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Molecular Diagnostics

Higher platelet counts correlate to tumour progression and can be induced by intratumoural stroma in non-metastatic breast carcinomas

British Journal of Cancer volume 126, pages 464–471 (2022)Cite this article

Subjects

Abstract

Background

Platelets support tumour progression. However, their prognostic significance and relation to circulating tumour cells (CTCs) in operable breast cancer (BrCa) are still scarcely known and, thus, merit further investigation.

Methods

Preoperative platelet counts (PCs) were compared with clinical data, CTCs, 65 serum cytokines and 770 immune-related transcripts obtained using the NanoString technology.

Results

High normal PC (hPC; defined by the 75th centile cut-off) correlated with an increased number of lymph node metastases and mesenchymal CTCs in the 70 operable BrCa patients. Patients with hPC and CTC presence revealed the shortest overall survival compared to those with no CTC/any PC or even CTC/normal PC. Adverse prognostic impact of hPC was observed only in the luminal subtype, when 247 BrCa patients were analysed. hPC correlated with high content of intratumoural stroma, specifically its phenotype related to CD8+ T and resting mast cells, and an increased concentration of cytokines related to platelet activation or even production in bone marrow (i.e. APRIL, ENA78/CXCL5, HGF, IL16, IL17a, MDC/CCL22, MCP3, MMP1 and SCF).

Conclusions

Preoperative platelets evaluated alone and in combination with CTCs have prognostic potential in non-metastatic BrCa and define patients at the highest risk of disease progression, putatively benefiting from anti-platelet therapy.

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Fig. 1: Relationship between platelets and clinical data in breast cancer.
Fig. 2: Relationship between platelets and molecular data in breast cancer patients.
Fig. 3: Putative model of tumour progression involving regulation of platelet level by intratumoural stroma-derived factors.

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Data availability

The data that support the findings of this work are available from the corresponding author upon request. Immune-related transcriptome data are available at NCBI GEO under accession number GSE180186.

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Acknowledgements

We thank all patients who agreed to donate blood for this research. We would like to acknowledge Peter Grešner for providing statistics consultation within the services of the Centre of Biostatistics and Bioinformatics Analysis located at the Medical University of Gdańsk, Poland, working as part of “Excellence Initiative — Research University” (grant no. MNiSW 07/IDUB/2019/94).

Funding

This research was funded by the National Science Centre, grant number 2016/22/E/NZ4/00664 and the National Centre for Research and Development, grant number WPC/33/HESCAP/2018.

Author information

Authors and Affiliations

  1. Laboratory of Translational Oncology, Institute of Medical Biotechnology and Experimental Oncology, Medical University of Gdańsk, Gdańsk, Poland

    Natalia Bednarz-Knoll, Marta Popęda, Aleksandra Markiewicz & Anna J. Żaczek

  2. Department of Development of Nursing and Social and Medical Sciences, Medical University of Warsaw, Warsaw, Poland

    Tomasz Kryczka

  3. Department of Experimental Pharmacology, Medical Research Centre of Polish Academy of Science, Warsaw, Poland

    Tomasz Kryczka & Damian Strzemecki

  4. Oncological Prevention Department, Medical University of Warsaw, Warsaw, Poland

    Barbara Kozakiewicz

  5. Radiotherapy Unit, Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland

    Barbara Kozakiewicz

  6. Department of Breast Cancer and Reconstructive Surgery, Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland

    Katarzyna Pogoda

  7. Department of Pathomorphology, Medical University of Gdańsk, Gdańsk, Poland

    Jolanta Szade

  8. Department of Immunology, Medical University of Warsaw, Warsaw, Poland

    Damian Strzemecki

  9. Department of Medical Laboratory Diagnostics – Fahrenheit Biobank BBMRI.pl, Medical University of Gdańsk, Gdańsk, Poland

    Leszek Kalinowski

  10. BioTechMed Centre, Department of Mechanics of Materials and Structures, University of Technology, Gdańsk, Poland

    Leszek Kalinowski

  11. Department of Surgical Oncology, Medical University of Gdańsk, Gdańsk, Poland

    Jarosław Skokowski

  12. Institute of Functional Nano and Soft Materials (FUNSOM), Soochow University, Suzhou, Jiangsu, China

    Jian Liu

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Contributions

Conceptualisation, NB-K and AJZ; methodology, NB-K, TK, JSz, DS and JL; formal analysis, NB-K and MP; investigation, NB-K, TK, JSz, MP, AM, DS and JL; resources, BK, KP, LK, JS and AJZ; data curation, NB-K and MP; writing — original draft preparation, NB-K and AJZ.; writing — review and editing, all authors; visualisation, NB-K and MP; supervision, NB-K and AJZ; project administration, AJZ; funding acquisition, AJZ.

Corresponding authors

Correspondence to Natalia Bednarz-Knoll or Anna J. Żaczek.

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The authors declare no competing interests.

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Primary tumour samples and blood samples were collected from the patients according to a standard protocol approved by the Medical University of Gdansk ethics committee and upon signing an informed consent. This study was performed in accordance with the tenets of the Declaration of Helsinki.

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Bednarz-Knoll, N., Popęda, M., Kryczka, T. et al. Higher platelet counts correlate to tumour progression and can be induced by intratumoural stroma in non-metastatic breast carcinomas. Br J Cancer 126, 464–471 (2022). https://doi.org/10.1038/s41416-021-01647-9

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  • DOI: https://doi.org/10.1038/s41416-021-01647-9

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