A new diagnostic assay, developed by MSc Md. Ferdhos Khan in his PhD study, will help to more accurately distinguish patients with prostate cancer from those with benign prostatic hyperplasia.
Prostate cancer is a major public health concern, being the second most common cancer in men worldwide. It is also the fifth leading cause of cancer-related death in men globally. In 2022, prostate cancer was the most diagnosed cancer in males in Finland, with over 5500 new cases.
Prostate-specific antigen (PSA) is a key marker for early prostate cancer detection. However, the lack of specificity is a major limitation of the PSA test. The PSA test is effective in detecting men with prostate cancer, but PSA is also often elevated in men with benign prostatic hyperplasia.
PSA-based prostate cancer screening reduces cancer mortality, however, overdiagnosis and overtreatment may have adverse effects. So, new biomarkers are needed to replace or combine with PSA to improve the current diagnostic methods for early prostate cancer detection.
New method improved accuracy of prostate cancer detection
Measurement of different forms of PSA have been shown to improve early detection of prostate cancer. The routine prostate cancer screening method is based on measurement of the ratio of free to total PSA. Intact PSA (iPSA) is a subform of free PSA that can add the accuracy of prostate cancer detection and has become an essential part of PSA testing. It is part of the multi-kallikrein immunoassay used in diagnosing aggressive prostate cancer.
“It is a commonly used method in research and also I used it in my thesis work”, says Khan.
Multikallikrein panel measures the three different PSA forms and an additional kallikrein marker from blood. When these measures are combined with other clinical information including age, digital rectal examination, and biopsy history in a proprietary algorithm, the percent risk for a high-grade prostate cancer on biopsy is provided.
The measurement of iPSA is based on an antibody, which was developed at the Department of Biotechnology, University of Turku.
"The iPSA assay uses a unique antibody 4D4, but the performance characteristics of this antibody are however less than ideal when considering the construction of a robust routine assay. In my research, I used methods to improve the properties of the antibody so that it binds PSA more tightly. This allows the iPSA assay to measure even lower levels of PSA. This significantly increases the assay sensitivity compared to the previous assay and provides more accurate results," says Khan.
In the study, Khan used phage display technology to improve the binding affinity of the 4D4 antibody and developed an assay format for the sensitive and robust detection of iPSA. The study identified different mutants of the antibody, the use of which improved the accuracy of the iPSA assay in the detection of prostate cancer. The improved assay was evaluated in two groups of patients and compared with the current assay.
“The new assay was able to more accurately distinguish prostate cancer patients from those with benign prostatic hyperplasia and also improved the ability to separate benign and low-grade cancers from clinically significant cancers, especially in patients with smaller prostate volume," said Khan.
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Md. Ferdhos Liton Khan improved the binding affinity of the antibody by phage display technology and developed an assay construct with improved assay characteristic. The clinical utility of this assay was evaluated in two different patient groups and compared to the currently used assay.
The new assay improves the ability to distinguish between prostate cancer patients and benign conditions.
MSc, Md. Ferdhos Liton Khan defends the dissertation in Molecular Biotechnology and Diagnostics titled “Phage Display Modified Antibody to Free PSA Subform for Improved Prostate Cancer Detection” at the University of Turku on 25 October 2024 at 12.00 (University of Turku, Medisiina D, Alhopuro auditorium, Kiinamyllynkatu 10, Turku).
Opponent: M.D. Tobias Nordström (Karolinska Institutet Stockholm, Sweden)
Custos: Professor Urpo Lamminmäki (University of Turku)
