Comprehensive proteogenomic characterization of rare kidney tumors
Ginny Xiaohe Li, Lijun Chen, Yi Hsiao, Rahul Mannan, Yuping Zhang, Jie Luo, Francesca Petralia, Hanbyul Cho, Noshad Hosseini, Felipe da Veiga Leprevost, Anna Calinawan, Yize Li, Shankara Anand, Aniket Dagar, Yifat Geffen, Chandan Kumar‐Sinha, Seema Chugh, Anne Le, Sean Ponce, Shenghao Guo, Cissy Zhang, Michael Schnaubelt, Nataly Naser Al Deen, Feng Chen, Wagma Caravan, Andrew Houston, Alex Hopkins, Chelsea J. Newton, Xiaoming Wang, Daniel A. Polasky, Sarah E. Haynes, Fengchao Yu, Xiaojun Jing, Siqi Chen, Ana I. Robles, Mehdi Mesri, Mathangi Thiagarajan, Eunkyung An, Gad Getz, W. Marston Linehan, Galen Hostetter, Scott D. Jewell, Daniel W. Chan, Pei Wang, Gilbert S. Omenn, Rohit Mehra, Christopher J. Ricketts, Li Ding, Arul M. Chinnaiyan, Marcin Cieślik, Saravana M. Dhanasekaran, Hui Zhang, Alexey I. Nesvizhskii, Alexander J. Lazar, Amanda G. Paulovich, Andrzej Antczak, Anthony R. Green, Avi Ma’ayan, Barb Pruetz, Bing Zhang, Boris Reva, Brian Druker, Charles A. Goldthwaite, Chet Birger, D.R. Mani, David Chesla, David Fenyö, Eric E. Schadt, George D. Wilson, Iga Kołodziejczak, Ivy John, Jason Hafron, Josh N. Vo, Kakhaber Zaalishvili, Karen A. Ketchum, Karin Rodland, Kristen Nyce, Maciej Wiznerowicz, Marcin J. Domagalski, Meenakshi Anurag, Melissa Borucki, Michael A. Gillette, Michael J. Birrer, Nathan Edwards, Negin Vatanian, Pamela VanderKolk, Peter B. McGarvey, Rajiv Dhir, Ratna R. Thangudu, Reese Crispen, Richard Smith, Samuel Payne, Sandra Cottingham, Shuang Cai, Steven A. Carr, Tao Liu, Toan Le, Weiping Ma, Xu Zhang, Lu Yin
Abstract
Non-clear cell renal cell carcinomas (non-ccRCCs) encompass diverse malignant and benign tumors. Refinement of differential diagnosis biomarkers, markers for early prognosis of aggressive disease, and therapeutic targets to complement immunotherapy are current clinical needs. Multi-omics analyses of 48 non-ccRCCs compared with 103 ccRCCs reveal proteogenomic, phosphorylation, glycosylation, and metabolic aberrations in RCC subtypes. RCCs with high genome instability display overexpression of IGF2BP3 and PYCR1. Integration of single-cell and bulk transcriptome data predicts diverse cell-of-origin and clarifies RCC subtype-specific proteogenomic signatures. Expression of biomarkers MAPRE3, ADGRF5, and GPNMB differentiates renal oncocytoma from chromophobe RCC, and PIGR and SOSTDC1 distinguish papillary RCC from MTSCC. This study expands our knowledge of proteogenomic signatures, biomarkers, and potential therapeutic targets in non-ccRCC.