A deeper evaluation of cytokeratin fragment 21-1 as a lung cancer tumor marker and comparison of different assays.
Abstract
Studies show CYFRA 21-1 fragments of cytokeratin 19 (CK19) to be promising biomarkers for non-small cell lung cancer (NSCLC). Although previous literature identifies specific CYFRA 21-1 antibody binding epitopes, the exact molecular weight of the CK19 fragment being detected by current assays is not well-documented. Serum samples from 58 patients (lung cancer (N = 36), control (N = 22)) were used to measure CYFRA 21-1 across four different quantification assays: enzyme-linked immunosorbent assay (ELISA), chemiluminescent assay (ChLIA), electrochemiluminescence immunoassay (ECLIA), and compensated interferometric reader (CIR). In the cancer group, correlation between ECLIA and ELISA was high (R<i>(Pearson)</i> = 0.948, r<i>(Spearman)</i> = 0.868) while correlation between ECLIA vs ChLIA and ECLIA vs CIR was low (R= 0.005, r = -0.0593), (R = 0.0275, r = 0.167), respectively. In the control group, correlation between ECLIA and ELISA was high (R = 0.861, r = 0.927) while correlation between ECLIA vs ChLIA and ECLIA vs CIR was low (R = 0.0079, r = -0.0593), (R = 0.0244, r = -0.102), respectively. Compared to ECLIA, concordance coefficients (<i>p</i> <sub><i>c</i></sub> ) were poor (<i>p</i> <sub><i>c</i></sub> < 0.90) across all assays except for cancers group in ELISA (<i>p</i> <sub><i>c</i></sub> = 0.913). ECLIA was the only assay to report control ranges above 1 ng/mL CYFRA 21-1 (ECLIA, 1.14-21.59 ng/mL; ELISA, 0.79-24.26 ng/mL; ChLIA, 0.062-0.691 ng/mL; 0.08-7.68 ng/mL). Differing sizes of the protein being measured by each assay may have a role in the discrepancies observed. Given the different CYFRA 21-1 concentration estimates among assays, further characterization of the fragment and its release during epithelial malignancies, such as NSCLC, is imperative to developing effective biomarker assays.
EDRN PI Authors
Medline Author List
- Deppen S
- Godfrey CM
- Grogan EL
- Kammer MN
- Khalil TA
- Rowe DJ
- Vnencak-Jones CL
- Xiao D
- Zou Y