美国约翰霍普金斯大学Hui Zhang、Daniel W. Chan、西奈山伊坎医学院Pei Wang、密歇根大学Alexey I. Nesvizhskii、Marcin Cieslik等研究人员合作绘制了透明细胞肾细胞癌的蛋白基因组学整合图谱。相关论文于2019年10月31日发表于国际学术期刊《细胞》。

为了阐明驱动透明细胞肾细胞癌（ccRCC）的功能模块失调，研究人员对未经处理的ccRCC和配对的正常邻近组织样本进行了全面的基因组、表观基因组、转录组学、蛋白质组学和磷酸化蛋白质组学表征。基因组分析确定了与基因组不稳定性相关的独特分子亚组。蛋白质基因组学检测的整合唯一地确定了受基因组改变影响的细胞机制的蛋白质失调，包括氧化磷酸化相关的代谢、蛋白质翻译过程和磷酸信号模块。为了评估单个肿瘤中的免疫浸润程度，研究人员鉴定了微环境细胞特征，该特征描绘了四种以独特细胞途径为特征的、基于免疫的ccRCC亚型。这项研究报告了ccRCC的大规模蛋白基因组学分析，从而能够识别基因组改变的功能影响，并为基于ccRCC病理生物学的合理治疗选择提供了证据。

附：英文原文

Title: Integrated Proteogenomic Characterization of Clear Cell Renal Cell Carcinoma

Author: David J. Clark, Saravana M. Dhanasekaran, Francesca Petralia, Jianbo Pan, Xiaoyu Song, Yingwei Hu, Felipe da Veiga Leprevost, Boris Reva, Tung-Shing M. Lih, Hui-Yin Chang, Weiping Ma, Chen Huang, Christopher J. Ricketts, Lijun Chen, Azra Krek, Yize Li, Dmitry Rykunov, Qing Kay Li, Lin S. Chen, Umut Ozbek, Suhas Vasaikar, Yige Wu, Seungyeul Yoo, Shrabanti Chowdhury, Matthew A. Wyczalkowski, Jiayi Ji, Michael Schnaubelt, Andy Kong, Sunantha Sethuraman, Dmitry M. Avtonomov, Minghui Ao, Antonio Colaprico, Song Cao, Kyung-Cho Cho, Selim Kalayci, Shiyong Ma, Wenke Liu, Kelly Ruggles, Anna Calinawan, Zeynep H. Gümü, Daniel Geizler, Emily Kawaler, Guo Ci Teo, Bo Wen, Yuping Zhang, Sarah Keegan, Kai Li, Feng Chen, Nathan Edwards, Phillip M. Pierorazio, Xi Steven Chen, Christian P. Pavlovich, A. Ari Hakimi, Gabriel Brominski, James J. Hsieh, Andrzej Antczak, Tatiana Omelchenko, Jan Lubinski, Maciej Wiznerowicz, W. Marston Linehan, Christopher R. Kinsinger, Mathangi Thiagarajan, Emily S. Boja, Mehdi Mesri, Tara Hiltke, Ana I. Robles, Henry Rodriguez, Jiang Qian, David Feny, Bing Zhang, Li Ding, Eric Schadt

Issue&Volume: 2019/10/31

Abstract: To elucidate the deregulated functional modules that drive clear cell renal cell carcinoma (ccRCC), we performed comprehensive genomic, epigenomic, transcriptomic, proteomic, and phosphoproteomic characterization of treatment-naive ccRCC and paired normal adjacent tissue samples. Genomic analyses identified a distinct molecular subgroup associated with genomic instability. Integration of proteogenomic measurements uniquely identified protein dysregulation of cellular mechanisms impacted by genomic alterations, including oxidative phosphorylation-related metabolism, protein translation processes, and phospho-signaling modules. To assess the degree of immune infiltration in individual tumors, we identified microenvironment cell signatures that delineated four immune-based ccRCC subtypes characterized by distinct cellular pathways. This study reports a large-scale proteogenomic analysis of ccRCC to discern the functional impact of genomic alterations and provides evidence for rational treatment selection stemming from ccRCC pathobiology.

DOI: 10.1016/j.cell.2019.10.007

Source: https://www.cell.com/cell/fulltext/S0092-8674(19)31123-7