Serum concentration of integrin-linked kinase in malignant pleural mesothelioma and after asbestos exposure

Our plain-English summary of Serum concentration of integrin-linked kinase in malignant pleural mesothelioma and after asbestos exposure, by S.B. Watzka, F. Posch, H.I. Pass, et al (European Journal of Cardio-thoracic Surgery, 2013).

The study

• Authors: S.B. Watzka, F. Posch, H.I. Pass, R.M. Flores, G.E. Hannigan, D. Bernhard, M. Weber, M.R. Mueller
• Journal: European Journal of Cardio-thoracic Surgery
• Published: 2013;43(5):940-5
• Cited by: 7 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Objectives: Integrin-linked kinase (ILK) is an intracellular protein implicated in chronic inflammation and neoplastic transformation. In a recently accomplished pilot study, we showed that ILK can be detected in the serum of patients with benign and malignant chest diseases, including malignant pleural mesothelioma (MPM). Interestingly, average serum ILK concentrations were 10 times higher in MPM patients when compared with the rest of the study population, and a diagnostic test solely based on serum ILK concentration could discriminate between MPM and non-MPM with considerable accuracy. This study aimed to investigate whether serum ILK concentration could also be used to discriminate between MPM and asbestos exposure only.

Methods: Using a self-developed sandwich enzyme-linked immunosorbent assay, we measured serum ILK concentrations in 101 MPM patients, and 96 asbestos-exposed, but healthy insulation workers. Seventy-three MPM patients had an epitheloid subtype (72.3%), and 42 had a Stage I or II disease (41.6%).

Results: When compared with asbestos-exposed individuals, MPM patients of all clinical stages had significantly higher (mean ± standard deviation, median) serum ILK concentrations (10.7 ± 13.6, median 7 ng/ml vs 3.1 ± 4.6, median 1.4 ng/ml; P < 0.001). Among MPM patients, the serum ILK concentration was significantly higher at advanced disease stages III + IV than at early stages I + II (13.7 ± 15.9, median 8.5 ng/ml vs 6.7 ± 7.8, median 3.5 ng/ml; P = 0.02). Using serum ILK to discriminate between MPM patients and asbestos-exposed individuals yielded an area under the curve of 0.69 (95% confidence interval 0.63-0.76). The corresponding sensitivity and specificity for a cut-off of 4.49 ng/ml ILK are 61.4 and 80.2%, respectively.

Conclusions: These data show significant differences between MPM patients and asbestos-exposed but healthy individuals concerning their serum ILK concentration. Furthermore, since ILK levels are increased in advanced MPM stages in comparison with early MPM stages, we suggest evaluating its potential use as a marker of disease progression in MPM.

In plain English

This study measured a protein called integrin-linked kinase (ILK) in stored blood serum. The aim was to see whether it could tell malignant pleural mesothelioma (MPM) apart from asbestos exposure alone. The authors tested frozen samples from 101 MPM patients and 96 asbestos-exposed insulation workers whose chest CT scans showed no MPM, using a laboratory test they had developed themselves. The article does not say which fiber types the workers encountered. Average ILK was 10.7 ng/ml (median 7) in MPM patients and 3.1 ng/ml (median 1.4) in the workers, P less than 0.001. Among MPM patients, levels were higher at stages III and IV than at stages I and II (median 8.5 versus 3.5 ng/ml, P = 0.02). A cut-off of 4.49 ng/ml correctly identified 62 of 101 MPM patients and correctly cleared 77 of 96 workers. The workers were younger than the patients and all were male. The authors concluded that ILK levels differed significantly between the groups and suggested studying ILK as a marker of disease progression. They noted the test's modest sensitivity, and that MPM was far more common in their sample than in real at-risk groups.

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 comparison of stored (frozen) serum samples from mesothelioma patients and asbestos-exposed healthy workers, measured with the authors' own ELISA test; lab staff were blinded to patient identity and condition
• Who was studied: Serum samples from a thoracic surgical tissue bank at NYU Langone Medical Center (USA), analysed in Vienna, Austria: 101 patients with malignant pleural mesothelioma (73 epitheloid subtype; 42 at stage I or II, 59 at stage III or IV) and 96 asbestos-exposed but healthy insulation workers, all male. Collection dates are not given.
• Exposure: Occupational asbestos exposure in insulation workers. The article does not give the fiber type or dose for these workers. Workers had a chest CT that excluded MPM before blood was drawn.
• Main results:
  • MPM patients (all stages) had higher serum ILK than asbestos-exposed workers: mean 10.7 plus or minus 13.6, median 7 ng/ml, versus 3.1 plus or minus 4.6, median 1.4 ng/ml; P less than 0.001.
  • Among MPM patients, serum ILK was higher at stages III and IV (13.7 plus or minus 15.9, median 8.5 ng/ml) than at stages I and II (6.7 plus or minus 7.8, median 3.5 ng/ml); P = 0.02.
  • A cut-off of 4.49 ng/ml separated MPM (all stages) from asbestos exposure with sensitivity 61.4% (62 of 101 MPM patients) and specificity 80.2% (77 of 96 workers); area under the curve 0.69 (95% confidence interval 0.63 to 0.76).
  • No significant differences in serum ILK were found by histological subtype of MPM (P = 0.7), and gender had no statistical impact (P = 0.245).
  • The asbestos-exposed workers were significantly younger than both MPM stage groups (mean age 57.8 versus 66.1 and 62.8 years) and were all male.
• The authors' conclusion: The authors concluded that serum ILK differed significantly between MPM patients and asbestos-exposed but healthy individuals. Because levels were higher in advanced than in early stages, they suggested evaluating ILK as a possible marker of disease progression in MPM.
• Limitations the authors state:
  • The test's sensitivity for early MPM detection was modest.
  • Because all asbestos-exposed workers were male, the authors could not model an interaction between group and gender.
  • MPM made up about half of their sample, much more than in a real at-risk population. In their sample this gave a positive predictive value of 76% and a negative predictive value of 66%. At an estimated 5% prevalence the positive predictive value would fall to 14% and the negative predictive value would rise to 96%.
  • The normal serum ILK level, and other processes that may release ILK into the blood, are unknown.
  • Clinical stage is only a rough approximation of tumour burden.

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, Asbestos Exposure, Chronic Inflammation, Insulator, confidence interval, Disease Progression.

Related studies

• Detection of integrin-linked kinase in the serum of patients with malignant pleural mesothelioma — S.B. Watzka, F. Posch, et al. (2011)
• Integrin-linked kinase, phosphorylated AKT and the prognosis of malignant pleural mesothelioma — S.B. Watzka, U. Setinek, et al. (2011)
• 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)
• 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)
• Soluble mesothelin-related peptide level elevation in mesothelioma serum and pleural effusions — H.I. Pass, A. Wali, et al. (2008)

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