Integrated Proteogenomic Characterization of Clear Cell Renal Cell Carcinoma
David Clark(Johns Hopkins University), Saravana M. Dhanasekaran(University of Michigan), Francesca Petralia(Icahn School of Medicine at Mount Sinai), Jianbo Pan(Johns Hopkins University), Xiaoyu Song(Icahn School of Medicine at Mount Sinai), Yingwei Hu(Johns Hopkins University), Felipe da Veiga Leprevost(University of Michigan), Boris Reva(Icahn School of Medicine at Mount Sinai), T. Mamie Lih(Johns Hopkins University), Hui-Yin Chang(University of Michigan), Weiping Ma(Icahn School of Medicine at Mount Sinai), Chen Huang(Baylor College of Medicine), Christopher J. Ricketts(National Institutes of Health), Lijun Chen(Johns Hopkins University), Azra Krek(Icahn School of Medicine at Mount Sinai), Yize Li(Washington University in St. Louis), Dmitry Rykunov(Icahn School of Medicine at Mount Sinai), Qing Kay Li(Johns Hopkins University), Lin S. Chen(Johns Hopkins University), Umut Özbek(Icahn School of Medicine at Mount Sinai), Suhas Vasaikar(The University of Texas MD Anderson Cancer Center), Yige Wu(Washington University in St. Louis), Seungyeul Yoo(Icahn School of Medicine at Mount Sinai), Shrabanti Chowdhury(Icahn School of Medicine at Mount Sinai), Matthew A. Wyczalkowski(Washington University in St. Louis), Jiayi Ji(Icahn School of Medicine at Mount Sinai), Michael Schnaubelt(Johns Hopkins University), Andy T. Kong(University of Michigan), Sunantha Sethuraman(Washington University in St. Louis), Dmitry M. Avtonomov(University of Michigan), Minghui Ao(Johns Hopkins University), Antonio Colaprico(University of Miami), Song Cao(Washington University in St. Louis), Kyung-Cho Cho(Johns Hopkins University), Selim Kalaycı(Icahn School of Medicine at Mount Sinai), Shiyong Ma(Johns Hopkins University), Wenke Liu(New York University), Kelly V. Ruggles(New York University), Anna Calinawan(Icahn School of Medicine at Mount Sinai), Zeynep H. Gümüş(Icahn School of Medicine at Mount Sinai), Daniel Geiszler(University of Michigan), Emily Kawaler(New York University), Guo Ci Teo(University of Michigan), Bo Wen(Baylor College of Medicine), Yuping Zhang(University of Michigan), Sarah Keegan(New York University), Kai Li(Baylor College of Medicine), Feng Chen(Washington University in St. Louis), Nathan Edwards(Georgetown University), Phillip M. Pierorazio(Johns Hopkins University), Xi Chen(University of Miami), Christian P. Pavlovich(Johns Hopkins University), A. Ari Hakimi(Memorial Sloan Kettering Cancer Center), Gabriel Bromiński(Poznan University of Medical Sciences), James J. Hsieh(Washington University in St. Louis), Andrzej Antczak(Poznan University of Medical Sciences), Tatiana Omelchenko(Memorial Sloan Kettering Cancer Center), Jan Lubiński(Pomeranian Medical University), Maciej Wiznerowicz(Poznan University of Medical Sciences), W. Marston Linehan(National Institutes of Health), Christopher R. Kinsinger(National Cancer Institute), Mathangi Thiagarajan(Frederick National Laboratory for Cancer Research), Emily S. Boja(National Cancer Institute), Mehdi Mesri(National Cancer Institute), Tara Hiltke(National Cancer Institute), Ana I. Robles(National Cancer Institute), Henry Rodriguez(National Cancer Institute), Jiang Qian(Johns Hopkins University), David Fenyö(New York University), Bing Zhang(Baylor College of Medicine), Li Ding(Washington University in St. Louis), Eric E. Schadt(Sema4 (United States)), Arul M. Chinnaiyan(University of Michigan), Zhen Zhang(Johns Hopkins University), Gilbert S. Omenn(University of Michigan), Marcin Cieślik(University of Michigan), Daniel W. Chan(Johns