Lectin nanoparticle assays for detecting breast cancer-associated glycovariants of cancer antigen 15-3 (CA15-3) in human plasma
Joonas Terävä, Leena Tiainen, Urpo Lamminmäki, Pirkko-Liisa Kellokumpu-Lehtinen, Kim Pettersson, Kamlesh Gidwani
https://urn.fi/URN:NBN:fi-fe2021042820802
Tiivistelmä
Cancer antigen 15–3 (CA15-3) is widely utilized for monitoring
metastatic breast cancer (BC). However, its utility for early detection
of breast cancer is severely limited due to poor clinical sensitivity
and specificity. The glycosylation of CA15-3 is known to be affected by
BC, and therefore it might offer a way to construct CA15-3 glycovariant
assays with improved cancer specificity. To this end, we performed
lectin-based glycoprofiling of BC-associated CA15-3. CA15-3 expressed by
a BC cell line was immobilized on microtitration wells using an
anti-CA15-3 antibody. The glycosylation of the immobilized CA15-3 was
then detected by using lectins coated onto europium (III)-doped
nanoparticles (Eu+3-NPs) and measuring the time-resolved fluorescence of Eu. Out of multiple lectin-Eu+3-NP preparations, wheat germ agglutinin (WGA) and macrophage galactose-type lectin (MGL) -Eu3+-NPs bound to the BC cell line-dericed CA15-3 glycovariants (CA15-3Lectin).
To evaluate the clinical performance of these two lectin-based assays,
plasma samples from metastatic BC patients (n = 53) and healthy
age-matched women (n = 20).Plasma CA15-3Lectin measurements
better distinguished metastatic BC patients from healthy controls than
the conventional CA15-3 immunoassay. At 90% specificity, the clinical
sensitivity of the assays was 66.0, 67.9 and 81.1% for the conventional
CA15-3, CA15-3MGL and CA15-3WGA assays, respectively. Baseline CA15-3MGL and CA15-3WGA
were correlated to conventional baseline CA15-3 levels (r = 0.68,
p<0.001, r = 0.90, p>0.001, respectively). However, very low
baseline CA15-3MGL levels ≤ 5 U/mL were common in this metastatic breast cancer patient population.In conclusion, the new CA15-3Lectin
concept could considerably improve the clinical sensitivity of BC
detection compared to the conventional CA15-3 immunoassays and should be
validated further on a larger series of subjects with different cancer
subtypes and stages.
Kokoelmat
- Rinnakkaistallenteet [19207]