Detection of integrin-linked kinase in the serum of patients with malignant pleural mesothelioma

Our plain-English summary of Detection of integrin-linked kinase in the serum of patients with malignant pleural mesothelioma, by S.B. Watzka, F. Posch, H.I. Pass, et al (The Journal of Thoracic and Cardiovascular Surgery, 2011).

The study

• Authors: S.B. Watzka, F. Posch, H.I. Pass, M. Huflejt, D. Bernhard, G.E. Hannigan, M.R. Müller
• Journal: The Journal of Thoracic and Cardiovascular Surgery
• Published: 2011;142(2):384-9
• Cited by: 12 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Objective: Integrin-linked kinase, which is relevant to neoplastic transformation, is highly expressed in malignant pleural mesothelioma. Recently, detection of integrin-linked kinase in serum of patients with ovarian cancer has been reported. This study asks whether integrin-linked kinase can also be detected in serum of patients with malignant pleural mesothelioma and whether serum level has diagnostic or prognostic relevance for that disease.

Methods: A sandwich enzyme-linked immunosorbent assay was designed to detect integrin-linked kinase and applied to serum samples from 46 patients with malignant pleural mesothelioma, 98 patients with other malignant chest disease, and 23 patients with benign chest disease. Integrin-linked kinase serum concentration and clinical data were correlated statistically.

Results: Median serum integrin-linked kinase concentration was significantly higher in malignant pleural mesothelioma (8.89 ng/mL) than in other malignant chest disease (0.66 ng/mL) or benign chest disease (0.78 ng/mL, P < .001). There was no relevant correlation of serum integrin-linked kinase with cell lysis parameters (R(2) < 0.1). Serum integrin-linked kinase concentration greater than 2.48 ng/mL had diagnostic sensitivity of 80%, specificity of 95%, positive predictive value of 85.7%, negative predictive value of 92.7%, and overall accuracy of 91% for distinction between malignant pleural mesothelioma and other diseases. Serum integrin-linked kinase concentration in malignant pleural mesothelioma was independent of histologic subtype or asbestos exposure. There was no statistically significant impact of serum integrin-linked kinase concentration on prognosis.

Conclusions: Integrin-linked kinase can be detected in serum of patients with malignant pleural mesothelioma and may be a diagnostic marker for the disease.

Copyright © 2011 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.

In plain English

This study asked whether a protein called integrin-linked kinase (ILK) can be measured in the blood serum of patients with malignant pleural mesothelioma (MPM), and whether it helps with diagnosis or with predicting survival. The authors designed a test and applied it to stored serum from patients in New York and Vienna. After one suspect MPM sample was excluded, 45 patients with MPM, 98 with other malignant chest disease and 23 with benign chest disease were analyzed. Median serum ILK was 8.89 ng/mL in the MPM group, compared with 0.66 ng/mL and 0.78 ng/mL in the two other groups. Above a cutoff of 2.48 ng/mL, the test flagged 36 of 45 MPM patients (sensitivity 80%) and correctly cleared 115 of 121 others (specificity 95%). Among MPM patients, ILK levels did not differ significantly by asbestos exposure, subtype or stage, and had no statistically significant effect on survival. The authors concluded that ILK may be a diagnostic marker for MPM. They noted that their survival analysis had low statistical power and that the normal ILK value is unknown.

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: Laboratory diagnostic (biomarker) study comparing stored serum samples from patients with MPM against two control groups, with follow-up of the MPM patients for survival
• Who was studied: Frozen serum from tissue banks at NYU Langone Medical Center (New York) and Otto Wagner Hospital (Vienna). The samples came from 46 patients with MPM, drawn at the time of surgery, plus 98 treatment-naive patients with other malignant chest disease and 23 treatment-naive patients with benign chest disease. One MPM sample was excluded as a suspected technical error, leaving 166 patients analyzed. Follow-up data ran to November 2010.
• Exposure: The main factor measured was serum ILK concentration, using a newly designed sandwich enzyme-linked immunosorbent assay. Asbestos exposure was recorded by interview for the MPM patients only: 73.3% were exposed and 26.7% were not. No fiber types or doses were reported.
• Main results:
  • Median serum ILK was 8.89 ng/mL in MPM patients, significantly higher than in patients with other malignant chest disease (0.66 ng/mL) or benign chest disease (0.78 ng/mL), P<.001
  • Serum ILK did not differ statistically between patients with other malignant chest disease and those with benign chest disease
  • A cutoff above 2.48 ng/mL separated MPM from the other diseases with sensitivity 80%, specificity 95%, positive predictive value 85.7%, negative predictive value 92.7% and overall accuracy 91%. The area under the curve was 89.1% (95% confidence interval 82% to 96.1%).
  • At the 2.48 ng/mL threshold, 36 of 45 MPM patients tested positive, and 115 of 121 patients without MPM tested negative
  • Among MPM patients, serum ILK did not differ significantly by asbestos exposure, histologic subtype, combined clinical stage, disease progression or survival. For asbestos exposure, mean ILK was 11 ng/mL in unexposed and 10.71 ng/mL in exposed patients, P = .8.
  • In the multivariate survival model for MPM patients, serum ILK had no statistically significant effect on survival (hazard ratio 1.006, P = .8). Only combined stage was significant: stage I and II patients lived longer (hazard ratio 0.205, P = .002).
  • Serum ILK showed no relevant correlation with the cell lysis markers creatine kinase, lactate dehydrogenase, aspartate aminotransferase and alanine aminotransferase (R2 below 0.1)
• The authors' conclusion: The authors concluded that ILK can be detected in the serum of patients with malignant pleural mesothelioma and may be a diagnostic marker for the disease
• Limitations the authors state:
  • Because serum ILK values varied so much, the authors said statistical power for the prognosis analysis was low and a much larger study is needed before definitive conclusions
  • Because of the small sample size, the lack of a difference in ILK between early- and late-stage MPM must be interpreted with caution
  • The comparison group with other malignant chest disease included more early-stage cases than the MPM group
  • The normal value of serum ILK is unknown
  • How ILK gets into the bloodstream is not clear

Topics

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

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, Ovarian Cancer, Histological Subtype, Asbestos Exposure, Prognosis.

Related studies

• Serum concentration of integrin-linked kinase in malignant pleural mesothelioma and after asbestos exposure — S.B. Watzka, F. Posch, et al. (2013)
• Integrin-linked kinase, phosphorylated AKT and the prognosis of malignant pleural mesothelioma — S.B. Watzka, U. Setinek, et al. (2011)
• Development of an enzyme-linked immunosorbent assay for the detection of human calretinin in plasma and serum of mesothelioma patients — I. Raiko, I. Sander, et al. (2010)
• Sensitive and specific new enzyme-linked immunosorbent assay for N-ERC/mesothelin increases its potential as a useful serum tumor marker for mesothelioma — K. Shiomi, Y. Hagiwara, et al. (2008)
• beta1-integrin mediates asbestos-induced phosphorylation of AKT and ERK1/2 in a rat pleural mesothelial cell line — A. Berken, J. Abel, et al. (2003)
• Antiproliferative effect of Aurora kinase targeting in mesothelioma — S. Crispi, C. Fagliarone, et al. (2010)

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