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.