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Serum metabolome profiling in breast cancer risk assessment

SEMPRA Project

Polish-Norwegian joint research project funded in the frame of the Norwegian Financial Mechanism (Norway Grants) for years 2014-2021

Project realized in the frame of the GRIEG Program organized by the National Research Centre in co-operation with the Research Council of Norway.
Project number 2019/34/H/NZ7/00503.

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SEMPRA Project Description

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Breast cancer is among the most frequent types of cancer and the main causes of cancer-related deaths among women worldwide. Hence, it is one of the major health problems also in Poland and Norway. Prognosis of this malignancy, in addition to treatment efficacy, greatly depends on the stage of the disease at diagnosis. Therefore, many developed countries (including Poland and Norway) introduced mammography screening programs aimed at middle-aged women. However, due to several shortcomings of the current imaging techniques, supplementary molecular markers that could help early detection of breast cancer are warranted.

Although several risk factors of breast cancer are known, these are only associated with a fraction of the breast cancer cases. Blood metabolomics is a very powerful approach to reveal systemic conditions in the human body, particularly those related to disease development and progression. Therefore, blood metabolome is an emerging source of cancer biomarkers. However, little is known about metabolites that could be associated with cancer-promoting conditions and/or the existence of preclinical cancer, i.e. potential biomarkers feasible for breast cancer risk assessment and early detection.

The SEMPRA project concerns the possibility to estimate the risk of breast cancer based on a novel combination of molecular features with anthropometric and lifestyle-related features. We hypothesize that disease-related features of metabolism could be detected in serum, reflecting cancer-promoting conditions (e.g. chronic inflammation) and/or the existence of early “preclinical/symptomless” stages of the disease. We hypothesize that such features (metabolites) can be detected in the serum of individuals who were diagnosed with breast cancer a few years after blood sample collection, even though they were considered “healthy” at that time. Hence, the general hypothesis driving this project states that the combination of a serum metabolome profile and lifestyle-related risk factors will allow building a joint classification model for stratification of breast cancer risk in a healthy population.

Two complementary analytical metabolomics tools based on mass spectrometry and magnetic resonance spectroscopy will be used, which increases the possibility to detect and identify molecular components associated with breast cancer. Sample and data repository from a large population-based study performed in the Trøndelag region of Norway (HUNT2) will be involved, which provides a unique opportunity to work with a sufficiently large cohort of individuals where relevant medical, anthropometric and lifestyle data, as well as a long-term follow-up, are available. Furthermore, a reference group of women with actual (clinical) cancer (breast cancer and other solid cancers) will be recruited to the study.

Specific aims of the project include:

  • to identify serum metabolome signature that discriminates individuals who were diagnosed with breast cancer a few years after donating serum from women who remained free of breast cancer,
  • to compare the serum metabolome signature of a “high risk of breast cancer” with serum metabolome features of female patients with actual (clinical) breast cancer and other types of malignancies,
  • to build a classification model for the stratification of breast cancer risk in the population of healthy women, which will combine features of the serum metabolome and features associated with anthropometric and lifestyle-related risk factors.

The SEMPRA project provides a unique possibility to explore the underlying biological mechanisms in early breast cancer development, and possibly identify molecular targets to hinder cancer progression. The project could bring biomarker candidates to complement and enhance breast cancer screening programs helping to reduce “over-diagnosis” and subsequent “over-treatment” related to false-positive diagnoses. Hence, the project could contribute to pre-diagnostic management, early diagnosis, and successful treatment of breast cancer, which are issues with high health and socioeconomic impact in both participating countries.

SEMPRA Project Partners

Poland NIO logo

MSC-NRIO Gliwice is a medical research institute and one of the largest clinical institutions in Poland (the second largest comprehensive cancer center in Poland). There are about 1,700 employees, 500 hospital beds, and about 35,000 cancer patients treated annually. The scientific staff comprises about 200 researchers and clinicians, including 42 professors. Experimental research in the field of cancer biology has an over 70-year-long tradition (the research group has been involved in many aspects of basic research in oncology since 1948). In 2004 the Research Division was awarded the status of the “National Center of Excellence” by the Polish Ministry of Science. MSC-NRIO Gliwice has well-established scientific cooperation with many leading research and academic centers. Among others, it is a Sister Institution of M.D. Anderson Cancer Center. Currently, the Research Division is organized as the Center for Translational Research and Molecular Biology of Cancer. The research staff of the center consists of more than 50 investigators, including 12 professors and 35 post-doctoral researchers. Among the general goals of the center are novel methods of molecular diagnostics and experimental anticancer therapies.

Piotr Widłak

Prof. Piotr Widłak, Ph.D.
Laboratory of Clinical Proteomics
Center for Translational Research and Molecular Biology of Cancer

The Laboratory of Clinical Proteomics, headed by Prof. Piotr Widłak, has more than 10 years of experience in MS-based cancer proteomics and metabolomics. The group currently employs 6 researchers: 2 professors and 4 post-docs (with a background in molecular and medical biology, chemistry and bioinformatics) as well as 4 Ph.D. students and technician. The group has a strong multidisciplinary research co-operation, which include clinicians from clinical units of MSC-NRIO and other medical centers (e.g., Gdańsk Medical University), computer scientist and mathematicians from Silesian University of Technology, as well as mass spectrometrists from other centers (e.g., Institute of Bioorganic Chemistry in Poznan).

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NTNU is Norway’s largest university with more than 38,000 students. NTNU awards more than 300 Ph.D. degrees yearly within the fields of technology, science, arts and humanities, social sciences, and medicine and is a major participant in European funded projects including FP7 and Horizon 2020. The Faculty of Medicine and Health Sciences (MH) was established 40 years ago and is a center for both outstanding research and education. It is responsible for one of the world’s largest health studies (HUNT) and is home to Nobel Prize-winning scientists May Britt and Edvard Moser. MH has 1,200 employees and consists of nine departments along with five specialist centers that were established through highly competitive national grants. Together with St. Olavs Hospital, MH is responsible for Trondheim University Hospital, and the largest medical school in Norway. This close collaboration also ensures strong ties between basic research and patient-related research. Medical technology is a prioritized research area at MH, which is reflected in the research infrastructure available in the Dept. of Circulation and Medical Imaging.

Tone F. Bathen

Prof. Tone F. Bathen, Ph.D.
MR Cancer Group
Department of Circulation and Medical Imaging

The MR Cancer Group, headed by Professor Tone F. Bathen, has more than 25 years of experience from clinical MRI and NMR based metabolomics studies in cancer. The group’s translational approach to cancer research benefits from the close integration between NTNU and St. Olav’s University Hospital. The group currently employs 14 research scientists and postdocs, 14 Ph.D. students, and two senior engineers. The group has built a strong multidisciplinary research network both nationally and internationally, allowing multilevel integration of biological data for improved understanding of the underlying biological processes. The group is internationally recognized for its large-scale MR metabolomics studies of cancer.

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