Väitös (molekulaarinen bioteknologia ja diagnostiikka): MSc, Md. Ferdhos Liton Khan
Aika
25.10.2024 klo 12.00 - 16.00
MSc, Md. Ferdhos Liton Khan esittää väitöskirjansa ”Phage Display Modified Antibody to Free PSA Subform for Improved Prostate Cancer Detection” julkisesti tarkastettavaksi Turun yliopistossa perjantaina 25.10.2024 klo 12.00 (Turun yliopisto, Medisiina D, Alhopuro-auditorio, Kiinamyllynkatu 10, Turku).
Vastaväittäjänä toimii tohtori Tobias Nordström (Karoliininen instituutti, Tukholma, Ruotsi) ja kustoksena professori Urpo Lamminmäki (Turun yliopisto). Tilaisuus on englanninkielinen. Väitöksen alana on molekulaarinen bioteknologia ja diagnostiikka.
Väitöskirja yliopiston julkaisuarkistossa: https://urn.fi/URN:ISBN:978-951-29-9874-6 (kopioi linkki selaimeen).
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Tiivistelmä väitöstutkimuksesta:
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.
Vastaväittäjänä toimii tohtori Tobias Nordström (Karoliininen instituutti, Tukholma, Ruotsi) ja kustoksena professori Urpo Lamminmäki (Turun yliopisto). Tilaisuus on englanninkielinen. Väitöksen alana on molekulaarinen bioteknologia ja diagnostiikka.
Väitöskirja yliopiston julkaisuarkistossa: https://urn.fi/URN:ISBN:978-951-29-9874-6 (kopioi linkki selaimeen).
***
Tiivistelmä väitöstutkimuksesta:
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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