Dissertation defence (Molecular Biotechnology and Diagnostics): MSc, Md. Ferdhos Liton Khan
Time
25.10.2024 at 12.00 - 16.00
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)
Doctoral Dissertation at UTUPub: https://urn.fi/URN:ISBN:978-951-29-9874-6
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Summary of the Doctoral Dissertation:
The aim of MSc Md. Ferdhos Liton Khan PhD project was to use phage display technique to address limitations in measuring a subform of PSA to better distinguish prostate cancer from benign conditions. The improved method was evaluated in two patient groups and compared to the currently used assay.
Prostate cancer (PCa) 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 deaths in men globally. In 2022, prostate cancer was the most diagnosed cancer in males in Finland, with 5514 new cases and 920 deaths. Prostate-specific antigen (PSA) is a key marker for early PCa detection. However, the lack of specificity is a major limitation of the PSA test. The PSA test is effective in detecting men with PCa, but PSA is also often elevated in men with benign prostatic hyperplasia. PSA-based PCa screening reduces PCa 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 PCa detection.
The discovery of various molecular forms of PSA led to the development of advanced immunoassays that enhance the specificity of PSA test to detect PCa. Intact PSA (iPSA) is a subform of free PSA that has become an essential part of PSA testing. In so called four kallikrein concept iPSA is measured in blood together with three other kallikrein markers. In the commercial 4Kscore test, these measures are combined with clinical information, including age, digital rectal examination, and biopsy history in a proprietary algorithm to provide the percent risk for a high-grade PCa on biopsy.
The measurement of iPSA is based on an antibody, which was developed at the Department of Biotechnology, University of Turku. The performance characteristics of the antibody are however less than ideal when considering the construction of a robust routine assay. 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.
The results were published in the Journal of Immunological Methods and the Journal of Applied Laboratory Medicine.
Opponent: M.D. Tobias Nordström (Karolinska Institutet Stockholm, Sweden)
Custos: Professor Urpo Lamminmäki (University of Turku)
Doctoral Dissertation at UTUPub: https://urn.fi/URN:ISBN:978-951-29-9874-6
***
Summary of the Doctoral Dissertation:
The aim of MSc Md. Ferdhos Liton Khan PhD project was to use phage display technique to address limitations in measuring a subform of PSA to better distinguish prostate cancer from benign conditions. The improved method was evaluated in two patient groups and compared to the currently used assay.
Prostate cancer (PCa) 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 deaths in men globally. In 2022, prostate cancer was the most diagnosed cancer in males in Finland, with 5514 new cases and 920 deaths. Prostate-specific antigen (PSA) is a key marker for early PCa detection. However, the lack of specificity is a major limitation of the PSA test. The PSA test is effective in detecting men with PCa, but PSA is also often elevated in men with benign prostatic hyperplasia. PSA-based PCa screening reduces PCa 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 PCa detection.
The discovery of various molecular forms of PSA led to the development of advanced immunoassays that enhance the specificity of PSA test to detect PCa. Intact PSA (iPSA) is a subform of free PSA that has become an essential part of PSA testing. In so called four kallikrein concept iPSA is measured in blood together with three other kallikrein markers. In the commercial 4Kscore test, these measures are combined with clinical information, including age, digital rectal examination, and biopsy history in a proprietary algorithm to provide the percent risk for a high-grade PCa on biopsy.
The measurement of iPSA is based on an antibody, which was developed at the Department of Biotechnology, University of Turku. The performance characteristics of the antibody are however less than ideal when considering the construction of a robust routine assay. 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.
The results were published in the Journal of Immunological Methods and the Journal of Applied Laboratory Medicine.
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