Extracellular vesicles as a source for non-invasive biomarkers from human urine and serum for the early diagnosis of urological cancers
Islam, Khirul (2022-08-17)
Extracellular vesicles as a source for non-invasive biomarkers from human urine and serum for the early diagnosis of urological cancers
(17.08.2022)
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-fe2022093060647
https://urn.fi/URN:NBN:fi-fe2022093060647
Tiivistelmä
Introduction: Urological cancers-particularly cancer in prostate, bladder as well as renal organs- are one of the major causes of morbidity and mortality worldwide. Although treatment of urological cancers has expanded in the past decade, the diagnosis of such cancers remains inadequate because of the absence of specific or sensitive tests. Recently extracellular vesicles (EVs) and their surface tetraspanins such as CD9, or CD63, or CD81 have gained extreme interest as a new biomarker due to their role in cell-cell interaction. We hypothesized that detection of these tetraspanins associated EVs directly from urine and serum enable us to discover new biomarkers for urological cancers. Thus, we developed a highly sensitive immunoaffinity assay that can detect EVs directly from urine and serum without the necessity of isolation procedure.
Methods: The EVs were captured directly from urine and serum of prostate, bladder, and renal cancer patients using tetraspanin specific monoclonal antibodies (CD9, or CD63, or CD81) and detected by same monoclonal antibodies through nanoparticle-aided time-resolved fluorescence detection. Isolated EVs were characterized and visualized with tetraspanin biomarkers and transmission electron microscopy (TEM), respectively.
Results: Our nanoparticle-aided tetraspanin assay can detect isolated vesicles with high sensitivity. The tetraspanin based CD63-CD63 assay showed significant separation of urine of prostate cancer patients (p=0.02, 2-fold) and renal cell carcinoma (p=0.001, 5-fold) patients from benign controls, respectively. Biomarkers are enriched on EV-fraction.
Conclusion: The results suggested that the vesicles from urine and serum of urological cancer patients exhibit varying amounts of tetraspanins (CD9 or CD81 or CD63). Measuring these varying amounts of tetraspanins expressions using highly sensitive non-invasive tools may play a key role in the early detection of urological cancers. The result obtained from this study warrant validation with well-defined large cohort of clinical samples.
Methods: The EVs were captured directly from urine and serum of prostate, bladder, and renal cancer patients using tetraspanin specific monoclonal antibodies (CD9, or CD63, or CD81) and detected by same monoclonal antibodies through nanoparticle-aided time-resolved fluorescence detection. Isolated EVs were characterized and visualized with tetraspanin biomarkers and transmission electron microscopy (TEM), respectively.
Results: Our nanoparticle-aided tetraspanin assay can detect isolated vesicles with high sensitivity. The tetraspanin based CD63-CD63 assay showed significant separation of urine of prostate cancer patients (p=0.02, 2-fold) and renal cell carcinoma (p=0.001, 5-fold) patients from benign controls, respectively. Biomarkers are enriched on EV-fraction.
Conclusion: The results suggested that the vesicles from urine and serum of urological cancer patients exhibit varying amounts of tetraspanins (CD9 or CD81 or CD63). Measuring these varying amounts of tetraspanins expressions using highly sensitive non-invasive tools may play a key role in the early detection of urological cancers. The result obtained from this study warrant validation with well-defined large cohort of clinical samples.