IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v15y2024i1d10.1038_s41467-024-45475-w.html
   My bibliography  Save this article

Prediction of plasma ctDNA fraction and prognostic implications of liquid biopsy in advanced prostate cancer

Author

Listed:
  • Nicolette M. Fonseca

    (University of British Columbia)

  • Corinne Maurice-Dror

    (BC Cancer)

  • Cameron Herberts

    (University of British Columbia)

  • Wilson Tu

    (University of British Columbia)

  • William Fan

    (BC Cancer)

  • Andrew J. Murtha

    (University of British Columbia)

  • Catarina Kollmannsberger

    (BC Cancer)

  • Edmond M. Kwan

    (University of British Columbia
    BC Cancer
    School of Clinical Sciences; Monash University)

  • Karan Parekh

    (University of British Columbia)

  • Elena Schönlau

    (University of British Columbia)

  • Cecily Q. Bernales

    (University of British Columbia)

  • Gráinne Donnellan

    (University of British Columbia)

  • Sarah W. S. Ng

    (University of British Columbia)

  • Takayuki Sumiyoshi

    (University of British Columbia
    Kyoto University)

  • Joanna Vergidis

    (BC Cancer)

  • Krista Noonan

    (BC Cancer)

  • Daygen L. Finch

    (BC Cancer)

  • Muhammad Zulfiqar

    (BC Cancer)

  • Stacy Miller

    (BC Cancer)

  • Sunil Parimi

    (BC Cancer)

  • Jean-Michel Lavoie

    (BC Cancer)

  • Edward Hardy

    (Tom McMurtry & Peter Baerg Cancer Centre, Vernon Jubilee Hospital)

  • Maryam Soleimani

    (BC Cancer)

  • Lucia Nappi

    (University of British Columbia
    BC Cancer)

  • Bernhard J. Eigl

    (BC Cancer)

  • Christian Kollmannsberger

    (BC Cancer)

  • Sinja Taavitsainen

    (Tampere University and Tays Cancer Center)

  • Matti Nykter

    (Tampere University and Tays Cancer Center)

  • Sofie H. Tolmeijer

    (University of British Columbia
    Radboud University)

  • Emmy Boerrigter

    (Radboud University)

  • Niven Mehra

    (Radboud University)

  • Nielka P. Erp

    (Radboud University)

  • Bram Laere

    (Ghent University
    Ghent University
    Karolinska Institute)

  • Johan Lindberg

    (Karolinska Institute)

  • Henrik Grönberg

    (Karolinska Institute)

  • Daniel J. Khalaf

    (BC Cancer)

  • Matti Annala

    (University of British Columbia
    Tampere University and Tays Cancer Center)

  • Kim N. Chi

    (University of British Columbia
    BC Cancer)

  • Alexander W. Wyatt

    (University of British Columbia
    Michael Smith Genome Sciences Centre, BC Cancer)

Abstract

No consensus strategies exist for prognosticating metastatic castration-resistant prostate cancer (mCRPC). Circulating tumor DNA fraction (ctDNA%) is increasingly reported by commercial and laboratory tests but its utility for risk stratification is unclear. Here, we intersect ctDNA%, treatment outcomes, and clinical characteristics across 738 plasma samples from 491 male mCRPC patients from two randomized multicentre phase II trials and a prospective province-wide blood biobanking program. ctDNA% correlates with serum and radiographic metrics of disease burden and is highest in patients with liver metastases. ctDNA% strongly predicts overall survival, progression-free survival, and treatment response independent of therapeutic context and outperformed established prognostic clinical factors. Recognizing that ctDNA-based biomarker genotyping is limited by low ctDNA% in some patients, we leverage the relationship between clinical prognostic factors and ctDNA% to develop a clinically-interpretable machine-learning tool that predicts whether a patient has sufficient ctDNA% for informative ctDNA genotyping (available online: https://www.ctDNA.org ). Our results affirm ctDNA% as an actionable tool for patient risk stratification and provide a practical framework for optimized biomarker testing.

