Proteogenomic characterization of pancreatic ductal adenocarcinoma,Cell

当前位置： X-MOL 学术 › Cell › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Proteogenomic characterization of pancreatic ductal adenocarcinoma
Cell ( IF 45.5 ) Pub Date : 2021-09-16 , DOI: 10.1016/j.cell.2021.08.023
Liwei Cao ₁ , Chen Huang ₂ , Daniel Cui Zhou ₃ , Yingwei Hu ₁ , T Mamie Lih ₁ , Sara R Savage ₂ , Karsten Krug ₄ , David J Clark ₁ , Michael Schnaubelt ₁ , Lijun Chen ₁ , Felipe da Veiga Leprevost ₅ , Rodrigo Vargas Eguez ₁ , Weiming Yang ₁ , Jianbo Pan ₁ , Bo Wen ₂ , Yongchao Dou ₂ , Wen Jiang ₂ , Yuxing Liao ₂ , Zhiao Shi ₂ , Nadezhda V Terekhanova ₃ , Song Cao ₃ , Rita Jui-Hsien Lu ₃ , Yize Li ₃ , Ruiyang Liu ₃ , Houxiang Zhu ₃ , Peter Ronning ₃ , Yige Wu ₃ , Matthew A Wyczalkowski ₃ , Hariharan Easwaran ₆ , Ludmila Danilova ₇ , Arvind Singh Mer ₈ , Seungyeul Yoo ₉ , Joshua M Wang ₁₀ , Wenke Liu ₁₀ , Benjamin Haibe-Kains ₁₁ , Mathangi Thiagarajan ₁₂ , Scott D Jewell ₁₃ , Galen Hostetter ₁₃ , Chelsea J Newton ₁₃ , Qing Kay Li ₁ , Michael H Roehrl ₁₄ , David Fenyö ₁₀ , Pei Wang ₉ , Alexey I Nesvizhskii ₅ , D R Mani ₄ , Gilbert S Omenn ₁₅ , Emily S Boja ₁₆ , Mehdi Mesri ₁₆ , Ana I Robles ₁₆ , Henry Rodriguez ₁₆ , Oliver F Bathe ₁₇ , Daniel W Chan ₁₈ , Ralph H Hruban ₁₉ , Li Ding ₃ , Bing Zhang ₂ , Hui Zhang ₁₈ ,

Affiliation

Department of Pathology, Johns Hopkins University, Baltimore, MD 21231, USA.
Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX 77030, USA; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
Department of Medicine, Washington University in St. Louis, St. Louis, MO 631110, USA; McDonnell Genome Institute, Washington University in St. Louis, St. Louis, MO 63108, USA.
Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA 02142, USA.
Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA.
The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD 21287, USA.
Department of Oncology, Johns Hopkins University, Baltimore, MD 21205, USA.
Princess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 1L7, Canada.
Sema4, a Mount Sinai venture, Stamford, CT 06902, USA.
Institute for Systems Genetics, NYU Grossman School of Medicine, New York, NY 10016, USA; Department of Biochemistry and Molecular Pharmacology, NYU Grossman School of Medicine, New York, NY 10016, USA.
Princess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 1L7, Canada; Department of Medical Biophysics, University of Toronto, Toronto, ON M5G 1L7, Canada.
Leidos Biomedical Research Inc., Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA.
Van Andel Research Institute, Grand Rapids, MI 49503, USA.
Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI 48109, USA.
Office of Cancer Clinical Proteomics Research, National Cancer Institute, Bethesda, MD 20892, USA.
Departments of Surgery and Oncology, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.
Department of Pathology, Johns Hopkins University, Baltimore, MD 21231, USA; The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD 21287, USA.
Department of Pathology, Johns Hopkins University, Baltimore, MD 21231, USA; The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD 21287, USA; The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University, Baltimore, MD 21231, USA.

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive cancer with poor patient survival. Toward understanding the underlying molecular alterations that drive PDAC oncogenesis, we conducted comprehensive proteogenomic analysis of 140 pancreatic cancers, 67 normal adjacent tissues, and 9 normal pancreatic ductal tissues. Proteomic, phosphoproteomic, and glycoproteomic analyses were used to characterize proteins and their modifications. In addition, whole-genome sequencing, whole-exome sequencing, methylation, RNA sequencing (RNA-seq), and microRNA sequencing (miRNA-seq) were performed on the same tissues to facilitate an integrated proteogenomic analysis and determine the impact of genomic alterations on protein expression, signaling pathways, and post-translational modifications. To ensure robust downstream analyses, tumor neoplastic cellularity was assessed via multiple orthogonal strategies using molecular features and verified via pathological estimation of tumor cellularity based on histological review. This integrated proteogenomic characterization of PDAC will serve as a valuable resource for the community, paving the way for early detection and identification of novel therapeutic targets.

中文翻译：

胰腺导管腺癌的蛋白质组学特征

胰腺导管腺癌（PDAC）是一种高度侵袭性的癌症，患者生存率很低。为了了解驱动 PDAC 肿瘤发生的潜在分子改变，我们对 140 例胰腺癌、67 例正常邻近组织和 9 例正常胰腺导管组织进行了全面的蛋白质组学分析。蛋白质组、磷酸蛋白质组和糖蛋白质组分析用于表征蛋白质及其修饰。此外，对同一组织进行全基因组测序、全外显子组测序、甲基化、RNA 测序 (RNA-seq) 和 microRNA 测序 (miRNA-seq)，以促进综合蛋白质组分析并确定基因组改变的影响蛋白质表达、信号传导途径和翻译后修饰。为了确保稳健的下游分析，使用分子特征通过多种正交策略评估肿瘤肿瘤细胞构成，并通过基于组织学检查的肿瘤细胞构成的病理估计进行验证。 PDAC 的这种综合蛋白质组学表征将成为社区的宝贵资源，为早期检测和识别新型治疗靶点铺平道路。

更新日期：2021-09-17

点击分享查看原文

点击收藏

公开下载

阅读更多本刊最新论文本刊介绍/投稿指南11