Evidence map›Paper›PMID 36563681›Full record

ArticleCancer cell2023

Histopathologic and proteogenomic heterogeneity reveals features of clear cell renal cell carcinoma aggressiveness.

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 Kołodziejczak and 59 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cancer cell, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 164 papers.

0numbers the graph read from it
0cells of the map it votes in
164citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

164 citing papers in PubMed.

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104 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

69 authors.

Yize LiDepartment 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.
Tung-Shing M LihDepartment of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21213, USA.
Saravana M DhanasekaranDepartment of Pathology, University of Michigan, Ann Arbor, MI 48109, USA; Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI 48109, USA. Electronic address: saravana@med.umich.edu.
Rahul MannanDepartment of Pathology, University of Michigan, Ann Arbor, MI 48109, USA; Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI 48109, USA.
Lijun ChenDepartment of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21213, USA.
Marcin CieslikDepartment of Pathology, University of Michigan, Ann Arbor, MI 48109, USA; Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI 48109, USA; Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI 48109, USA.
Yige WuDepartment 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.
Rita Jiu-Hsien LuDepartment 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.
David J ClarkDepartment of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21213, USA.
Iga KołodziejczakInternational Institute for Molecular Oncology, 60-203 Poznań, Poland; Postgraduate School of Molecular Medicine, Medical University of Warsaw, 02-091 Warsaw, Poland.
Runyu HongInstitute for Systems Genetics, NYU Grossman School of Medicine, New York, NY 10016, USA; Department of Biochemistry and Molecular Pharmacology, NYU Grossman School of Medicine, New York, NY 10016, USA.
Siqi ChenDepartment 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.
Yanyan ZhaoDepartment 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.
Seema ChughDepartment of Pathology, University of Michigan, Ann Arbor, MI 48109, USA; Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI 48109, USA.
Wagma CaravanDepartment 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.
Nataly Naser Al DeenDepartment 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.
Noshad HosseiniDepartment of Pathology, University of Michigan, Ann Arbor, MI 48109, USA; Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI 48109, USA; Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI 48109, USA.
Chelsea J NewtonVan Andel Research Institute, Grand Rapids, MI 49503, USA.
Karsten KrugBroad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA 02142, USA.
Yuanwei XuDepartment of Chemical and Biomolecular Engineering, Johns Hopkins University Whiting School of Engineering, Baltimore, MD 21218, USA.
Kyung-Cho ChoDepartment of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21213, USA.
Yingwei HuDepartment of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21213, USA.
Yuping ZhangDepartment of Pathology, University of Michigan, Ann Arbor, MI 48109, USA; Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI 48109, USA.
Chandan Kumar-SinhaDepartment of Pathology, University of Michigan, Ann Arbor, MI 48109, USA; Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI 48109, USA.
Weiping MaDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
Anna CalinawanDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
Matthew A WyczalkowskiDepartment 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.
Michael C WendlMcDonnell 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; Department of Mathematics, Washington University in St. Louis, St. Louis, MO 63130, USA.
Yuefan WangDepartment of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21213, USA.
Shenghao GuoDepartment of Biomedical Engineering, Johns Hopkins University Whiting School of Engineering, Baltimore, MD 21218, USA.
Cissy ZhangDepartment of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21213, USA.
Anne LeDepartment of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21213, 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.
Aniket DagarDepartment of Pathology, University of Michigan, Ann Arbor, MI 48109, USA; Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI 48109, USA.
Alex HopkinsDepartment of Pathology, University of Michigan, Ann Arbor, MI 48109, USA; Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI 48109, USA.
Hanbyul ChoDepartment of Pathology, University of Michigan, Ann Arbor, MI 48109, USA; Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI 48109, USA; Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI 48109, USA.
