Complement components as diagnostic, prognostic, and predictive biomarkers in patients with metastatictumors
Medical Review (Med. pregled), 2025, 61(6), 19-26.
Ts. Borisov1, D. Ferdinandov1,2, L. Roumenina3,4 , D. Metodiev5,6,7
1 Department of Neurosurgery, Faculty of Medicine, Medical University – Sofia
2 Clinic of Neurosurgery, University Hospital “Sv. Ivan Rilski” – Sofia
3 Centre de Recherche des Cordeliers, Institut National de la Santé et de la Recherche Médicale, Sorbonne Université, Université de Paris Cité, Team Inflammation, Complement and cancer – Paris
4 University Hospital Federation (FHU) COMET – Paris
5 Neuropathological Laboratory, University Hospital “Sv. Ivan Rilski” – Sofia
6 Clinical Pathology Laboratory, MHAT “Nadezda” Women’s Health Hospital – Sofia
7 Department of General and Clinical Pathology, Faculty of Medicine, Medical University – Sofia
Abstract. Biomarkers are important not only for early diagnosis but also for determining prognosis and building therapeutic strategies in patients with oncological diseases. The complement system, traditionally considered part of innate immunity, is now also recognized as an important regulator in the process of tumor progression. There is accumulating evidence that certain complement activation fragments, such as C3a, C5a and their receptors, C4d and Bb, as well as the regulators CFH, CD55 and CD59, may serve as diagnostic, prognostic and predictive biomarkers in different tumors, including at the metastatic stage. Circulating fragments C4d and Bb are associated with unfavorable prognosis in renal carcinoma, and serum levels of C4d are a reliable indi- cator for lung cancer. In experimental models, blockade of C5aR1 reduces metastatic load in bone lesions. Osteolytic changes in metastases are related by anaphylatoxins, which regulate osteoclast activity and create a favorable niche for neoplastic cells. Activation of microglia through the C3a/C5a axis contributes to immune suppression and tumor growth in brain metastases.
Expression of regulators such as CD55, CD59 and CFH in metastases suggests mechanisms of resistance to complement-dependent cytotoxicity. These data have prognostic significance regarding the response to radio-, chemoand immunotherapy, but must also be interpreted only in correlation with the histogenesis of the tumors, as the histological subtype of the neoplastic process may be important. The integration of complement biomarkers into combined panels, together with already established indicators, provides an opportunity to improve personalized therapy and precise monitoring of patients in the metastatic stage.
Key words: complement, metastatic stage, prognosis, therapy
Address for correspondence: Assoc. prof. Dilyan Ferdinandov, e-mail: ferdinandov@gmail.com