Suggested Citation

  • Nicolette M. Fonseca & Corinne Maurice-Dror & Cameron Herberts & Wilson Tu & William Fan & Andrew J. Murtha & Catarina Kollmannsberger & Edmond M. Kwan & Karan Parekh & Elena Schönlau & Cecily Q. Bern, 2024. "Prediction of plasma ctDNA fraction and prognostic implications of liquid biopsy in advanced prostate cancer," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-45475-w
    DOI: 10.1038/s41467-024-45475-w
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-024-45475-w
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-024-45475-w?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. Jacob J. Chabon & Emily G. Hamilton & David M. Kurtz & Mohammad S. Esfahani & Everett J. Moding & Henning Stehr & Joseph Schroers-Martin & Barzin Y. Nabet & Binbin Chen & Aadel A. Chaudhuri & Chih Lon, 2020. "Integrating genomic features for non-invasive early lung cancer detection," Nature, Nature, vol. 580(7802), pages 245-251, April.
    2. Viktor A. Adalsteinsson & Gavin Ha & Samuel S. Freeman & Atish D. Choudhury & Daniel G. Stover & Heather A. Parsons & Gregory Gydush & Sarah C. Reed & Denisse Rotem & Justin Rhoades & Denis Loginov & , 2017. "Scalable whole-exome sequencing of cell-free DNA reveals high concordance with metastatic tumors," Nature Communications, Nature, vol. 8(1), pages 1-13, December.
    3. Cameron Herberts & Matti Annala & Joonatan Sipola & Sarah W. S. Ng & Xinyi E. Chen & Anssi Nurminen & Olga V. Korhonen & Aslı D. Munzur & Kevin Beja & Elena Schönlau & Cecily Q. Bernales & Elie Ritch , 2022. "Deep whole-genome ctDNA chronology of treatment-resistant prostate cancer," Nature, Nature, vol. 608(7921), pages 199-208, August.
    4. Gillian Vandekerkhove & Jean-Michel Lavoie & Matti Annala & Andrew J. Murtha & Nora Sundahl & Simon Walz & Takeshi Sano & Sinja Taavitsainen & Elie Ritch & Ladan Fazli & Antonio Hurtado-Coll & Gang Wa, 2021. "Plasma ctDNA is a tumor tissue surrogate and enables clinical-genomic stratification of metastatic bladder cancer," Nature Communications, Nature, vol. 12(1), pages 1-12, December.
    5. Christopher Abbosh & Nicolai J. Birkbak & Gareth A. Wilson & Mariam Jamal-Hanjani & Tudor Constantin & Raheleh Salari & John Le Quesne & David A. Moore & Selvaraju Veeriah & Rachel Rosenthal & Teresa , 2017. "Phylogenetic ctDNA analysis depicts early-stage lung cancer evolution," Nature, Nature, vol. 545(7655), pages 446-451, May.
    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. Mingyun Bae & Gyuhee Kim & Tae-Rim Lee & Jin Mo Ahn & Hyunwook Park & Sook Ryun Park & Ki Byung Song & Eunsung Jun & Dongryul Oh & Jeong-Won Lee & Young Sik Park & Ki-Won Song & Jeong-Sik Byeon & Bo H, 2023. "Integrative modeling of tumor genomes and epigenomes for enhanced cancer diagnosis by cell-free DNA," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    2. Jonathan C. M. Wan & Dennis Stephens & Lingqi Luo & James R. White & Caitlin M. Stewart & Benoît Rousseau & Dana W. Y. Tsui & Luis A. Diaz, 2022. "Genome-wide mutational signatures in low-coverage whole genome sequencing of cell-free DNA," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    3. Xiao Zhou & Zhen Cheng & Mingyu Dong & Qi Liu & Weiyang Yang & Min Liu & Junzhang Tian & Weibin Cheng, 2022. "Tumor fractions deciphered from circulating cell-free DNA methylation for cancer early diagnosis," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    4. Aleix Prat & Fara Brasó-Maristany & Olga Martínez-Sáez & Esther Sanfeliu & Youli Xia & Meritxell Bellet & Patricia Galván & Débora Martínez & Tomás Pascual & Mercedes Marín-Aguilera & Anna Rodríguez &, 2023. "Circulating tumor DNA reveals complex biological features with clinical relevance in metastatic breast cancer," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    5. 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.
    6. Kate E. Stanley & Tatjana Jatsenko & Stefania Tuveri & Dhanya Sudhakaran & Lore Lannoo & Kristel Calsteren & Marie Borre & Ilse Parijs & Leen Coillie & Kris Bogaert & Rodrigo Almeida Toledo & Liesbeth, 2024. "Cell type signatures in cell-free DNA fragmentation profiles reveal disease biology," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    7. Bin Qiu & Wei Guo & Fan Zhang & Fang Lv & Ying Ji & Yue Peng & Xiaoxi Chen & Hua Bao & Yang Xu & Yang Shao & Fengwei Tan & Qi Xue & Shugeng Gao & Jie He, 2021. "Dynamic recurrence risk and adjuvant chemotherapy benefit prediction by ctDNA in resected NSCLC," Nature Communications, Nature, vol. 12(1), pages 1-11, December.
    8. Yaping Liu & Sarah C. Reed & Christopher Lo & Atish D. Choudhury & Heather A. Parsons & Daniel G. Stover & Gavin Ha & Gregory Gydush & Justin Rhoades & Denisse Rotem & Samuel Freeman & David W. Katz &, 2024. "FinaleMe: Predicting DNA methylation by the fragmentation patterns of plasma cell-free DNA," Nature Communications, Nature, vol. 15(1), pages 1-9, December.
