Local expression of complement factor I in breast cancer cells correlates with poor survival and recurrence.
Author
Summary, in English
Tumor cells often evade killing by the complement system by overexpressing membrane-bound complement inhibitors. However, production of soluble complement inhibitors in cells other than hepatocytes was rarely reported. We screened several breast cancer cell lines for expression of soluble complement inhibitor, complement factor I (FI). We also analyzed local production of FI in tissue microarrays with tumors from 130 breast cancer patients by in situ hybridization and immunohistochemistry. We found expression of FI in breast adenocarcinoma cell line MDA-MB-468 and confirmed its functional activity. Expression of FI at mRNA and protein levels was also confirmed in tumor cells and tumor stroma, both in fibroblasts and infiltrating immune cells. Multivariate Cox regression analyses revealed that high expression of FI protein in tumor cells was correlated with significantly shorter cancer-specific survival (HR 2.8; 95 % CI 1.0-7.5; p = 0.048) and recurrence-free survival (HR 3.4; 95 % CI 1.5-7.4; p = 0.002). High FI expression was positively correlated with tumor size (p < 0.001), and Nottingham histological grade (p = 0.015) and associated with estrogen and progesterone receptor status (p = 0.03 and p = 0.009, respectively). Our data show that FI is expressed in breast cancer and is associated with unfavorable clinical outcome.
Department/s
- Protein Chemistry, Malmö
- Pathology, Malmö
- Tumor microenvironment
- BioCARE: Biomarkers in Cancer Medicine improving Health Care, Education and Innovation
Publishing year
2015
Language
English
Pages
467-478
Publication/Series
Cancer Immunology and Immunotherapy
Volume
64
Issue
4
Full text
- Available as PDF - 17 MB
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Links
Document type
Journal article
Publisher
Springer
Topic
- Cancer and Oncology
Status
Published
Research group
- Protein Chemistry, Malmö
- Pathology, Malmö
ISBN/ISSN/Other
- ISSN: 1432-0851