Evidence map›Paper›PMID 26757732›Full record

ArticleJournal of the National Cancer Institute2016

CAPG and GIPC1: Breast Cancer Biomarkers for Bone Metastasis Development and Treatment.

Jules A Westbrook, David A Cairns, Jianhe Peng, Valerie Speirs, Andrew M Hanby, Ingunn Holen, Steven L Wood, Penelope D Ottewell, Helen Marshall, Rosamonde E Banks and 3 more

Erratum issuedOpen access · bronzeAbstract readEditorial
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of the National Cancer Institute, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 51 papers.

0numbers the graph read from it
0cells of the map it votes in
51citing papers in PubMed
6.3field-weighted citation impact, top 2% of its field
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

51 citing papers in PubMed, 87 citations in OpenAlex.

  1. Trial
  2. Article
  3. Article
  4. Article
  5. FYB1-targeted modulation of CAPG promotes AML progression.Molecular and cellular biochemistry · 2025
    Article
  6. Article
  7. Review
  8. Article
  9. Organ-Specificity of Breast Cancer Metastasis.International journal of molecular sciences · 2023
    Review
  10. Article
  11. Article
  12. Kalkitoxin: A Potent Suppressor of Distant Breast Cancer Metastasis.International journal of molecular sciences · 2023
    Article
  13. Article
  14. Article
  15. Article
  16. Review
  17. Article
  18. Article
  19. Review
  20. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

13 authors at 3 institutions in 1 country.

