Assessment of circulating biomarkers for detection of lung cancer in a high-risk cohort

Article type: Research Article

Authors: Borg, Morten^{a; b; c; *} | Nederby, Line^d | Wen, Sara Witting Christensen^{e; f} | Hansen, Torben Frøstrup^{e; f} | Jakobsen, Anders^{e; f} | Andersen, Rikke Fredslund^{d; f} | Weinreich, Ulla Møller^{a; b} | Hilberg, Ole^{c; f}

Affiliations: [a] Department of Respiratory Diseases, Aalborg University Hospital, Aalborg, Denmark | [b] Department of Clinical Medicine, Aalborg University, Aalborg, Denmark | [c] Department of Internal Medicine, Lillebaelt Hospital, Vejle, Denmark | [d] Department of Clinical Biochemistry, Lillebaelt Hospital, Vejle, Denmark | [e] Department of Oncology, Lillebaelt Hospital, Vejle, Denmark | [f] Institute of Regional Health Research, University of Southern Denmark, Odense, Denmark

Correspondence: [*] Corresponding author: Morten Borg, Department of Respiratory Diseases, Aalborg University Hospital, Mølleparkvej 4, 9000 Aalborg, Denmark. Tel.: +45 97664800; E-mail: moklb@rn.dk.

Abstract: BACKGROUND: There is an urgent need for early detection of lung cancer. Screening with low-dose computed tomography (LDCT) is now implemented in the US. Supplementary use of a lung cancer biomarker with high specificity is desirable. OBJECTIVE: To assess the diagnostic properties of a biomarker panel consisting of cytokeratin 19 fragment (CYFRA 21-1), carcinoembryonic antigen (CEA) and cancer antigen 125 (CA125). METHODS: A cohort of 250 high-risk patients was investigated on suspicion of lung cancer. Ahead of diagnostic work-up, blood samples taken. Cross-validated prediction models were computed to assess lung cancer detection properties. RESULTS: In total 32% (79/250) of patients were diagnosed with lung cancer. Area under the curve (AUC) for the three biomarkers was of 0.795, with sensitivity/specificity of 57%/93% and negative predictive value of 83%. When combining the biomarkers with US screening criteria, the AUC was 0.809, while applying only US screening criteria on the cohort, yielded an AUC of 0.62. The ability of the biomarkers to detect stage I-II lung cancer was substantially lower; AUC 0.54. CONCLUSIONS: In a high-risk cohort, the detection properties of the three biomarkers were acceptable compared to current LDCT screening criteria. However, the ability to detect early stage lung cancer was low.

Keywords: Lung cancer, screening, biomarkers, cytokeratin 19 fragment (CYFRA 21-1), carcinoembryonic antigen (CEA), cancer antigen 125 (CA125)

DOI: 10.3233/CBM-210543

Journal: Cancer Biomarkers, vol. 36, no. 1, pp. 63-69, 2023