Hopkins University), Alexey I. Nesvizhskii(University of Michigan), Pei Wang(Icahn School of Medicine at Mount Sinai), Hui Zhang(Johns Hopkins University), A. Samad Hashimi, Alexander R. Pico, Alla Y. Karpova, Alyssa Charamut, Amanda G. Paulovich, Amy M. Perou, Anna Malovannaya(Icahn School of Medicine at Mount Sinai), Annette Marrero-Oliveras, Anupriya Agarwal, Barbara Hindenach, Barbara L. Pruetz, Beom‐Jun Kim(Memorial Sloan Kettering Cancer Center), Brian Druker, Chelsea J. Newton, Chet Birger, Corbin D. Jones, Cristina E. Tognon, D.R. Mani(National Cancer Institute), Dana R. Valley, Daniel C. Rohrer, Daniel Cui Zhou, Darlene Tansil, David Chesla(New York University), David I. Heiman(New York University), David A. Wheeler(New York University), Donghui Tan, Doug W. Chan(Johns Hopkins University), Emek Demir, Ewa P. Malc, Francesmary Modugno, Gaddy Getz, Galen Hostetter, George D. Wilson, Gerald W. Hart, Heng Zhu, Hongwei Liu(New York University), Houston Culpepper, Hua Sun(Washington University in St. Louis), Hua Zhou(Baylor College of Medicine), Jacob Day, James Suh(The University of Texas MD Anderson Cancer Center), Jasmine Huang(Baylor College of Medicine), Jason McDermott, Jeffrey R. Whiteaker, Jeffrey Tyner, Jennifer Eschbacher, Jin Chen(Memorial Sloan Kettering Cancer Center), John P. McGee, Jun Zhu(Johns Hopkins University), Karen A. Ketchum, Karin Rodland, Karl R. Clauser, Karna Robinson, Karsten Krug, Katherine A. Hoadley, Ki Sung Um, Kim Elburn(Memorial Sloan Kettering Cancer Center), Kimberly R. Holloway, Liang-Bo Wang(Icahn School of Medicine at Mount Sinai), Lili M. Blumenberg, Linda I. Hannick, Liqun Qi(Johns Hopkins University), Lori J. Sokoll, MacIntosh Cornwell, Marc Loriaux(University of Michigan), Marcin J. Domagalski, Marina A. Gritsenko, Matthew L. Anderson(Washington University in St. Louis), Matthew Monroe, Matthew J. Ellis, Maureen A. Dyer, Meenakshi Anurag, Meghan C. Burke, Melissa Borucki, Michael A. Gillette(Johns Hopkins University), Michael J. Birrer, Michael R. Lewis(Johns Hopkins University), Michael Ittmann, Michael J. Smith(Johns Hopkins University), Michael W. Vernon(Johns Hopkins University), Michelle Chaikin, Milan G. Chheda, Munziba Khan, Nancy Roche, Nathan Edwards(Georgetown University), Negin Vatanian, Nicole Tignor, Noam D. Beckmann, Pamela Grady, Patricia Castro, Paul Piehowski, Peter B. McGarvey, Piotr A. Mieczkowski, Pushpa Hariharan, Qingsong Gao, Rajiv Dhir, Ramani Kothadia, Ratna R. Thangudu, Rebecca Montgomery, Reyka G. Jayasinghe, Richard Smith, Robert A. Edwards(Georgetown University), Robert Zelt, Ross M. Bremner, Ruiyang Liu(New York University), Runyu Hong, Sailaja Mareedu, Samuel Payne, Sandra Cottingham, Sanford P. Markey, Scott D. Jewell, Shalin S. Patel, Shankha Satpathy, Shannon Richey, Sherri R. Davies, Shuang Cai, Simina M. Boca, Snehal Patil, Sohini Sengupta, Sonya Carter, Stacey Gabriel(Poznan University of Medical Sciences), Stefani N. Thomas, Stephanie Young, Stephen E. Stein, Steven A. Carr(University of Miami), Steven M. Foltz, S. G. Hilsenbeck, Tanya Krubit, Tao Liu(New York University), Tara Skelly(National Cancer Institute), Thomas F. Westbrook, Uma Borate, Uma Velvulou, Vladislav Petyuk, William Bocik, Xi Chen(University of Miami), Yan Shi(Johns Hopkins University), Yifat Geffen, Yihao Lu(Pomeranian Medical University), Ying Wang(Icahn School of Medicine at Mount Sinai), Yosef E. Maruvka, Zhi Li, Zhiao Shi(Johns Hopkins University), Zhidong Tu
Cited by 769Open Access
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.
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