Jules A WestbrookAffiliations of authors:Academic Unit of Clinical Oncology, University of Sheffield , Sheffield , UK (JAW*, IH, PDO, REC, JEB*); Cancer Research UK Leeds Centre (JAW, DAC, JP, SLW, REB, PJS, JEB), Clinical Trials Research Unit, Leeds Institute of Clinical Trials Research (DAC*, HM), and Clinical and Biomedical Proteomics Group (JAW, DAC, JP, SLW, REB, PJS, JEB) and Pathology and Tumor Biology (VS, AMH), Leeds Institute of Cancer and Pathology, University of Leeds , UK ; Department of Oncology and Metabolism, University of Sheffield, Sheffield , UK (SLW*).
David A CairnsAffiliations of authors:Academic Unit of Clinical Oncology, University of Sheffield , Sheffield , UK (JAW*, IH, PDO, REC, JEB*); Cancer Research UK Leeds Centre (JAW, DAC, JP, SLW, REB, PJS, JEB), Clinical Trials Research Unit, Leeds Institute of Clinical Trials Research (DAC*, HM), and Clinical and Biomedical Proteomics Group (JAW, DAC, JP, SLW, REB, PJS, JEB) and Pathology and Tumor Biology (VS, AMH), Leeds Institute of Cancer and Pathology, University of Leeds , UK ; Department of Oncology and Metabolism, University of Sheffield, Sheffield , UK (SLW*).
Jianhe PengAffiliations of authors:Academic Unit of Clinical Oncology, University of Sheffield , Sheffield , UK (JAW*, IH, PDO, REC, JEB*); Cancer Research UK Leeds Centre (JAW, DAC, JP, SLW, REB, PJS, JEB), Clinical Trials Research Unit, Leeds Institute of Clinical Trials Research (DAC*, HM), and Clinical and Biomedical Proteomics Group (JAW, DAC, JP, SLW, REB, PJS, JEB) and Pathology and Tumor Biology (VS, AMH), Leeds Institute of Cancer and Pathology, University of Leeds , UK ; Department of Oncology and Metabolism, University of Sheffield, Sheffield , UK (SLW*).
Valerie SpeirsAffiliations of authors:Academic Unit of Clinical Oncology, University of Sheffield , Sheffield , UK (JAW*, IH, PDO, REC, JEB*); Cancer Research UK Leeds Centre (JAW, DAC, JP, SLW, REB, PJS, JEB), Clinical Trials Research Unit, Leeds Institute of Clinical Trials Research (DAC*, HM), and Clinical and Biomedical Proteomics Group (JAW, DAC, JP, SLW, REB, PJS, JEB) and Pathology and Tumor Biology (VS, AMH), Leeds Institute of Cancer and Pathology, University of Leeds , UK ; Department of Oncology and Metabolism, University of Sheffield, Sheffield , UK (SLW*).
Andrew M HanbyAffiliations of authors:Academic Unit of Clinical Oncology, University of Sheffield , Sheffield , UK (JAW*, IH, PDO, REC, JEB*); Cancer Research UK Leeds Centre (JAW, DAC, JP, SLW, REB, PJS, JEB), Clinical Trials Research Unit, Leeds Institute of Clinical Trials Research (DAC*, HM), and Clinical and Biomedical Proteomics Group (JAW, DAC, JP, SLW, REB, PJS, JEB) and Pathology and Tumor Biology (VS, AMH), Leeds Institute of Cancer and Pathology, University of Leeds , UK ; Department of Oncology and Metabolism, University of Sheffield, Sheffield , UK (SLW*).
Ingunn HolenAffiliations of authors:Academic Unit of Clinical Oncology, University of Sheffield , Sheffield , UK (JAW*, IH, PDO, REC, JEB*); Cancer Research UK Leeds Centre (JAW, DAC, JP, SLW, REB, PJS, JEB), Clinical Trials Research Unit, Leeds Institute of Clinical Trials Research (DAC*, HM), and Clinical and Biomedical Proteomics Group (JAW, DAC, JP, SLW, REB, PJS, JEB) and Pathology and Tumor Biology (VS, AMH), Leeds Institute of Cancer and Pathology, University of Leeds , UK ; Department of Oncology and Metabolism, University of Sheffield, Sheffield , UK (SLW*).
Steven L WoodAffiliations of authors:Academic Unit of Clinical Oncology, University of Sheffield , Sheffield , UK (JAW*, IH, PDO, REC, JEB*); Cancer Research UK Leeds Centre (JAW, DAC, JP, SLW, REB, PJS, JEB), Clinical Trials Research Unit, Leeds Institute of Clinical Trials Research (DAC*, HM), and Clinical and Biomedical Proteomics Group (JAW, DAC, JP, SLW, REB, PJS, JEB) and Pathology and Tumor Biology (VS, AMH), Leeds Institute of Cancer and Pathology, University of Leeds , UK ; Department of Oncology and Metabolism, University of Sheffield, Sheffield , UK (SLW*).
Penelope D OttewellAffiliations of authors:Academic Unit of Clinical Oncology, University of Sheffield , Sheffield , UK (JAW*, IH, PDO, REC, JEB*); Cancer Research UK Leeds Centre (JAW, DAC, JP, SLW, REB, PJS, JEB), Clinical Trials Research Unit, Leeds Institute of Clinical Trials Research (DAC*, HM), and Clinical and Biomedical Proteomics Group (JAW, DAC, JP, SLW, REB, PJS, JEB) and Pathology and Tumor Biology (VS, AMH), Leeds Institute of Cancer and Pathology, University of Leeds , UK ; Department of Oncology and Metabolism, University of Sheffield, Sheffield , UK (SLW*).
Helen MarshallAffiliations of authors:Academic Unit of Clinical Oncology, University of Sheffield , Sheffield , UK (JAW*, IH, PDO, REC, JEB*); Cancer Research UK Leeds Centre (JAW, DAC, JP, SLW, REB, PJS, JEB), Clinical Trials Research Unit, Leeds Institute of Clinical Trials Research (DAC*, HM), and Clinical and Biomedical Proteomics Group (JAW, DAC, JP, SLW, REB, PJS, JEB) and Pathology and Tumor Biology (VS, AMH), Leeds Institute of Cancer and Pathology, University of Leeds , UK ; Department of Oncology and Metabolism, University of Sheffield, Sheffield , UK (SLW*).
Rosamonde E BanksAffiliations of authors:Academic Unit of Clinical Oncology, University of Sheffield , Sheffield , UK (JAW*, IH, PDO, REC, JEB*); Cancer Research UK Leeds Centre (JAW, DAC, JP, SLW, REB, PJS, JEB), Clinical Trials Research Unit, Leeds Institute of Clinical Trials Research (DAC*, HM), and Clinical and Biomedical Proteomics Group (JAW, DAC, JP, SLW, REB, PJS, JEB) and Pathology and Tumor Biology (VS, AMH), Leeds Institute of Cancer and Pathology, University of Leeds , UK ; Department of Oncology and Metabolism, University of Sheffield, Sheffield , UK (SLW*).
Peter J SelbyAffiliations of authors:Academic Unit of Clinical Oncology, University of Sheffield , Sheffield , UK (JAW*, IH, PDO, REC, JEB*); Cancer Research UK Leeds Centre (JAW, DAC, JP, SLW, REB, PJS, JEB), Clinical Trials Research Unit, Leeds Institute of Clinical Trials Research (DAC*, HM), and Clinical and Biomedical Proteomics Group (JAW, DAC, JP, SLW, REB, PJS, JEB) and Pathology and Tumor Biology (VS, AMH), Leeds Institute of Cancer and Pathology, University of Leeds , UK ; Department of Oncology and Metabolism, University of Sheffield, Sheffield , UK (SLW*).
Robert E ColemanAffiliations of authors:Academic Unit of Clinical Oncology, University of Sheffield , Sheffield , UK (JAW*, IH, PDO, REC, JEB*); Cancer Research UK Leeds Centre (JAW, DAC, JP, SLW, REB, PJS, JEB), Clinical Trials Research Unit, Leeds Institute of Clinical Trials Research (DAC*, HM), and Clinical and Biomedical Proteomics Group (JAW, DAC, JP, SLW, REB, PJS, JEB) and Pathology and Tumor Biology (VS, AMH), Leeds Institute of Cancer and Pathology, University of Leeds , UK ; Department of Oncology and Metabolism, University of Sheffield, Sheffield , UK (SLW*).
Janet E BrownAffiliations of authors:Academic Unit of Clinical Oncology, University of Sheffield , Sheffield , UK (JAW*, IH, PDO, REC, JEB*); Cancer Research UK Leeds Centre (JAW, DAC, JP, SLW, REB, PJS, JEB), Clinical Trials Research Unit, Leeds Institute of Clinical Trials Research (DAC*, HM), and Clinical and Biomedical Proteomics Group (JAW, DAC, JP, SLW, REB, PJS, JEB) and Pathology and Tumor Biology (VS, AMH), Leeds Institute of Cancer and Pathology, University of Leeds , UK ; Department of Oncology and Metabolism, University of Sheffield, Sheffield , UK (SLW*).
Cancer Research UK · GBUniversity of Leeds · GBUniversity of Sheffield · GB

