IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v13y2022i1d10.1038_s41467-022-29960-8.html
   My bibliography  Save this article

Integrative proteogenomic characterization of hepatocellular carcinoma across etiologies and stages

Author

Listed:
  • Charlotte K. Y. Ng

    (University Hospital Basel, University of Basel
    University Hospital Basel, University of Basel
    University of Bern
    SIB Swiss Institute of Bioinformatics)

  • Eva Dazert

    (University of Basel)

  • Tuyana Boldanova

    (University Hospital Basel, University of Basel
    University Hospital Basel)

  • Mairene Coto-Llerena

    (University Hospital Basel, University of Basel
    University Hospital Basel, University of Basel)

  • Sandro Nuciforo

    (University Hospital Basel, University of Basel)

  • Caner Ercan

    (University Hospital Basel, University of Basel)

  • Aleksei Suslov

    (University Hospital Basel, University of Basel)

  • Marie-Anne Meier

    (University Hospital Basel, University of Basel)

  • Thomas Bock

    (University of Basel)

  • Alexander Schmidt

    (University of Basel)

  • Sylvia Ketterer

    (University Hospital Basel, University of Basel)

  • Xueya Wang

    (University Hospital Basel, University of Basel)

  • Stefan Wieland

    (University Hospital Basel, University of Basel)

  • Matthias S. Matter

    (University Hospital Basel, University of Basel)

  • Marco Colombi

    (University of Basel)

  • Salvatore Piscuoglio

    (University Hospital Basel, University of Basel
    University Hospital Basel, University of Basel)

  • Luigi M. Terracciano

    (University Hospital Basel, University of Basel
    Humanitas Clinical and Research Center, IRCCS
    Humanitas University)

  • Michael N. Hall

    (University of Basel)

  • Markus H. Heim

    (University Hospital Basel, University of Basel
    University Hospital Basel)

Abstract

Proteogenomic analyses of hepatocellular carcinomas (HCC) have focused on early-stage, HBV-associated HCCs. Here we present an integrated proteogenomic analysis of HCCs across clinical stages and etiologies. Pathways related to cell cycle, transcriptional and translational control, signaling transduction, and metabolism are dysregulated and differentially regulated on the genomic, transcriptomic, proteomic and phosphoproteomic levels. We describe candidate copy number-driven driver genes involved in epithelial-to-mesenchymal transition, the Wnt-β-catenin, AKT/mTOR and Notch pathways, cell cycle and DNA damage regulation. The targetable aurora kinase A and CDKs are upregulated. CTNNB1 and TP53 mutations are associated with altered protein phosphorylation related to actin filament organization and lipid metabolism, respectively. Integrative proteogenomic clusters show that HCC constitutes heterogeneous subgroups with distinct regulation of biological processes, metabolic reprogramming and kinase activation. Our study provides a comprehensive overview of the proteomic and phophoproteomic landscapes of HCCs, revealing the major pathways altered in the (phospho)proteome.

