KL-6 is a potential diagnostic biomarker for pleural mesothelioma

Objectives Malignant pleural mesotheliomas (MPM) are associated with dismal outcome and the limited treatment options underscore the need for accurate and early diagnosis of MPM. The only currently approved circulating biomarker for MPM is the soluble mesothelin related protein (SMRP). The mucin MUC1, which forms mucous barriers and protects epithelial surfaces, has shown prognostic value as a biomarker in adenocarcinomas, prostate cancer and lung cancer. The present study investigates if KL-6 – a mucinous high-molecular weight glycoprotein – can serve as a diagnostic or prognostic marker of MPM.

Methods Using a chemiluminescent enzyme immunoassay to measure KL-6 and SMRP concentration, pleural effusion samples of 62 MPM patients and 25 patients with a benign pleural disorder were compared. Additionally, 50 and 20 corresponding serum samples were also analyzed.

Results Both peripheral blood and effusion based KL-6 concentrations were significantly higher in epithelioid mesothelioma (45 patients) when compared to patients with non-malignant pleural diseases (p<0.01 and p<0.001, respectively). Importantly, only 3 of 17 non-epithelioid effusion samples were out of the range of samples from patients with non-malignant pleural diseases. Furthermore, serum and pleural effusion KL-6 concentrations showed a highly significant correlation (p<0.001). Elevated effusion KL-6 concentration demonstrated no prognostic power in the epithelioid mesothelioma subcohort. Of note, pleural effusion derived KL-6 and SMRP demonstrated a highly significant correlation (p<0.0001).

Conclusion KL-6 is a potential liquid biopsy based biomarker and might be able to improve the diagnostic accuracy of current SMRP based test. Our findings warrant a prospective validation in order to determine the clinical feasibility of the proposed marker.

Publication History

Article published online:
09 March 2023