| Literature DB >> 31675502 |
David J Clark1, Saravana M Dhanasekaran2, Francesca Petralia3, Jianbo Pan1, Xiaoyu Song4, Yingwei Hu1, Felipe da Veiga Leprevost2, Boris Reva3, Tung-Shing M Lih1, Hui-Yin Chang2, Weiping Ma3, Chen Huang5, Christopher J Ricketts6, Lijun Chen1, Azra Krek3, Yize Li7, Dmitry Rykunov3, Qing Kay Li1, Lin S Chen8, Umut Ozbek4, Suhas Vasaikar9, Yige Wu7, Seungyeul Yoo3, Shrabanti Chowdhury3, Matthew A Wyczalkowski7, Jiayi Ji4, Michael Schnaubelt1, Andy Kong2, Sunantha Sethuraman7, Dmitry M Avtonomov2, Minghui Ao1, Antonio Colaprico10, Song Cao7, Kyung-Cho Cho1, Selim Kalayci3, Shiyong Ma1, Wenke Liu11, Kelly Ruggles12, Anna Calinawan3, Zeynep H Gümüş3, Daniel Geiszler13, Emily Kawaler11, Guo Ci Teo2, Bo Wen5, Yuping Zhang2, Sarah Keegan11, Kai Li5, Feng Chen14, Nathan Edwards15, Phillip M Pierorazio16, Xi Steven Chen17, Christian P Pavlovich16, A Ari Hakimi18, Gabriel Brominski19, James J Hsieh20, Andrzej Antczak19, Tatiana Omelchenko21, Jan Lubinski22, Maciej Wiznerowicz23, W Marston Linehan6, Christopher R Kinsinger24, Mathangi Thiagarajan25, Emily S Boja24, Mehdi Mesri24, Tara Hiltke24, Ana I Robles24, Henry Rodriguez24, Jiang Qian26, David Fenyö11, Bing Zhang27, Li Ding7, Eric Schadt28, Arul M Chinnaiyan2, Zhen Zhang1, Gilbert S Omenn29, Marcin Cieslik30, Daniel W Chan31, Alexey I Nesvizhskii32, Pei Wang33, Hui Zhang34.
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.Entities:
Keywords: CPTAC; ccRCC; chromosomal translocation; drug targets; immune infiltration; phosphoproteomics; proteogenomics; proteomics; renal carcinoma; tumor microenvironment
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Year: 2019 PMID： 31675502 PMCID： PMC7331093 DOI： 10.1016/j.cell.2019.10.007
Source DB: PubMed Journal: Cell ISSN： 0092-8674 Impact factor: 41.582