Suggested Citation

  • Charlotte K. Y. Ng & Eva Dazert & Tuyana Boldanova & Mairene Coto-Llerena & Sandro Nuciforo & Caner Ercan & Aleksei Suslov & Marie-Anne Meier & Thomas Bock & Alexander Schmidt & Sylvia Ketterer & Xuey, 2022. "Integrative proteogenomic characterization of hepatocellular carcinoma across etiologies and stages," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-29960-8
    DOI: 10.1038/s41467-022-29960-8
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-022-29960-8
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-022-29960-8?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Hiroshi Tanaka & Hirofumi Arakawa & Tatsuya Yamaguchi & Kenji Shiraishi & Seisuke Fukuda & Kuniko Matsui & Yoshiki Takei & Yusuke Nakamura, 2000. "A ribonucleotide reductase gene involved in a p53-dependent cell-cycle checkpoint for DNA damage," Nature, Nature, vol. 404(6773), pages 42-49, March.
    2. Michael S. Lawrence & Petar Stojanov & Paz Polak & Gregory V. Kryukov & Kristian Cibulskis & Andrey Sivachenko & Scott L. Carter & Chip Stewart & Craig H. Mermel & Steven A. Roberts & Adam Kiezun & Pe, 2013. "Mutational heterogeneity in cancer and the search for new cancer-associated genes," Nature, Nature, vol. 499(7457), pages 214-218, July.
    3. Ying Jiang & Aihua Sun & Yang Zhao & Wantao Ying & Huichuan Sun & Xinrong Yang & Baocai Xing & Wei Sun & Liangliang Ren & Bo Hu & Chaoying Li & Li Zhang & Guangrong Qin & Menghuan Zhang & Ning Chen & , 2019. "Proteomics identifies new therapeutic targets of early-stage hepatocellular carcinoma," Nature, Nature, vol. 567(7747), pages 257-261, March.
    4. Daniel S. Chen & Ira Mellman, 2017. "Elements of cancer immunity and the cancer–immune set point," Nature, Nature, vol. 541(7637), pages 321-330, January.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Yuanyuan Qu & Jinwen Feng & Xiaohui Wu & Lin Bai & Wenhao Xu & Lingli Zhu & Yang Liu & Fujiang Xu & Xuan Zhang & Guojian Yang & Jiacheng Lv & Xiuping Chen & Guo-Hai Shi & Hong-Kai Wang & Da-Long Cao &, 2022. "A proteogenomic analysis of clear cell renal cell carcinoma in a Chinese population," Nature Communications, Nature, vol. 13(1), pages 1-21, December.
    2. Maria Pouyiourou & Bianca N. Kraft & Timothy Wohlfromm & Michael Stahl & Boris Kubuschok & Harald Löffler & Ulrich T. Hacker & Gerdt Hübner & Lena Weiss & Michael Bitzer & Thomas Ernst & Philipp Schüt, 2023. "Nivolumab and ipilimumab in recurrent or refractory cancer of unknown primary: a phase II trial," Nature Communications, Nature, vol. 14(1), pages 1-21, December.
    3. Aditi Sahu & Kivanc Kose & Lukas Kraehenbuehl & Candice Byers & Aliya Holland & Teguru Tembo & Anthony Santella & Anabel Alfonso & Madison Li & Miguel Cordova & Melissa Gill & Christi Fox & Salvador G, 2022. "In vivo tumor immune microenvironment phenotypes correlate with inflammation and vasculature to predict immunotherapy response," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
    4. Shaoshuai Tang & Yunzhi Wang & Rongkui Luo & Rundong Fang & Yufeng Liu & Hang Xiang & Peng Ran & Yexin Tong & Mingjun Sun & Subei Tan & Wen Huang & Jie Huang & Jiacheng Lv & Ning Xu & Zhenmei Yao & Qi, 2024. "Proteomic characterization identifies clinically relevant subgroups of soft tissue sarcoma," Nature Communications, Nature, vol. 15(1), pages 1-24, December.
    5. Alexandra Gyurdieva & Stefan Zajic & Ya-Fang Chang & E. Andres Houseman & Shan Zhong & Jaegil Kim & Michael Nathenson & Thomas Faitg & Mary Woessner & David C. Turner & Aisha N. Hasan & John Glod & Ro, 2022. "Biomarker correlates with response to NY-ESO-1 TCR T cells in patients with synovial sarcoma," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    6. Ambrocio Sanchez & Pedro Ortega & Ramin Sakhtemani & Lavanya Manjunath & Sunwoo Oh & Elodie Bournique & Alexandrea Becker & Kyumin Kim & Cameron Durfee & Nuri Alpay Temiz & Xiaojiang S. Chen & Reuben , 2024. "Mesoscale DNA features impact APOBEC3A and APOBEC3B deaminase activity and shape tumor mutational landscapes," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    7. E. H. Puttock & E. J. Tyler & M. Manni & E. Maniati & C. Butterworth & M. Burger Ramos & E. Peerani & P. Hirani & V. Gauthier & Y. Liu & G. Maniscalco & V. Rajeeve & P. Cutillas & C. Trevisan & M. Poz, 2023. "Extracellular matrix educates an immunoregulatory tumor macrophage phenotype found in ovarian cancer metastasis," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    8. Heng-Jia Liu & Heng Du & Damir Khabibullin & Mahsa Zarei & Kevin Wei & Gordon J. Freeman & David J. Kwiatkowski & Elizabeth P. Henske, 2023. "mTORC1 upregulates B7-H3/CD276 to inhibit antitumor T cells and drive tumor immune evasion," Nature Communications, Nature, vol. 14(1), pages 1-22, December.