    9. Mireia Crispin-Ortuzar & Ramona Woitek & Marika A. V. Reinius & Elizabeth Moore & Lucian Beer & Vlad Bura & Leonardo Rundo & Cathal McCague & Stephan Ursprung & Lorena Escudero Sanchez & Paula Martin-, 2023. "Integrated radiogenomics models predict response to neoadjuvant chemotherapy in high grade serous ovarian cancer," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    10. Alicia-Marie Conway & Simon P. Pearce & Alexandra Clipson & Steven M. Hill & Francesca Chemi & Dan Slane-Tan & Saba Ferdous & A. S. Md Mukarram Hossain & Katarzyna Kamieniecka & Daniel J. White & Clai, 2024. "A cfDNA methylation-based tissue-of-origin classifier for cancers of unknown primary," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    11. Xian Sun & Dongshuo Yin & Fei Qin & Hongfeng Yu & Wanxuan Lu & Fanglong Yao & Qibin He & Xingliang Huang & Zhiyuan Yan & Peijin Wang & Chubo Deng & Nayu Liu & Yiran Yang & Wei Liang & Ruiping Wang & C, 2023. "Revealing influencing factors on global waste distribution via deep-learning based dumpsite detection from satellite imagery," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    12. Maud Rijnders & J. Alberto Nakauma-González & Debbie G. J. Robbrecht & Alberto Gil-Jimenez & Hayri E. Balcioglu & Astrid A. M. Oostvogels & Maureen J. B. Aarts & Joost L. Boormans & Paul Hamberg & Mic, 2024. "Gene-expression-based T-Cell-to-Stroma Enrichment (TSE) score predicts response to immune checkpoint inhibitors in urothelial cancer," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    13. Harshabad Singh & Kristen E. Lowder & Kevin Kapner & Ronan J. Kelly & Hui Zheng & Nadine Jackson McCleary & Thomas A. Abrams & Jennifer A. Chan & Eileen M. Regan & Samuel J. Klempner & Alison M. Hanni, 2024. "Clinical outcomes and ctDNA correlates for CAPOX BETR: a phase II trial of capecitabine, oxaliplatin, bevacizumab, trastuzumab in previously untreated advanced HER2+ gastroesophageal adenocarcinoma," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    14. David Hsiehchen & Leslie Bucheit & Dong Yang & Muhammad Shaalan Beg & Mir Lim & Sunyoung S. Lee & Pashtoon Murtaza Kasi & Ahmed O. Kaseb & Hao Zhu, 2022. "Genetic features and therapeutic relevance of emergent circulating tumor DNA alterations in refractory non-colorectal gastrointestinal cancers," Nature Communications, Nature, vol. 13(1), pages 1-10, December.
    15. Yunyun An & Xin Zhao & Ziteng Zhang & Zhaohua Xia & Mengqi Yang & Li Ma & Yu Zhao & Gang Xu & Shunda Du & Xiang’an Wu & Shuowen Zhang & Xin Hong & Xin Jin & Kun Sun, 2023. "DNA methylation analysis explores the molecular basis of plasma cell-free DNA fragmentation," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    16. Maksymilian Prondzynski & Paul Berkson & Michael A. Trembley & Yashasvi Tharani & Kevin Shani & Raul H. Bortolin & Mason E. Sweat & Joshua Mayourian & Dogacan Yucel & Albert M. Cordoves & Beatrice Gab, 2024. "Efficient and reproducible generation of human iPSC-derived cardiomyocytes and cardiac organoids in stirred suspension systems," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    17. Dan Daniel Erdmann-Pham & Sanjit Singh Batra & Timothy K. Turkalo & James Durbin & Marco Blanchette & Iwei Yeh & Hunter Shain & Boris C. Bastian & Yun S. Song & Daniel S. Rokhsar & Dirk Hockemeyer, 2023. "Tracing cancer evolution and heterogeneity using Hi-C," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    18. Mary L. Stackpole & Weihua Zeng & Shuo Li & Chun-Chi Liu & Yonggang Zhou & Shanshan He & Angela Yeh & Ziye Wang & Fengzhu Sun & Qingjiao Li & Zuyang Yuan & Asli Yildirim & Pin-Jung Chen & Paul Winogra, 2022. "Cost-effective methylome sequencing of cell-free DNA for accurately detecting and locating cancer," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    19. Udit Singhal & Srinivas Nallandhighal & Jeffrey J. Tosoian & Kevin Hu & Trinh M. Pham & Judith Stangl-Kremser & Chia-Jen Liu & Razeen Karim & Komal R. Plouffe & Todd M. Morgan & Marcin Cieslik & Rober, 2024. "Integrative multi-region molecular profiling of primary prostate cancer in men with synchronous lymph node metastasis," Nature Communications, Nature, vol. 15(1), pages 1-9, December.
    20. Naser Ansari-Pour & Yonglan Zheng & Toshio F. Yoshimatsu & Ayodele Sanni & Mustapha Ajani & Jean-Baptiste Reynier & Avraam Tapinos & Jason J. Pitt & Stefan Dentro & Anna Woodard & Padma Sheila Rajagop, 2021. "Whole-genome analysis of Nigerian patients with breast cancer reveals ethnic-driven somatic evolution and distinct genomic subtypes," Nature Communications, Nature, vol. 12(1), pages 1-15, 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:15:y:2024:i:1:d:10.1038_s41467-024-45475-w. 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.