Clinical significance of soluble CD26 in malignant pleural mesothelioma

Our plain-English summary of Clinical significance of soluble CD26 in malignant pleural mesothelioma, by N. Fujimoto, K. Ohnuma, K. Aoe, et al (PloS One, 2014).

The study

• Authors: N. Fujimoto, K. Ohnuma, K. Aoe, O. Hosono, T. Yamada, T. Kishimoto, C. Morimoto
• Journal: PloS One
• Published: 2014;9(12):e115647
• Cited by: 9 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

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.

In plain English

This Japanese study measured the protein soluble CD26 (sCD26) and its enzyme activity (DPPIV) in blood and pleural fluid as possible markers for malignant pleural mesothelioma (MPM). It included 80 MPM patients treated between 1998 and 2013, 79 people with past asbestos exposure and pleural plaques, and 134 patients with other benign pleural diseases. Serum was available from 41 MPM patients and pleural fluid from 65. Serum sCD26 and DPPIV activity were significantly lower in MPM patients than in the asbestos-exposed group. For serum sCD26 the area under the ROC curve was 0.775 (95% CI, 0.682–0.868). At a cutoff of 1.00 mg/ml, sensitivity was 74.7% and specificity 71.4%. Serum sCD26 was lower in stage III and IV disease than in stage I and II. Median survival was 15.0 months (95% CI, 8.1–21.9) for MPM patients with serum DPPIV activity of 17.0 mM/min or more, versus 11.4 months (95% CI, 7.8–15.0) below that cutoff. In pleural fluid, both measures were higher in epithelioid MPM than in benign pleural disease. The authors concluded these might be useful diagnostic or prognostic markers, needing further validation.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Clinical biomarker study comparing blood and pleural fluid measurements between patient groups, with survival analysis in MPM patients
• Who was studied: 80 malignant pleural mesothelioma patients diagnosed and treated at Okayama Rosai Hospital and National Hospital Organization Yamaguchi-Ube Medical Center, Japan, between 1998 and 2013. Also 79 subjects with past asbestos exposure and pleural plaques on chest CT, and 134 patients with other benign pleural diseases as a control group. Serum was collected from 41 of the 80 MPM patients and from all asbestos-exposed subjects. Pleural fluid was collected from 65 of the 80 MPM patients and from all patients with other pleural diseases.
• Exposure: The study measured biomarkers, not asbestos exposure itself. Of the 80 MPM patients, 75 had an occupational history of asbestos exposure, with a median duration of 34 years. The comparison group had past asbestos exposure, with a median duration of 23 years, and pleural plaques. No fiber types are given.
• Main results:
  • Serum sCD26 was significantly lower in MPM patients than in subjects with past asbestos exposure. For telling these two groups apart, the AUC was 0.775 (95% CI, 0.682–0.868). At a cutoff of 1.00 mg/ml, sensitivity was 74.7% and specificity was 71.4%.
  • Serum DPPIV enzyme activity was significantly lower in MPM patients than in subjects with past asbestos exposure. The AUC was 0.778 (95% CI, 0.690-0.865). At a cutoff of 17.0 mM/min, sensitivity was 52.4% and specificity was 82.3%.
  • Among MPM patients, serum sCD26 was significantly lower in stage III and IV than in stage I and II (P = 0.047). DPPIV activity did not differ by stage (P = 0.333).
  • MPM patients with higher serum DPPIV activity (17.0 mM/min or more) had a median overall survival of 15.0 months (95% CI, 8.1–21.9). Those with lower activity had 11.4 months (95% CI, 7.8–15.0) (P = 0.032). Survival did not differ by serum sCD26 level (P = 0.660).
  • In pleural fluid, sCD26 (P = 0.012) and DPPIV activity (P = 0.009) were significantly higher in MPM patients with the epithelioid subtype than in patients with other pleural diseases. Pleural fluid sCD26 was also higher in epithelioid than in sarcomatous MPM (P = 0.040).
  • Survival did not differ by pleural fluid sCD26 alone (P = 0.260) or DPPIV activity alone (P = 0.582). However, MPM patients with lower specific DPPIV activity (DPPIV divided by sCD26) in pleural fluid lived longer: median survival 18.5 months versus 12.2 months for those with higher specific activity (P = 0.028).
  • For comparison, serum SMRP (another marker) distinguished MPM from past-exposure subjects with an AUC of 0.738 (95% CI, 0.638–0.838).
• The authors' conclusion: The authors concluded that serum sCD26 or DPPIV activity might be useful as early diagnostic or prognostic markers in MPM, or as a screening tool among people with past asbestos exposure. They also concluded that pleural fluid sCD26 could be a diagnostic marker of epithelioid MPM, and that further validation studies are essential.
• Limitations the authors state:
  • Serum data were missing for many MPM patients, because the study began with pleural fluid measurements and serum analyses were added later.
  • The authors stated that marker comparisons need a unified control group in future studies.
  • The authors noted that markers which decrease in disease have generally been difficult to use clinically.
  • Further validation studies are needed.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer, Mesothelioma.

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, Glycoprotein, Asbestos Exposure, Epithelioid, Biomarker, Prognosis.

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• Characterization of cancer stem cell properties of CD24 and CD26-positive human malignant mesothelioma cells — H. Yamazaki, M. Naito, et al. (2012)
• CD26/DPP4 - a potential biomarker and target for cancer therapy — N. Enz, G. Vliegen, et al. (2019)
• Clinical significance of serum vascular endothelial growth factor in malignant pleural mesothelioma — A. Yasumitsu, C. Tabata, et al. (2010)
• Clinical significance of epithelial-mesenchymal transition-associated markers in malignant pleural mesothelioma — T. Iwanami, H. Uramoto, et al. (2014)

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