Title: Histopathologic and proteogenomic heterogeneity reveals features of clear cell renal cell carcinoma aggressiveness
Author: Yize Li, Tung-Shing M. Lih, Saravana M. Dhanasekaran, Rahul Mannan, Lijun Chen, Marcin Cieslik, Yige Wu, Rita Jiu-Hsien Lu, David J. Clark, Iga Koodziejczak, Runyu Hong, Siqi Chen, Yanyan Zhao, Seema Chugh, Wagma Caravan, Nataly Naser Al Deen, Noshad Hosseini, Chelsea J. Newton, Karsten Krug, Yuanwei Xu, Kyung-Cho Cho, Yingwei Hu, Yuping Zhang, Chandan Kumar-Sinha, Weiping Ma, Anna Calinawan, Matthew A. Wyczalkowski, Michael C. Wendl, Yuefan Wang, Shenghao Guo, Cissy Zhang, Anne Le, Aniket Dagar, Alex Hopkins, Hanbyul Cho, Felipe da Veiga Leprevost, Xiaojun Jing, Guo Ci Teo, Wenke Liu, Melissa A. Reimers, Russell Pachynski, Alexander J. Lazar, Arul M. Chinnaiyan, Brian A. Van Tine, Bing Zhang, Karin D. Rodland, Gad Getz, D.R. Mani, Pei Wang, Feng Chen, Galen Hostetter, Mathangi Thiagarajan, W. Marston Linehan, David Feny, Scott D. Jewell, Gilbert S. Omenn
Issue&Volume: 2022-12-22
Abstract: Clear cell renal cell carcinomas (ccRCCs) represent ～75% of RCC cases and account for most RCC-associated deaths. Inter- and intratumoral heterogeneity (ITH) results in varying prognosis and treatment outcomes. To obtain the most comprehensive profile of ccRCC, we perform integrative histopathologic, proteogenomic, and metabolomic analyses on 305 ccRCC tumor segments and 166 paired adjacent normal tissues from 213 cases. Combining histologic and molecular profiles reveals ITH in 90% of ccRCCs, with 50% demonstrating immune signature heterogeneity. High tumor grade, along with BAP1 mutation, genome instability, increased hypermethylation, and a specific protein glycosylation signature define a high-risk disease subset, where UCHL1 expression displays prognostic value. Single-nuclei RNA sequencing of the adverse sarcomatoid and rhabdoid phenotypes uncover gene signatures and potential insights into tumor evolution. In vitro cell line studies confirm the potential of inhibiting identified phosphoproteome targets. This study molecularly stratifies aggressive histopathologic subtypes that may inform more effective treatment strategies.
DOI: 10.1016/j.ccell.2022.12.001
Source: https://www.cell.com/cancer-cell/fulltext/S1535-6108(22)00565-7
Cancer Cell：《癌细胞》，创刊于2002年。隶属于细胞出版社，最新IF：38.585
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本期文章：《癌细胞》：Online/在线发表