Felipe da Veiga LeprevostDepartment of Pathology, University of Michigan, Ann Arbor, MI 48109, USA.
Xiaojun JingDepartment of Pathology, University of Michigan, Ann Arbor, MI 48109, USA; Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI 48109, USA.
Guo Ci TeoDepartment of Pathology, University of Michigan, Ann Arbor, MI 48109, USA; Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI 48109, USA.
Wenke LiuInstitute for Systems Genetics, NYU Grossman School of Medicine, New York, NY 10016, USA; Department of Biochemistry and Molecular Pharmacology, NYU Grossman School of Medicine, New York, NY 10016, USA.
Melissa A ReimersSiteman Cancer Center, Washington University in St. Louis, St. Louis, MO 63130, USA; Division of Medical Oncology, Department of Medicine, Washington University School of Medicine, 660 S. Euclid Avenue, St. Louis, MO 63110, USA.
Russell PachynskiSiteman Cancer Center, Washington University in St. Louis, St. Louis, MO 63130, USA; Division of Medical Oncology, Department of Medicine, Washington University School of Medicine, 660 S. Euclid Avenue, St. Louis, MO 63110, USA.
Alexander J LazarDepartments of Pathology and Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Arul M ChinnaiyanDepartment of Pathology, University of Michigan, Ann Arbor, MI 48109, USA; Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI 48109, USA; Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI 48109, USA.
Brian A Van TineDepartment of Medicine, Washington University in St. Louis, St. Louis, MO 63110, USA; Siteman Cancer Center, Washington University in St. Louis, St. Louis, MO 63130, USA.
Bing ZhangLester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX 77030, USA.
Karin D RodlandBiological Sciences Division, Pacific Northwest National Laboratory, Richland, WA 99354, USA.
Gad GetzBroad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA 02142, USA.
D R ManiBroad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA 02142, USA.
Pei WangDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
Feng ChenDepartment of Medicine, Washington University in St. Louis, St. Louis, MO 63110, USA; Siteman Cancer Center, Washington University in St. Louis, St. Louis, MO 63130, USA; Department of Cell Biology and Physiology, Washington University in St. Louis, St. Louis, MO 63130, USA.
Galen HostetterVan Andel Research Institute, Grand Rapids, MI 49503, USA.
Mathangi ThiagarajanFrederick National Laboratory for Cancer Research, Frederick, MD 21702, USA.
W Marston LinehanUrologic Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
David FenyöInstitute for Systems Genetics, NYU Grossman School of Medicine, New York, NY 10016, USA; Department of Biochemistry and Molecular Pharmacology, NYU Grossman School of Medicine, New York, NY 10016, USA.
Scott D JewellVan Andel Research Institute, Grand Rapids, MI 49503, USA.
Gilbert S OmennMichigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI 48109, USA; Department of Computational Medicine and Bioinformatics, 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.
Rohit MehraDepartment of Pathology, University of Michigan, Ann Arbor, MI 48109, USA; Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI 48109, USA.
Maciej WiznerowiczInternational Institute for Molecular Oncology, 60-203 Poznań, Poland; Heliodor Swiecicki Clinical Hospital in Poznań, ul. Przybyszewskiego 49, 60-355 Poznań, Poland; Poznań University of Medical Sciences, 61-701 Poznań, Poland.
Ana I RoblesOffice of Cancer Clinical Proteomics Research, National Cancer Institute, Rockville, MD 20850, USA.
Mehdi MesriOffice of Cancer Clinical Proteomics Research, National Cancer Institute, Rockville, MD 20850, USA.
Tara HiltkeOffice of Cancer Clinical Proteomics Research, National Cancer Institute, Rockville, MD 20850, USA.
Eunkyung AnOffice of Cancer Clinical Proteomics Research, National Cancer Institute, Rockville, MD 20850, USA.
Henry RodriguezOffice of Cancer Clinical Proteomics Research, National Cancer Institute, Rockville, MD 20850, USA.
Daniel W ChanDepartment of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21213, 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, USA.
Christopher J RickettsUrologic Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: chris.ricketts@nih.gov.
Alexey I NesvizhskiiDepartment of Pathology, University of Michigan, Ann Arbor, MI 48109, USA; Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI 48109, USA; Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI 48109, USA.
Hui ZhangDepartment of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21213, 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, USA. Electronic address: huizhang@jhu.edu.
Li DingDepartment 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. Electronic address: lding@wustl.edu.
Clinical Proteomic Tumor Analysis Consortium

