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Complement factor H as a marker for detection of bladder cancer.
Zhu-Zhu Cheng1, Michael J Corey, Maria Pärepalo
1Department of Bacteriology and Immunology, Haartman Institute and HUSLAB, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland.
Clinical Chemistry
|March 19, 2005
Summary
Factor H (FH) is identified as the bladder cancer tumor marker detected by the BTA TRAK assay. Factor H-related protein 1 (FHR-1) can inhibit this detection, suggesting a novel diagnostic mechanism.
Area of Science:
- Biochemistry
- Immunology
- Oncology
Background:
- The BTA TRAK and BTA stat assays for bladder cancer utilize monoclonal antibodies (mAbs) X13.2 and X52.1 to detect factor H (FH)-related material in urine.
- The precise ligands recognized by these mAbs have remained unidentified.
Purpose of the Study:
- To identify the specific ligands for mAbs X13.2 and X52.1.
- To elucidate the role of these ligands in the BTA TRAK assay for bladder cancer detection.
Main Methods:
- Western blot analyses were performed on purified FH, recombinant factor H-related protein 1 (FHR-1), and biological samples (serum and urine).
- Recombinant FH constructs were used to map antibody binding sites.
- Surface plasmon resonance was employed to assess potential competition by natural FH ligands.
- Functional assays using purified proteins and FH-depleted samples evaluated the role of ligands in the BTA TRAK assay.
Main Results:
- mAb X13.2 binds to domain 3 of FH and FH-like protein 1.
- mAb X52.1 binds to domain 18 of FH and FHR-1.
- Factor H (FH) was confirmed as the primary ligand detected by the BTA TRAK assay in patient urine.
- Factor H-related protein 1 (FHR-1) was found to inhibit the FH-dependent signal in the assay.
Conclusions:
- Factor H (FH) serves as a tumor marker for bladder cancer.
- The BTA TRAK assay detects FH for bladder cancer diagnosis.
- FHR-1 can partially inhibit FH detection, indicating a complex diagnostic mechanism involving both positive and negative signals.