molecular classification of colorectal cancer.
Single-cell and bulk transcriptome sequencing identifies two epithelial tumor cell states and refines the consensus molecular classification of colorectal cancer.
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单细胞和大量转录组测序鉴定了两种上皮肿瘤细胞状态，并完善了结直肠癌的共识分子分类。
DOI：
10.1038/s41588-022-01100-4
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发表时间：
2022-07
期刊：
影响因子：
30.8
通讯作者：
Tan, Iain Beehuat
中科院分区：
文献类型：
--
作者：
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
结直肠癌的一致分子亚型（CMS）分类是基于大量转录组学。潜在的上皮细胞多样性尚不清楚。我们分析了来自63名患者的373058个单细胞转录组，重点分析了49155个上皮细胞。基于不同的基因表达、DNA拷贝数和基因调控网络，我们发现了恶性细胞普遍存在的遗传和转录组二分法。我们从3,614名患者的大量转录组中总结了这些亚型。iCMS2和iCMS3这两个内在亚型完善了CMS。iCMS3包括微卫星不稳定（MSI-H）肿瘤和三分之一的微卫星稳定（MSS）肿瘤。与其他MSS癌症相比，iCMS3 MSS癌症在转录组学上与MSI-H癌症更相似。CMS4癌有iCMS2或iCMS3上皮；后者预后最差。我们定义了结直肠癌的固有上皮轴，并提出了一种细化的“IMF”分类，分为五种亚型，结合了固有上皮亚型(I)、微卫星不稳定状态(M)和纤维化(F)。63例结直肠癌患者的单细胞转录组学分析将肿瘤细胞分为两种上皮亚型。基于上皮亚型、微卫星稳定性和纤维化的改进肿瘤分类揭示了通路激活和转移的差异。
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). A single-cell transcriptomic analysis of 63 patients with colorectal cancer classifies tumor cells into two epithelial subtypes. An improved tumor classification based on epithelial subtype, microsatellite stability and fibrosis reveals differences in pathway activation and metastasis.
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影响因子：
28.2
作者：
Grasso CS;Giannakis M;Wells DK;Hamada T;Mu XJ;Quist M;Nowak JA;Nishihara R;Qian ZR;Inamura K;Morikawa T;Nosho K;Abril-Rodriguez G;Connolly C;Escuin-Ordinas H;Geybels MS;Grady WM;Hsu L;Hu-Lieskovan S;Huyghe JR;Kim YJ;Krystofinski P;Leiserson MDM;Montoya DJ;Nadel BB;Pellegrini M;Pritchard CC;Puig-Saus C;Quist EH;Raphael BJ;Salipante SJ;Shin DS;Shinbrot E;Shirts B;Shukla S;Stanford JL;Sun W;Tsoi J;Upfill-Brown A;Wheeler DA;Wu CJ;Yu M;Zaidi SH;Zaretsky JM;Gabriel SB;Lander ES;Garraway LA;Hudson TJ;Fuchs CS;Ribas A;Ogino S;Peters U
通讯作者：
Peters U
影响因子：
64.5
作者：
Chen B;Scurrah CR;McKinley ET;Simmons AJ;Ramirez-Solano MA;Zhu X;Markham NO;Heiser CN;Vega PN;Rolong A;Kim H;Sheng Q;Drewes JL;Zhou Y;Southard-Smith AN;Xu Y;Ro J;Jones AL;Revetta F;Berry LD;Niitsu H;Islam M;Pelka K;Hofree M;Chen JH;Sarkizova S;Ng K;Giannakis M;Boland GM;Aguirre AJ;Anderson AC;Rozenblatt-Rosen O;Regev A;Hacohen N;Kawasaki K;Sato T;Goettel JA;Grady WM;Zheng W;Washington MK;Cai Q;Sears CL;Goldenring JR;Franklin JL;Su T;Huh WJ;Vandekar S;Roland JT;Liu Q;Coffey RJ;Shrubsole MJ;Lau KS
通讯作者：
Lau KS
影响因子：
8.8
作者：
Bramsen, Jesper Bertram;Rasmussen, Mads Heilskov;Andersen, Claus Lindbjerg
通讯作者：
Andersen, Claus Lindbjerg
影响因子：
48
作者：
Browaeys, Robin;Saelens, Wouter;Saeys, Yvan
通讯作者：
Saeys, Yvan
影响因子：
16.6
作者：
Isella C;Brundu F;Bellomo SE;Galimi F;Zanella E;Porporato R;Petti C;Fiori A;Orzan F;Senetta R;Boccaccio C;Ficarra E;Marchionni L;Trusolino L;Medico E;Bertotti A
通讯作者：
Bertotti A