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 Haynes; Fengchao Yu; Xiaojun Jing; Siqi Chen; Ana I Robles; Mehdi Mesri; Mathangi Thiagarajan; Eunkyung An; Gad A 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 P Cieslik; Saravana M Dhanasekaran; Hui Zhang; Alexey I Nesvizhskii; Clinical Proteomic Tumor Analysis Consortium

doi:10.1016/j.xcrm.2024.101547

Comprehensive proteogenomic characterization of rare kidney tumors

Cell Rep Med. 2024 May 21;5(5):101547. doi: 10.1016/j.xcrm.2024.101547. Epub 2024 May 3.

Authors

Ginny Xiaohe Li¹, Lijun Chen², Yi Hsiao³, Rahul Mannan⁴, Yuping Zhang⁵, Jie Luo⁵, Francesca Petralia⁶, Hanbyul Cho⁷, Noshad Hosseini⁷, Felipe da Veiga Leprevost¹, Anna Calinawan⁶, Yize Li⁸, Shankara Anand⁹, Aniket Dagar⁵, Yifat Geffen¹⁰, Chandan Kumar-Sinha⁵, Seema Chugh⁵, Anne Le¹¹, Sean Ponce¹², Shenghao Guo¹³, Cissy Zhang², Michael Schnaubelt², Nataly Naser Al Deen⁸, Feng Chen¹⁴, Wagma Caravan⁸, Andrew Houston⁸, Alex Hopkins⁵, Chelsea J Newton¹⁵, Xiaoming Wang⁵, Daniel A Polasky¹, Sarah Haynes¹, Fengchao Yu¹, Xiaojun Jing⁵, Siqi Chen⁸, Ana I Robles¹⁶, Mehdi Mesri¹⁶, Mathangi Thiagarajan¹⁷, Eunkyung An¹⁶, Gad A Getz⁹, W Marston Linehan¹⁸, Galen Hostetter¹⁵, Scott D Jewell¹⁵, Daniel W Chan¹⁹, Pei Wang⁶, Gilbert S Omenn²⁰, Rohit Mehra⁵, Christopher J Ricketts¹⁸, Li Ding²¹, Arul M Chinnaiyan²², Marcin P Cieslik²³, Saravana M Dhanasekaran²⁴, Hui Zhang²⁵, Alexey I Nesvizhskii²⁶; Clinical Proteomic Tumor Analysis Consortium

Collaborators

Clinical Proteomic Tumor Analysis Consortium:
Alexander J Lazar, Amanda G Paulovich, Andrzej Antczak, Anthony Green, Avi Ma'ayan, Barb Pruetz, Bing Zhang, Boris Reva, Brian J Druker, Charles A Goldthwaite Jr, Chet Birger, D R Mani, David Chesla, David Fenyö, Eric E Schadt, George Wilson, Iga Kołodziejczak, Ivy John, Jason Hafron, Josh Vo, Kakhaber Zaalishvili, Karen A Ketchum, Karin D Rodland, Kristen Nyce, Maciej Wiznerowicz, Marcin J Domagalski, Meenakshi Anurag, Melissa Borucki, Michael A Gillette, Michael J Birrer, Nathan J Edwards, Negin Vatanian, Pamela VanderKolk, Peter B McGarvey, Rajiv Dhir, Ratna R Thangudu, Reese Crispen, Richard D Smith, Samuel H Payne, Sandra Cottingham, Shuang Cai, Steven A Carr, Tao Liu, Toan Le, Weiping Ma, Xu Zhang, Yin Lu, Yvonne Shutack, Zhen Zhang

Affiliations

¹ Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA.
² Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
³ Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI 48109, USA.
⁴ Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA; Michigan Center for Translational Pathology, Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA; Rogel Cancer Center, University of Michigan, Ann Arbor, MI 48109, USA.
⁵ Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA; Michigan Center for Translational Pathology, Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA.
⁶ Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
⁷ Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI 48109, USA; Michigan Center for Translational Pathology, Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA.
⁸ Department of Medicine, Washington University in St. Louis, St. Louis, MO 63110, USA; McDonnell Genome Institute, Washington University in St. Louis, St. Louis, MO 63108, USA.
⁹ Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA 02142, USA.
¹⁰ Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA 02142, USA; Cancer Center and Department of Pathology, Massachusetts General Hospital, Boston, MA 02115, USA.
¹¹ Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA; Department of Chemical and Biomolecular Engineering, Johns Hopkins University Whiting School of Engineering, Baltimore, MD 21218, USA; Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
¹² Department of Chemical and Biomolecular Engineering, Johns Hopkins University Whiting School of Engineering, Baltimore, MD 21218, USA.
¹³ Department of Biomedical Engineering, Johns Hopkins University Whiting School of Engineering, Baltimore, MD 21218, USA.
¹⁴ Department of Medicine, Washington University in St. Louis, St. Louis, MO 63110, USA.
¹⁵ Van Andel Research Institute, Grand Rapids, MI 49503, USA.
¹⁶ Office of Cancer Clinical Proteomics Research, National Cancer Institute, Rockville, MD 20850, USA.
¹⁷ Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA.
¹⁸ Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
¹⁹ Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA; Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA; Department of Urology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
²⁰ Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI 48109, USA; Michigan Center for Translational Pathology, Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA; Department of Internal Medicine, Human Genetics, and School of Public Health, University of Michigan, Ann Arbor, MI 48109, USA.
²¹ Department of Medicine, Washington University in St. Louis, St. Louis, MO 63110, USA; McDonnell Genome Institute, Washington University in St. Louis, St. Louis, MO 63108, USA; Department of Genetics, Washington University in St. Louis, St. Louis, MO 63130, USA; Siteman Cancer Center, Washington University in St. Louis, St. Louis, MO 63130, USA.
²² Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA; Michigan Center for Translational Pathology, Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA; Howard Hughes Medical Institute, University of Michigan, Ann Arbor, MI 48109, USA; Rogel Cancer Center, University of Michigan, Ann Arbor, MI 48109, USA; Department of Urology, University of Michigan, Ann Arbor, MI 48109, USA.
²³ Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA; Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI 48109, USA; Michigan Center for Translational Pathology, Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA.
²⁴ Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA; Michigan Center for Translational Pathology, Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA. Electronic address: saravana@umich.edu.
²⁵ Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA; Department of Chemical and Biomolecular Engineering, Johns Hopkins University Whiting School of Engineering, Baltimore, MD 21218, USA; Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA; Department of Urology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA. Electronic address: huizhang@jhu.edu.
²⁶ Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA; Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI 48109, USA; Michigan Center for Translational Pathology, Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA; Rogel Cancer Center, University of Michigan, Ann Arbor, MI 48109, USA. Electronic address: nesvi@med.umich.edu.

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.

Keywords: CPTAC; cell-of-origin; differential diagnosis biomarkers; glycoproteomics; metabolomics; non-clear cell renal cell carcinoma; phosphoproteomics; prognostic marker; proteogenomics; weighted genome instability index.

MeSH terms

Biomarkers, Tumor* / genetics
Biomarkers, Tumor* / metabolism
Carcinoma, Renal Cell* / genetics
Carcinoma, Renal Cell* / metabolism
Carcinoma, Renal Cell* / pathology
Female
Gene Expression Regulation, Neoplastic
Humans
Kidney Neoplasms* / genetics
Kidney Neoplasms* / metabolism
Kidney Neoplasms* / pathology
Male
Middle Aged
Proteogenomics* / methods
Transcriptome / genetics

Substances

Biomarkers, Tumor

Grants and funding

U24 CA271012/CA/NCI NIH HHS/United States