    9. Feng Xie & Xiaoxue Zhou & Peng Su & Heyu Li & Yifei Tu & Jinjin Du & Chen Pan & Xiang Wei & Min Zheng & Ke Jin & Liyan Miao & Chao Wang & Xuli Meng & Hans Dam & Peter Dijke & Long Zhang & Fangfang Zho, 2022. "Breast cancer cell-derived extracellular vesicles promote CD8+ T cell exhaustion via TGF-β type II receptor signaling," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    10. Anna Luiza Silva Almeida Vicente & Alexei Novoloaca & Vincent Cahais & Zainab Awada & Cyrille Cuenin & Natália Spitz & André Lopes Carvalho & Adriane Feijó Evangelista & Camila Souza Crovador & Rui Ma, 2022. "Cutaneous and acral melanoma cross-OMICs reveals prognostic cancer drivers associated with pathobiology and ultraviolet exposure," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    11. Yan Li & Chen Xu & Bing Wang & Fujiang Xu & Fahan Ma & Yuanyuan Qu & Dongxian Jiang & Kai Li & Jinwen Feng & Sha Tian & Xiaohui Wu & Yunzhi Wang & Yang Liu & Zhaoyu Qin & Yalan Liu & Jing Qin & Qi Son, 2022. "Proteomic characterization of gastric cancer response to chemotherapy and targeted therapy reveals potential therapeutic strategies," Nature Communications, Nature, vol. 13(1), pages 1-26, December.
    12. Rotem Katzir & Noam Rudberg & Keren Yizhak, 2022. "Estimating tumor mutational burden from RNA-sequencing without a matched-normal sample," Nature Communications, Nature, vol. 13(1), pages 1-10, December.
    13. Mengxue Zhou & Jiaxin Wang & Jiaxing Pan & Hui Wang & Lujia Huang & Bo Hou & Yi Lai & Fengyang Wang & Qingxiang Guan & Feng Wang & Zhiai Xu & Haijun Yu, 2023. "Nanovesicles loaded with a TGF-β receptor 1 inhibitor overcome immune resistance to potentiate cancer immunotherapy," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    14. Oriol Pich & Iker Reyes-Salazar & Abel Gonzalez-Perez & Nuria Lopez-Bigas, 2022. "Discovering the drivers of clonal hematopoiesis," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    15. Meriem Messaoudene & Stéphanie Ferreira & Nathalie Saint-Lu & Mayra Ponce & Caroline Truntzer & Romain Boidot & Clément Bescop & Thomas Loppinet & Tanguy Corbel & Céline Féger & Karine Bertrand & Arie, 2024. "The DAV132 colon-targeted adsorbent does not interfere with plasma concentrations of antibiotics but prevents antibiotic-related dysbiosis: a randomized phase I trial in healthy volunteers," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    16. Shuaifeng Li & Shixun Han & Qi Zhang & Yibing Zhu & Haitao Zhang & Junli Wang & Yang Zhao & Jianhui Zhao & Lin Su & Li Li & Dawang Zhou & Cunqi Ye & Xin-Hua Feng & Tingbo Liang & Bin Zhao, 2022. "FUNDC2 promotes liver tumorigenesis by inhibiting MFN1-mediated mitochondrial fusion," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    17. Farshad Farshidfar & Kahn Rhrissorrakrai & Chaya Levovitz & Cong Peng & James Knight & Antonella Bacchiocchi & Juan Su & Mingzhu Yin & Mario Sznol & Stephan Ariyan & James Clune & Kelly Olino & Laxmi , 2022. "Integrative molecular and clinical profiling of acral melanoma links focal amplification of 22q11.21 to metastasis," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    18. Martin Boström & Erik Larsson, 2022. "Somatic mutation distribution across tumour cohorts provides a signal for positive selection in cancer," Nature Communications, Nature, vol. 13(1), pages 1-9, December.
    19. Shunli Fu & Lili Chang & Shujun Liu & Tong Gao & Xiao Sang & Zipeng Zhang & Weiwei Mu & Xiaoqing Liu & Shuang Liang & Han Yang & Huizhen Yang & Qingping Ma & Yongjun Liu & Na Zhang, 2023. "Temperature sensitive liposome based cancer nanomedicine enables tumour lymph node immune microenvironment remodelling," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    20. Jennifer B. Shah & Dana Pueschl & Bradley Wubbenhorst & Mengyao Fan & John Pluta & Kurt D’Andrea & Anna P. Hubert & Jake S. Shilan & Wenting Zhou & Adam A. Kraya & Alba Llop Guevara & Catherine Ruan &, 2022. "Analysis of matched primary and recurrent BRCA1/2 mutation-associated tumors identifies recurrence-specific drivers," Nature Communications, Nature, vol. 13(1), pages 1-19, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-29960-8. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.