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Liquid biopsy and multiparametric analysis in management of liver malignancies: new concepts of the patient stratification and prognostic approach

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Abstract

Background

The annually recorded incidence of primary hepatic carcinomas has significantly increased over the past two decades accounting for over 800 thousand of annual deaths caused by hepatocellular carcinoma (HCC) alone globally. Further, secondary liver malignancies are much more widespread compared to primary hepatic carcinomas: almost all solid malignancies are able to metastasise into the liver. The primary tumours most frequently metastasising to the liver are breast followed by colorectal carcinomas. Given the increased incidence of both primary and metastatic liver cancers, a new, revised approach is needed to advance medical care based on predictive diagnostics, innovative screening programmes, targeted preventive measures, and patient stratification for treatment algorithms tailored to individualised patient profile.

Advantages of the approach taken

The current pilot study took advantage of systemic alterations characteristic for liver malignancies, utilising liquid biopsy (blood samples) and specific biomarker patterns detected. Key molecular pathways relevant for pathomechanisms of liver cancers have been considered opening a perspective for both—individualised diagnostics and targeted treatment. Systemic alterations have been analysed prior to the therapy application avoiding molecular biological effects potentially diminishing predictive power of the biomarker-panel proposed. Multi-omics at DNA and protein (both expression and activity) levels has been applied. An established biomarker panel is considered as a powerful tool for individualised patient profiling and improved multi-level diagnostics—both predictive and prognostic ones.

Results and conclusions

Biomarker panels have been created for the patient stratification, prediction of a more optimal therapy and prognosis of survival based on the individualised patient profiling. Although there are some limitations of the pilot study performed, the results are encouraging, as it may be possible, through further research along these lines, to find a clinically and cost-effective means of stratifying liver cancer patients for personalised care and therapy. The benefits to the patient and society of accurate treatment stratification cannot be overemphasised.

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Abbreviations

HCC:

hepatocellular carcinoma

SIRT:

selective internal radiation therapy

TACE:

transarterial chemoembolisation

OS:

overall survival

MMP:

metalloproteinase

SOD-2:

superoxide-dismutase 2

PPPM:

predictive preventive personalised medicine

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Acknowledgements

The authors thank the Department of Radiology, University of Bonn for professional and financial support of the project. The authors are greatly thank the study nurse Mrs. Olga Ramig (Department of Radiology, University of Bonn, Germany) for collecting the patient data and personal supervision of the patients over the entire time of the project.

Funding

The study funding has been performed by the Department of Radiology, University of Bonn, Germany. Kristina Yeghiazaryan has been awarded a research fellowship with the European Association for Predictive, Preventive and Personalised Medicine (EPMA, Brussels, Belgium).

Author information

Author notes

  1. Olga Golubnitschaja and Jiri Polivka Jr contributed equally to this work.

Authors and Affiliations

  1. Department of Radiology, Rheinische Friedrich-Wilhelms-Universität Bonn, Sigmund-Freud-Str 25, 53105, Bonn, Germany

    Olga Golubnitschaja & Kristina Yeghiazaryan

  2. Breast Cancer Research Centre, Rheinische Friedrich-Wilhelms-Universität Bonn, Bonn, Germany

    Olga Golubnitschaja & Kristina Yeghiazaryan

  3. Centre for Integrated Oncology, Cologne-Bonn, Rheinische Friedrich-Wilhelms-Universität Bonn, Bonn, Germany

    Olga Golubnitschaja & Kristina Yeghiazaryan

  4. Department of Histology and Embryology, Faculty of Medicine in Pilsen, Charles University, Prague, Czech Republic

    Jiri Polivka Jr

  5. Biomedical Centre, Faculty of Medicine in Pilsen, Charles University, Prague, Czech Republic

    Jiri Polivka Jr

  6. Department of Neurology, University Hospital Pilsen, Pilsen, Czech Republic

    Jiri Polivka Jr

  7. Interventional Radiology, Department of Radiology, New York-Presbyterian Brooklyn Methodist Hospital, Brooklyn, NY, USA

    Leonard Berliner

Authors
  1. Olga Golubnitschaja
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  2. Jiri Polivka Jr
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  3. Kristina Yeghiazaryan
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  4. Leonard Berliner
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Contributions

O. Golubnitschaja created the concept of the project, made the data interpretation and drafted the article. J. Polivka Jr. carried out the statistical evaluation and graphical presentation of the data collected contributing significantly to the final version of the article. K. Yeghiazaryan carried out the molecular biological investigations. L. Berliner contributed to the data interpretation. All authors have read and approved the final manuscript.

Corresponding author

Correspondence to Olga Golubnitschaja.

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Competing interests

The authors declare that they have no competing interests.

Ethical approval

All the patients were informed about the purposes of the study and consequently have signed their “consent of the patient”. All investigations conformed to the principles outlined in the Declaration of Helsinki and were performed with permission from the responsible Ethical Committee of the Medical Faculty, Rheinische Friedrich-Wilhelms-University of Bonn. Corresponding reference number is 283/10.

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Golubnitschaja, O., Polivka, J., Yeghiazaryan, K. et al. Liquid biopsy and multiparametric analysis in management of liver malignancies: new concepts of the patient stratification and prognostic approach. EPMA Journal 9, 271–285 (2018). https://doi.org/10.1007/s13167-018-0146-6

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  • DOI: https://doi.org/10.1007/s13167-018-0146-6

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