Clinical significance of soluble CD26 in malignant pleural mesothelioma.

Nobukazu Fujimoto,Chikao Morimoto,Takumi Kishimoto,Taketo Yamada,Osamu Hosono,Kei Ohnuma,Keisuke Aoe,Deborah A Altomare

doi:10.1371/journal.pone.0115647

Abstract

There is no established single diagnostic marker for malignant pleural mesothelioma (MPM). CD26 is a 110 kDa, multifunctional, membrane-bound glycoprotein that has dipeptidyl peptidase IV (DPPIV) enzyme activity. The aim of this study was to evaluate the clinical significance of soluble CD26 (sCD26) in patients with MPM. The study included 80 MPM patients, 79 subjects with past asbestos exposure (SPE), and 134 patients with other benign pleural diseases (OPD) that were included as a control group. sCD26 levels and DPPIV activity in serum and/or pleural fluid were determined using an ELISA kit. Serum sCD26 levels and DPPIV enzyme activity in patients with MPM were significantly decreased compared with those in the SPE group (P = 0.000). The level of serum sCD26 was significantly decreased in patients with advanced stages of MPM compared with those with earlier stages (P = 0.047). The median OS of patients with MPM who had higher DPPIV enzyme activity was significantly longer than that of those with lower DPPIV enzyme activity (P = 0.032). The sCD26 levels in the pleural fluid of MPM patients with an epithelioid subtype were significantly increased compared with the OPD cohort (P = 0.012). Moreover, DPPIV enzyme activity in the pleural fluid of patients with MPM with an epithelioid subtype were significantly increased compared with those in the OPD cohort (P = 0.009). Patients with MPM who had lower specific DPPIV activity, determined as DPPIV/sCD26, showed significantly prolonged survival compared with those with higher specific DPPIV activity (P = 0.028). Serum sCD26 and DPPIV enzyme activity appear to be useful biomarkers for differentiating patients with MPM from SPE. The sCD26 levels or DPPIV enzyme activity in pleural fluid appear to be biomarkers in patients with an epithelioid subtype of MPM. DPPIV activity in serum or pleural fluid appears to be predictive for the prognosis of patients with MPM.

Highlights

Malignant pleural mesothelioma (MPM) is an aggressive malignancy arising from the mesothelial cells lining the pleura [1]
We examined the usefulness of serum and pleural fluid soluble CD26 (sCD26) levels and dipeptidyl peptidase IV (DPPIV) enzyme activity as clinical biomarkers of MPM
Serum sCD26 level and DPPIV enzyme activity were significantly decreased in patients with MPM compared with the subjects with past asbestos exposure (SPE) group

Summary

Introduction

Malignant pleural mesothelioma (MPM) is an aggressive malignancy arising from the mesothelial cells lining the pleura [1]. It is generally associated with a history of asbestos exposure [2] and has a very poor prognosis [3]. The incidence of MPM has increased in industrialized nations including Japan and the United States as a result of past wide-spread exposure to asbestos [4]. The incidence of MPM is predicted to increase in the decades, especially in developing countries where asbestos has not yet been banned [1, 4, 5]. Novel strategies for early diagnosis and screening of people with past asbestos exposure who are at high risk are urgently needed to improve the outcome

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