Funding

Cancer Research UK 10048Cancer Research UK C18605/A 10048Department of Health RP-PG-0707-10101Medical Research Council G0802416
6 · The paper itself

Abstract

backgroundBone is the predominant site of metastasis from breast cancer, and recent trials have demonstrated that adjuvant bisphosphonate therapy can reduce bone metastasis development and improve survival. There is an unmet need for prognostic and predictive biomarkers so that therapy can be appropriately targeted.

methodsPotential biomarkers for bone metastasis were identified using proteomic comparison of bone-metastatic, lung-metastatic, and nonmetastatic variants of human breast cancer MDA-MB-231 cells. Clinical validation was performed using immunohistochemical staining of tumor tissue microarrays from patients in a large randomized trial of adjuvant zoledronic acid (zoledronate) (AZURE-ISRCTN79831382). We used Cox proportional hazards regression, the Kaplan-Meier estimate of the survival function, and the log-rank test to investigate associations between protein expression, clinical variables, and time to distant recurrence events. All statistical tests were two-sided.

resultsTwo novel biomarker candidates, macrophage-capping protein (CAPG) and PDZ domain-containing protein GIPC1 (GIPC1), were identified for clinical validation. Cox regression analysis of AZURE training and validation sets showed that control patients (no zoledronate) were more likely to develop first distant recurrence in bone (hazard ratio [HR] = 4.5, 95% confidence interval [CI] = 2.1 to 9.8, P < .001) and die (HR for overall survival = 1.8, 95% CI = 1.01 to 3.24, P = .045) if both proteins were highly expressed in the primary tumor. In patients with high expression of both proteins, zoledronate had a substantial effect, leading to 10-fold hazard ratio reduction (compared with control) for first distant recurrence in bone (P = .008).

conclusionsThe composite biomarker, CAPG and GIPC1 in primary breast tumors, predicted disease outcomes and benefit from zoledronate and may facilitate patient selection for adjuvant bisphosphonate treatment.

Indexed as

Adaptor Proteins, Signal TransducingBiomarkers, TumorBone Density Conservation AgentsBone NeoplasmsBreast NeoplasmsCell Line, TumorDiphosphonatesDisease ProgressionFemaleHumansImidazolesImmunohistochemistryKaplan-Meier EstimateLung NeoplasmsMicrofilament ProteinsMolecular Targeted TherapyAdaptor Proteins, Signal TransducingBiomarkers, TumorBone Density Conservation AgentsCAPG protein, humanDiphosphonatesGIPC1 protein, humanImidazolesMicrofilament ProteinsNuclear ProteinsZoledronic Acid

Identifiers

PMID26757732
PMCPMC4808632
OpenAlexW2262522273

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.