Differential detection of cancer antigen-125 glycovariant for the diagnosis of epithelial ovarian cancer
Nadeem, Nimrah (2020-04-01)
Differential detection of cancer antigen-125 glycovariant for the diagnosis of epithelial ovarian cancer
(01.04.2020)
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-fe2020051435576
https://urn.fi/URN:NBN:fi-fe2020051435576
Tiivistelmä
Cancer antigen 125 (CA125) is the established serum biomarker for epithelial ovarian cancer (EOC) diagnostic, however, it is also elevated in benign conditions such as endometriosis. Altered glycosylation during cancer progression is a universal phenomenon and the Sialyl-Tn antigen is one of the EOC-associated carbohydrate antigens. Therefore, we here evaluated whether an anti-STn-mAb could provide improved discrimination between CA125 in blood samples from patients with benign and malignant conditions.
CA125 from the OVCAR3 cell line, ascitic fluid of liver cirrhosis (LC) patients and placental homogenate (Pla) was captured on anti-CA125 mAb immobilized on microtitration wells. Anti-STn 1242 mAb coated onto fluorescent europium-chelates-doped nanoparticles (Eu-NPs) was used to detect altered glycans of immobilized CA125. Serum samples from EOC (n=85) and endometriosis (n=41) patients with marginally elevated conventional CA125 levels (35-200 U/ml) and from healthy female controls (n=23) were analyzed.
The new CA125STn assay, exhibited no cross-reactivity with LC or Pla- derived CA125. A highly significant (p < 0.0001) discrimination was found in marginally elevated EOC and endometriosis serum samples. The median difference between EOC and endometriosis was 16-fold as compared to 1.3-fold in the conventional CA125IA. The overall analytical sensitivity of the assay was found to be 0.35 U/ml.
Our results suggest that the CA125STn assay could decisively help to reduce the false-positive rate of the conventional CA125IA. Therefore, we hypothesize that this novel assay can offer an alternative to the CA125 biomarker, with improved utility for early EOC detection in population screening programs.
CA125 from the OVCAR3 cell line, ascitic fluid of liver cirrhosis (LC) patients and placental homogenate (Pla) was captured on anti-CA125 mAb immobilized on microtitration wells. Anti-STn 1242 mAb coated onto fluorescent europium-chelates-doped nanoparticles (Eu-NPs) was used to detect altered glycans of immobilized CA125. Serum samples from EOC (n=85) and endometriosis (n=41) patients with marginally elevated conventional CA125 levels (35-200 U/ml) and from healthy female controls (n=23) were analyzed.
The new CA125STn assay, exhibited no cross-reactivity with LC or Pla- derived CA125. A highly significant (p < 0.0001) discrimination was found in marginally elevated EOC and endometriosis serum samples. The median difference between EOC and endometriosis was 16-fold as compared to 1.3-fold in the conventional CA125IA. The overall analytical sensitivity of the assay was found to be 0.35 U/ml.
Our results suggest that the CA125STn assay could decisively help to reduce the false-positive rate of the conventional CA125IA. Therefore, we hypothesize that this novel assay can offer an alternative to the CA125 biomarker, with improved utility for early EOC detection in population screening programs.