A study to discover novel biomarker glycoforms of lung cancer
Jain, Shruti (2019-08-28)
A study to discover novel biomarker glycoforms of lung cancer
Jain, Shruti
(28.08.2019)
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-fe2019090627205
https://urn.fi/URN:NBN:fi-fe2019090627205
Tiivistelmä
Lung cancer (LuCa) is the second most common cancer among both women and men. Detection of LuCa is usually very late, at an advanced inoperable stage, for which the 5 year survival rate is only 4%. Early detection of lung cancer may result in better outcomes. Several serum biomarkers typically elevated in LuCa cases are glycoproteins which lack clinical specificity and sensitivity. It has been established that altered glycosylation is a universal phenomenon of cancer cells and the effects can be seen in glycoproteins secreted in circulation. Conventional double monoclonal immunoassays could not detect such changes as they are based on peptide epitope recognition. Our goal was to use glycan-binding proteins (lectins) to develop cancer-specific glycoforms of LuCa biomarkers and establish an assay with better clinical performance. The lectins generally have poor affinities towards its glycan epitope. Currently, we have the tool to improve its binding affinity through avidity effect by coating it on fluorescent europium-chelate doped 95 nm nanoparticles (Eu+3-NPs).
In this study five different glycoprotein biomarkers, cancer antigen 125 (CA125), cancer antigen 15-3 (CA 15-3), cancer antigen 19-9 (CA19-9), carcinoembryonic antigen (CEA), and human epididymis 4 (HE4), were used to create pools of plasma samples of LuCa patients and benign control for screening of lectin-NPs. These biomarkers were captured on microtiter wells using biomarker specific capture antibodies. A panel of lectins (n=55), each coated on Eu+3-NPs, were screened for detection of LuCa specific biomarkers. Screened lectins were then evaluated on individual plasma samples.
In pooled plasma samples, only CEA and CA125 showed discrimination between LuCa and benign control. In individual plasma samples, 5 lectin-nanoparticles (Dectin-1, NPA, MAA, SNA and Con A) could specifically bind to LuCa-CA125 and discriminate lung cancer from benign control. On testing a larger cohort of 110 individual plasma samples, NPA-NP showed more significant results compared to conventional CA125 immunoassay. With further testing and development, these lectin based assay could be used in specific and early lung cancer detection.
In this study five different glycoprotein biomarkers, cancer antigen 125 (CA125), cancer antigen 15-3 (CA 15-3), cancer antigen 19-9 (CA19-9), carcinoembryonic antigen (CEA), and human epididymis 4 (HE4), were used to create pools of plasma samples of LuCa patients and benign control for screening of lectin-NPs. These biomarkers were captured on microtiter wells using biomarker specific capture antibodies. A panel of lectins (n=55), each coated on Eu+3-NPs, were screened for detection of LuCa specific biomarkers. Screened lectins were then evaluated on individual plasma samples.
In pooled plasma samples, only CEA and CA125 showed discrimination between LuCa and benign control. In individual plasma samples, 5 lectin-nanoparticles (Dectin-1, NPA, MAA, SNA and Con A) could specifically bind to LuCa-CA125 and discriminate lung cancer from benign control. On testing a larger cohort of 110 individual plasma samples, NPA-NP showed more significant results compared to conventional CA125 immunoassay. With further testing and development, these lectin based assay could be used in specific and early lung cancer detection.