Comparative proteomic analysis of malignant pleural mesothelioma evidences an altered expression of nuclear lamin and filament-related proteins

Our plain-English summary of Comparative proteomic analysis of malignant pleural mesothelioma evidences an altered expression of nuclear lamin and filament-related proteins, by L. Giusti, Y. Da Valle, A. Bonotti, et al (Proteomics. Clinical Applications, 2014).

The study

• Authors: L. Giusti, Y. Da Valle, A. Bonotti, E. Donadio, F. Ciregia, T. Ventroni, R. Foddis, G. Giannaccini, G. Guglielmi, A. Cristaudo, A. Lucacchini
• Journal: Proteomics. Clinical Applications
• Published: 2014;8(3-4):258-68
• Cited by: 19 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Purpose: Malignant mesothelioma is a neoplastic disease linked to asbestos exposure whose diagnosis is limited, so detection methods for an early diagnosis and treatment result essential. Here, we compared proteomic profiles of malignant pleural mesothelioma (MPM) and benign biopsies to search potential biomarkers useful in differential diagnosis.

Experimental Design: Tissue biopsies were obtained from 53 patients who were subjected to a diagnostic thoracoscopy. 2DE/MS based approach was used for proteomic analysis and protein validation was carried out by Western blot analysis versus benign and lung carcinoma samples.

Results: Among the proteins identified we confirmed known MPM biomarkers such as calretinin and suggested the new ones as prelamin A/C, desmin, vimentin, calretinin, fructose-bisphosphate aldolase A, myosin regulatory light chain 2, ventricular/cardiac muscle isoform, myosin light chain 3 and myosin light chain 6B. Ingenuity software was used to identify the biological processes to which these proteins belong and to construct a potential network.

Conclusions And Clinical Relevance: Overall, our results suggest potential biomarkers that can be useful in occupational medicine for the early identification of the onset of disease in health surveillance of past asbestos-exposed workers, for monitoring the progress of disease and for assessing the response to treatment.

© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

In plain English

This prospective laboratory study compared the proteins found in pleural tissue biopsies taken during diagnostic thoracoscopy from 53 patients. There were 22 with epithelioid malignant pleural mesothelioma (MPM), 11 with benign conditions (six pleural inflammation, five hyperplasia) and 20 with lung carcinoma. Asbestos exposure was recorded for 13 mesothelioma patients (59%), 7 benign (63%) and 11 carcinoma (55%). The article did not name fiber types or analyze exposure. Using pooled samples from ten mesothelioma and ten benign patients, the authors identified 30 proteins with at least threefold differences. Testing in all samples confirmed that three proteins, prelamin A/C, vimentin and calretinin, were higher in mesothelioma. Five others, desmin, ALDOA and three myosin light chains, were lower. This held against both benign tissue and lung carcinoma. In separating mesothelioma from lung carcinoma, calretinin had sensitivity 0.71 and specificity 0.86. Prelamin A/C had similar sensitivity (around 0.7) and specificity 0.95. The authors concluded these were potential biomarkers that could help diagnosis and might be used in health surveillance of past asbestos-exposed workers.

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: Prospective comparative proteomic study of tissue biopsies (2D gel electrophoresis with mass spectrometry, followed by Western blot validation, ROC analysis and pathway software analysis)
• Who was studied: 53 patients who had diagnostic thoracoscopy, enrolled at diagnosis before any treatment. Histology showed 22 epithelioid MPM (20 male, 2 female; median age 64.5), 11 benign (6 pleural inflammation, 5 hyperplasia) used as negative controls, and 20 lung carcinoma (10 adenocarcinoma, 10 squamous cell carcinoma) used as positive controls. The authors were based at the University of Pisa and the Hospital of Pisa, Italy. Enrollment dates were not given.
• Exposure: Asbestos exposure was not the subject of analysis. Table 1 records asbestos exposure in 13 (59%) of the 22 mesothelioma patients, 7 (63%) of the 11 benign controls and 11 (55%) of the 20 lung carcinoma patients. No fiber types, products, jobs or doses are given.
• Main results:
  • In pooled samples (10 MPM vs 10 benign), 114 protein spots differed by at least twofold. The 37 spots differing by at least threefold were identified as 30 different proteins.
  • Western blot comparing all 22 MPM with 11 benign samples confirmed higher prelamin A/C, vimentin and calretinin in MPM (p = 0.0247, 0.0123 and 0.0376). It also confirmed lower desmin, ALDOA, MYL6B, MYL3 and MYL2 (p = 0.0434, 0.0236, 0.0282, 0.0401 and 0.0335).
  • Compared with 20 lung carcinoma samples, MPM showed higher prelamin A/C (p < 0.0001), vimentin (p = 0.0001) and calretinin (p = 0.0003). It showed lower desmin (p = 0.0103), ALDOA (p = 0.0452), MYL6B (p = 0.0169), MYL3 (p = 0.0048) and MYL2 (0.0247).
  • Between benign and carcinoma samples there was no statistically significant difference for any protein except prelamin A/C and MYL6B.
  • For distinguishing MPM from lung carcinoma, calretinin had sensitivity 0.71 and specificity 0.86. Prelamin A/C and vimentin had sensitivity around 0.7, and prelamin A/C had specificity 0.95.
  • For MPM versus all controls (cancerous and noncancerous), sensitivity and specificity were reduced, but the AUC values for calretinin and prelamin A/C were always greater than 0.7.
  • Pathway software analysis of 22 proteins produced a network with a score of 34 that included 16 of the 22 proteins.
• The authors' conclusion: The authors concluded that their results suggest new potential biomarkers which, added to those previously identified, could form a panel useful in the differential diagnosis of MPM. They added that these could be applied in occupational medicine for early identification of disease onset in health surveillance of past asbestos-exposed workers.
• Limitations the authors state:
  • The authors note that the number of tissue samples was constrained by how common the disease is and by the use of thoracoscopy as the diagnostic tool.

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, Malignant Mesothelioma, Asbestos Exposure, Biomarker, Differential Diagnosis, Thoracoscopy, Carcinoma, Calretinin.

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