Early diagnosis of breast cancer : detection of altered glycosylation in human haptoglobin
Botti, Orsola (2020-11-10)
Early diagnosis of breast cancer : detection of altered glycosylation in human haptoglobin
Botti, Orsola
(10.11.2020)
Julkaisu on tekijänoikeussäännösten alainen. Teosta voi lukea ja tulostaa henkilökohtaista käyttöä varten. Käyttö kaupallisiin tarkoituksiin on kielletty.
suljettu
Julkaisun pysyvä osoite on:
https://urn.fi/URN:NBN:fi-fe2020120198937
https://urn.fi/URN:NBN:fi-fe2020120198937
Tiivistelmä
Breast cancer (BrCa) is the most common cancer in women worldwide, with 2.1 million of new cases occurring yearly, and the fifth most common cause of death in women. The five-year survival rate for early diagnosed BrCa is 80-90%, while it drops to 24-22% for cancers diagnosed at an advanced stage. Cancer biomarkers are an important target in research to achieve early diagnosis and improve the quality of cancer treatment.
The target biomarker in this research is haptoglobin (HPT), a glycoprotein that has two subunits with four N-glycosylation sites which can form oligomers so that the final possible glycovariants are numerous. In the presence of cancer, it is known that alterations occur in the glycan structures, making glycovariants important potential biomarkers for the detection of cancer from bodily fluids, since current diagnostic methods do not achieve a good level of sensitvity in the detection of cancer and its stages of development.
Six relevant pools from a BrCa cohort of 152 samples (which included cancerous and benign samples) and eight healthy samples were analyzed using an immobilized anti-HPT antibody and Eu+3-doped fluorescent nanoparticles, coated with glycan-binding proteins, which detected the glycan structures of HPT. HPT was used as the target antigen for the optimization of the assay, to achieve the best possible analytical performance. Finally, the samples were individually tested to assess the clinical performance of the assay, in comparison with an assay performed with the established conventional BrCa biomarker CA15-3.
One out of four glycan-binding proteins that showed potential (RCA) was selected for evaluating the clinical performance of the assay. Statistical evaluation of the assay performance in individual samples screening exhibited an overall poor analytical sensitivity of the assay, and case samples had lower signals compared to the other samples’ groups. Further studies on the other glycan binders are needed to evaluate the potential of HPT glycovariants as possible BrCa biomarkers, in order to achieve a better assay resolution and, consequently, a better discrimination between the pools.
The target biomarker in this research is haptoglobin (HPT), a glycoprotein that has two subunits with four N-glycosylation sites which can form oligomers so that the final possible glycovariants are numerous. In the presence of cancer, it is known that alterations occur in the glycan structures, making glycovariants important potential biomarkers for the detection of cancer from bodily fluids, since current diagnostic methods do not achieve a good level of sensitvity in the detection of cancer and its stages of development.
Six relevant pools from a BrCa cohort of 152 samples (which included cancerous and benign samples) and eight healthy samples were analyzed using an immobilized anti-HPT antibody and Eu+3-doped fluorescent nanoparticles, coated with glycan-binding proteins, which detected the glycan structures of HPT. HPT was used as the target antigen for the optimization of the assay, to achieve the best possible analytical performance. Finally, the samples were individually tested to assess the clinical performance of the assay, in comparison with an assay performed with the established conventional BrCa biomarker CA15-3.
One out of four glycan-binding proteins that showed potential (RCA) was selected for evaluating the clinical performance of the assay. Statistical evaluation of the assay performance in individual samples screening exhibited an overall poor analytical sensitivity of the assay, and case samples had lower signals compared to the other samples’ groups. Further studies on the other glycan binders are needed to evaluate the potential of HPT glycovariants as possible BrCa biomarkers, in order to achieve a better assay resolution and, consequently, a better discrimination between the pools.