美国约翰霍普金斯大学Hui Zhang等研究人员合作揭示胰腺导管腺癌的蛋白质基因组学特征。2021年9月16日出版的《细胞》杂志发表了这项成果。
为了了解驱动胰腺导管腺癌（PDAC）肿瘤发生的潜在分子改变，研究人员对140个胰腺癌、67个正常邻近组织和9个正常胰腺导管组织进行了全面的蛋白质基因组分析。蛋白质组学、磷蛋白组学和糖蛋白组学分析被用来描述蛋白质及其修饰的特征。此外，全基因组测序、全外显子组测序、甲基化、RNA测序（RNA-seq）和小RNA测序（miRNA-seq）也在同一组织上进行，用于促进综合蛋白质基因组分析，并确定基因组改变对蛋白质表达、信号通路和翻译后修饰的影响。
为了确保强大的下游分析，研究人员通过使用分子特征的多种正交策略评估了肿瘤的细胞性，并通过基于组织学审查的肿瘤细胞性的病理学估计进行了验证。这种PDAC的综合蛋白质基因组学特征将作为学界的宝贵资源，为早期检测和确定新的治疗靶标铺平道路。
据介绍，PDAC是一种高度侵袭性癌症，患者生存率低。
附：英文原文
Title: Proteogenomic characterization of pancreatic ductal adenocarcinoma
Author: Liwei Cao, Chen Huang, Daniel Cui Zhou, Yingwei Hu, T. Mamie Lih, Sara R. Savage, Karsten Krug, David J. Clark, Michael Schnaubelt, Lijun Chen, Felipe da Veiga Leprevost, Rodrigo Vargas Eguez, Weiming Yang, Jianbo Pan, Bo Wen, Yongchao Dou, Wen Jiang, Yuxing Liao, Zhiao Shi, Nadezhda V. Terekhanova, Song Cao, Rita Jui-Hsien Lu, Yize Li, Ruiyang Liu, Houxiang Zhu, Peter Ronning, Yige Wu, Matthew A. Wyczalkowski, Hariharan Easwaran, Ludmila Danilova, Arvind Singh Mer, Seungyeul Yoo, Joshua M. Wang, Wenke Liu, Benjamin Haibe-Kains, Mathangi Thiagarajan, Scott D. Jewell, Galen Hostetter, Chelsea J. Newton, Qing Kay Li, Michael H. Roehrl, David Feny, Pei Wang, Alexey I. Nesvizhskii, D.R. Mani, Gilbert S. Omenn, Emily S. Boja, Mehdi Mesri, Ana I. Robles, Henry Rodriguez, Oliver F. Bathe, Daniel W. Chan, Ralph H. Hruban, Li Ding, Bing Zhang, Hui Zhang, Mitual Amin, Eunkyung An, Christina Ayad, Thomas Bauer, Chet Birger, Michael J. Birrer, Simina M. Boca
Issue&Volume: 2021/09/16
Abstract: 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.
DOI: 10.1016/j.cell.2021.08.023
Source: https://www.cell.com/cell/fulltext/S0092-8674(21)00997-1