Funding

UNC-CH CENTER FOR ENVIRONMENTAL HEALTH &SUSCEPTIBILITYP30ES010126 · NIEHS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Hazel B Nichols · 2001 to 2026
$36.3M
Molecular Therapeutics of Kidney Cancer: VHL Gene and Fumarate Hydratase GeneZIABC011038 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI LINEHAN, WILLIAM MARSTON · 2009 to 2025
$29.8M
Strategic Vision & Impact on Environmental HealthP30ES017885 · NIEHS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Dana Dolinoy · 2011 to 2026
$21.3M
Clinical Studies of the Molecular Genetic Basis of Kidney CancerZIABC011028 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI LINEHAN, WILLIAM MARSTON · 2009 to 2025
$17.9M
Clinical Nursing and Data Management CoreZIDBC011089 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI LINEHAN, WILLIAM MARSTON · 2009 to 2025
$17.4M
Proteogenomic Studies aimed at understanding ovarian tumor responses to agents targeting the DNA damage response and translating this knowledge into clinical benefitU01CA214114 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI BIRRER, MICHAEL, PAULOVICH, AMANDA G · 2017 to 2021
$8.4M
MICROSCALED PROTEOGENOMICS FOR CANCER CLINICAL TRIALSU01CA214125 · NCI · BAYLOR COLLEGE OF MEDICINE · PI ANURAG, MEENAKSHI, CARR, STEVEN A · 2017 to 2021
$7.0M
Proteogenomic Translational Research Center for Clinical ProteomicU01CA214116 · NCI · BATTELLE PACIFIC NORTHWEST LABORATORIES · PI DRUKER, BRIAN J, RODLAND, KARIN D · 2017 to 2021
$6.8M
Center for Advanced Multi-Omic Characterization of CancerU24CA271012 · NCI · BATTELLE PACIFIC NORTHWEST LABORATORIES · PI Tao Liu · 2022 to 2026
$6.6M
Proteogenomic Characterization of Tumor Tissues and Preclinical Models with High PrecisionU24CA271079 · NCI · JOHNS HOPKINS UNIVERSITY · PI DANIEL Wanyui CHAN, Hui Zhang · 2022 to 2026
$6.6M
Center of Excellence for High Throughput Proteogenomic CharacterizationU24CA210986 · NCI · BROAD INSTITUTE, INC. · PI CARR, STEVEN A, GILLETTE, MICHAEL A · 2016 to 2020
$6.4M
Center of Excellence for High Throughput Proteogenomic CharacterizationU24CA270823 · NCI · BROAD INSTITUTE, INC. · PI STEVEN A CARR, MICHAEL A GILLETTE · 2022 to 2026
$5.3M
NCI NIH HHS U01 CA214114NCI NIH HHS U01 CA214116NCI NIH HHS U01 CA214125NCI NIH HHS U24 CA210954NCI NIH HHS U24 CA210955NCI NIH HHS U24 CA210967NCI NIH HHS U24 CA210972NCI NIH HHS U24 CA210979NCI NIH HHS U24 CA210985NCI NIH HHS U24 CA210986NCI NIH HHS U24 CA210993NCI NIH HHS U24 CA270823NCI NIH HHS U24 CA271012NCI NIH HHS U24 CA271037NCI NIH HHS U24 CA271079NCI NIH HHS U24 CA271114NIEHS NIH HHS P30 ES010126NIEHS NIH HHS P30 ES017885
6 · The paper itself

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.

Indexed as

Carcinoma, Renal CellKidney NeoplasmsProteogenomicsBiomarkers, TumorHumansPrognosisTreatment OutcomeBiomarkers, Tumorclear cell renal cell carcinomaCPTACglycoproteomicshistologymetabolomephosphoproteomicsproteogenomicssingle-nuclei RNA-seqtumor heterogeneityUCHL1

Identifiers

PMID36563681
PMCPMC9839644

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