Plasma protein changes reflect colorectal cancer development and associated inflammation

Víctor Urbiola-Salvador; Agnieszka Jabłońska; Dominika Miroszewska; Qianru Huang; Katarzyna Duzowska; Kinga Drężek-Chyła; Marek Zdrenka; Ewa Śrutek; Łukasz Szylberg; Michał Jankowski; Dariusz Bała; Wojciech Zegarski; Tomasz Nowikiewicz; Wojciech Makarewicz; Agnieszka Adamczyk; Aleksandra Ambicka; Marcin Przewoźnik; Agnieszka Harazin-Lechowicz; Janusz Ryś; Natalia Filipowicz; Arkadiusz Piotrowski; Jan P Dumanski; Bin Li; Zhi Chen

doi:10.3389/fonc.2023.1158261

Plasma protein changes reflect colorectal cancer development and associated inflammation

Front Oncol. 2023 May 9:13:1158261. doi: 10.3389/fonc.2023.1158261. eCollection 2023.

Authors

Víctor Urbiola-Salvador¹, Agnieszka Jabłońska¹, Dominika Miroszewska¹, Qianru Huang², Katarzyna Duzowska³, Kinga Drężek-Chyła³, Marek Zdrenka⁴, Ewa Śrutek⁴, Łukasz Szylberg^{4

5}, Michał Jankowski^{6

7}, Dariusz Bała^{6

7}, Wojciech Zegarski^{6

7}, Tomasz Nowikiewicz^{6

8}, Wojciech Makarewicz⁹, Agnieszka Adamczyk¹⁰, Aleksandra Ambicka¹⁰, Marcin Przewoźnik¹⁰, Agnieszka Harazin-Lechowicz¹⁰, Janusz Ryś¹⁰, Natalia Filipowicz³, Arkadiusz Piotrowski³, Jan P Dumanski^{3

11

12}, Bin Li², Zhi Chen^{1

13}

Affiliations

¹ Intercollegiate Faculty of Biotechnology of University of Gdańsk and Medical University of Gdańsk, University of Gdańsk, Gdańsk, Poland.
² Center for Immune-Related Diseases at Shanghai Institute of Immunology, Department of Respiratory and Critical Care Medicine of Ruijin Hospital, Department of Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
³ 3P-Medicine Laboratory, Medical University of Gdańsk, Gdańsk, Poland.
⁴ Department of Tumor Pathology and Pathomorphology, Oncology Center-Prof. Franciszek Łukaszczyk Memorial Hospital, Bydgoszcz, Poland.
⁵ Department of Obstetrics, Gynaecology and Oncology, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, Bydgoszcz, Poland.
⁶ Surgical Oncology, Ludwik Rydygier's Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in ToruńSurgical Oncology, Ludwik Rydygier's Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, Toruń, Poland.
⁷ Department of Surgical Oncology, Oncology Center-Prof. Franciszek Łukaszczyk Memorial Hospital, Bydgoszcz, Poland.
⁸ Department of Breast Cancer and Reconstructive Surgery, Oncology Center-Prof. Franciszek Łukaszczyk Memorial Hospital, Bydgoszcz, Poland.
⁹ Clinic of General and Oncological Surgery, Specialist Hospital of Kościerzyna, Kościerzyna, Poland.
¹⁰ Department of Tumor Pathology, Maria Skłodowska-Curie National Research Institute of Oncology, Kraków, Poland.
¹¹ Department of Immunology, Genetics and Pathology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
¹² Department of Biology and Pharmaceutical Botany, Medical University of Gdańsk, Gdańsk, Poland.
¹³ Faculty of Biochemistry and Molecular Medicine, University of Oulu, Oulu, Finland.

Abstract

Introduction: Colorectal cancer (CRC) is the third most common malignancy and the second leading cause of death worldwide. Efficient non-invasive blood-based biomarkers for CRC early detection and prognosis are urgently needed.

Methods: To identify novel potential plasma biomarkers, we applied a proximity extension assay (PEA), an antibody-based proteomics strategy to quantify the abundance of plasma proteins in CRC development and cancer-associated inflammation from few μL of plasma sample.

Results: Among the 690 quantified proteins, levels of 202 plasma proteins were significantly changed in CRC patients compared to age-and-sex-matched healthy subjects. We identified novel protein changes involved in Th17 activity, oncogenic pathways, and cancer-related inflammation with potential implications in the CRC diagnosis. Moreover, the interferon γ (IFNG), interleukin (IL) 32, and IL17C were identified as associated with the early stages of CRC, whereas lysophosphatidic acid phosphatase type 6 (ACP6), Fms-related tyrosine kinase 4 (FLT4), and MANSC domain-containing protein 1 (MANSC1) were correlated with the late-stages of CRC.

Discussion: Further study to characterize the newly identified plasma protein changes from larger cohorts will facilitate the identification of potential novel diagnostic, prognostic biomarkers for CRC.

Keywords: biomarker; colorectal cancer; cytokines; early detection; inflammation; plasma proteomics; prognosis; proximity extension assay.

Copyright © 2023 Urbiola-Salvador, Jabłońska, Miroszewska, Huang, Duzowska, Drężek-Chyła, Zdrenka, Śrutek, Szylberg, Jankowski, Bała, Zegarski, Nowikiewicz, Makarewicz, Adamczyk, Ambicka, Przewoźnik, Harazin-Lechowicz, Ryś, Filipowicz, Piotrowski, Dumanski, Li and Chen.

Grants and funding

This research was funded by the National Science Centre of Poland, grant number 2018/30/Q/NZ6/00769 (granted to ZC). The CRC sample collection from the Medical University of Gdansk was sponsored by the Foundation for Polish Science (FNP) under the International Research Agendas Program (granted to JPD and AP), co-financed by the European Union under the European Regional Development Fund and via the “Excellence Initiative - Research University” program from Medical University of Gdańsk and The Swedish Cancer Society (granted to JPD).