ArticleClinical biochemistry2017
A quantitative immunoassay for lung cancer biomarker CIZ1b in patient plasma.
Article in Clinical biochemistry, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed.
- Exploratory study on application of MALDI‑TOF‑MS to detect serum and urine peptides related to small cell lung carcinoma.Molecular medicine reports · 2020Trial
- IsoProDB: an integrated map of human protein isoforms for accelerated research.Database : the journal of biological databases and curation · 2026Article
- Identification of fibrinogen as a plasma protein binding partner for lecanemab biosimilar IgG.Annals of clinical and translational neurology · 2024Article
- Protein isoform-centric therapeutics: expanding targets and increasing specificity.Nature reviews. Drug discovery · 2024Review
- Aptamer-modified magnetic SERS substrate for label-based determination of cardiac troponin I.Mikrochimica acta · 2021Article
- Changing the landscape of non-small cell lung cancer disparities.Journal of cancer biology · 2021Article
- CIZ1-F, an alternatively spliced variant of the DNA replication protein CIZ1 with distinct expression and localisation, is overrepresented in early stage common solid tumours.Cell cycle (Georgetown, Tex.) · 2018Article
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Authors and funding
9 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectivesNon-invasive tests for early detection of lung cancer are an important unmet clinical need. CIZ1b plasma biomarker can discriminate stage 1 lung cancer from within high-risk groups with clinically useful accuracy, with ROC AUCs in excess of 0.9 for two independent retrospective cohorts, and could therefore meet this need. Our aim was to characterise the native state of the biomarker and develop a quantitative immunoassay. DESIGN AND
methodsSelective denaturation, preparative electrophoresis and mass spectrometry of human plasma were used to characterise the biomarker and interaction partners. A sandwich ELISA was generated, and specificity for CIZ1b biomarker tested on lung cancer patient plasma.
resultsCIZ1b biomarker is a denaturation-resistant complex between a C-terminal fragment of CIZ1 bearing the CIZ1b epitope specified by alternative splicing of exon14, and fibrinogen alpha chain. Reconstitution of the biomarker epitope with purified fibrinogen and CIZ1b, but not CIZ1a (non-alternatively spliced exon 14) confirmed the specificity of the results. The endogenous complex is highly stable in lung cancer plasma and can be quantified by pairing of a CIZ1b exon-junction specific antibody with detection of fibrinogen. Application of this sandwich ELISA to a prospectively collected development set of plasmas reveals the same level of accuracy as the western blot used to validate the discriminatory capability of the biomarker.
conclusionsUnexpected and unusual molecular structure of CIZ1b in native plasma has complicated immunoassay design, and delayed translation of this promising biomarker. However, CIZ1b can now be measured using a high-throughput, hospital-friendly sandwich ELISA format, overcoming an important barrier to further clinical development and application of this blood test for early stage lung cancer.
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