Putative Biomarkers for Malignant Pleural Mesothelioma Suggested by Proteomic Analysis of Cell Secretome

Our plain-English summary of Putative Biomarkers for Malignant Pleural Mesothelioma Suggested by Proteomic Analysis of Cell Secretome, by S. Lacerenza, F. Ciregia, L. Giusti, et al (Cancer Genomics & Proteomics, 2020).

The study

• Authors: S. Lacerenza, F. Ciregia, L. Giusti, A. Bonotti, V. Greco, G. Giannaccini, V. D'Antongiovanni, P. Fallahi, L. Pieroni, A. Cristaudo, A. Lucacchini, M.R. Mazzoni, R. Foddis
• Journal: Cancer Genomics & Proteomics
• Published: 2020;17(3):225-236
• Cited by: 18 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background: Malignant pleural mesothelioma (MPM) a rare neoplasm linked to asbestos exposure is characterized by a poor prognosis. Soluble mesothelin is currently considered the most specific diagnostic biomarker. The aim of the study was to identify novel biomarkers by proteomic analysis of two MPM cell lines secretome.

Materials And Methods: The protein patterns of MPM cells secretome were examined and compared to a non-malignant mesothelial cell line using two-dimensional gel electrophoresis coupled to mass spectrometry. Serum levels of candidate biomarkers were determined in MPM patients and control subjects.

Results: Two up-regulated proteins involved in cancer biology, prosaposin and quiescin Q6 sulfhydryl oxidase 1, were considered candidate biomarkers. Serum levels of both proteins were significantly higher in MPM patients than control subjects. Combining the data of each receiver-operating characteristic analysis predicted a good diagnostic accuracy.

Conclusion: A panel of the putative biomarkers represents a promising tool for MPM diagnosis.

Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

In plain English

This Italian laboratory study looked for new blood markers of malignant pleural mesothelioma (MPM). The authors compared proteins inside two MPM cell lines (NCI-H2052 and NCI-H28) with those of a non-malignant mesothelial line (Met-5A), and set out to compare the proteins the cells released. Released proteins could be compared only for NCI-H2052, because too little protein was recovered from NCI-H28. From the NCI-H2052 cells, three over-produced released proteins were identified. Two of them, prosaposin (PSAP) and QSOX1, were measured in serum from 32 MPM patients, all epithelioid type, and 36 asbestos-exposed people without cancer. Both proteins were higher in the patients. Median PSAP was 495.32 ng/ml in patients versus 393.35 ng/ml in controls, and median QSOX1 was 8.70 versus 0.20 ng/ml. In separating patients from exposed controls, the area under the curve (AUC) was 0.75 for PSAP and 0.85 for QSOX1. For the two combined it was 0.95, with 92% specificity and 88% sensitivity. The authors concluded that a panel of these markers is a promising tool for MPM diagnosis. They said larger studies are needed to confirm the findings.

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 proteomic comparison of mesothelioma and non-malignant mesothelial cell lines, followed by measurement of two candidate proteins in serum from MPM patients and asbestos-exposed healthy controls. Proteins inside the cells were compared for both MPM lines. Released proteins were compared only for NCI-H2052.
• Who was studied: Two MPM cell lines (NCI-H28, NCI-H2052) and one non-malignant mesothelial cell line (Met-5A). Serum came from 32 MPM patients (all epithelioid, sampled at diagnosis before treatment) and 36 asbestos-exposed subjects without MPM or other cancer. Samples were collected at the Occupational Medicine Unit of the University-Hospital of Pisa from 2008 to 2016.
• Exposure: Asbestos exposure among the serum donors. No fiber types, products or doses are given. Table I lists asbestos exposure for 100% of controls and 93% of MPM patients. Mean years of work were 33 plus or minus 8 (controls) and 32 plus or minus 11 (patients).
• Main results:
  • Proteins inside the cells were compared with Met-5A for both MPM lines. For NCI-H2052, 20 spots were increased and 13 decreased by more than 2-fold. For NCI-H28, 270 spots differed significantly, with 9 increased and 9 decreased by more than 2-fold.
  • In NCI-H2052 cells compared with Met-5A cells, 91 released-protein spots differed. Of these, 7 were increased and 10 were decreased by more than 2-fold. NCI-H28 released proteins could not be analysed because of low protein amounts.
  • Three over-expressed proteins were identified among those released by NCI-H2052 cells (QSOX1, LDHA, PSAP). PSAP and QSOX1 were chosen as candidate biomarkers.
  • Serum PSAP and QSOX1 were significantly higher in MPM patients than in asbestos-exposed healthy subjects. Median PSAP was 393.35 ng/ml in exposed controls and 495.32 ng/ml in MPM patients (p=0.0002). Median QSOX1 was 0.20 ng/ml in exposed controls and 8.70 ng/ml in MPM patients (p less than 0.0001).
  • In distinguishing MPM patients (n=32) from asbestos-exposed healthy subjects (n=36), PSAP alone had an AUC of 0.75 (67% specificity, 75% sensitivity). QSOX1 alone had an AUC of 0.85 (86% specificity, 84% sensitivity).
  • Combining PSAP and QSOX1 by logistic regression gave an AUC of 0.95, with 92% specificity and 88% sensitivity, in the same patient and control groups.
• The authors' conclusion: The authors concluded that a panel of PSAP and QSOX1 is a promising tool for MPM diagnosis. They suggested it could be considered as a biomarker panel for screening asbestos-exposed subjects, pending confirmation in larger studies.
• Limitations the authors state:
  • Further studies on larger groups of patients and controls are needed to confirm the findings and to look at possible prognostic value.
  • The laboratory method used was less sensitive than other techniques, so few proteins were identified.
  • Half the amount of released-protein sample was used compared with an earlier study.
  • Proteins released by the NCI-H28 cell line could not be analysed because too little protein was recovered.
  • PSAP alone did not show very high specificity and sensitivity.

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: Biomarker, Pleural Mesothelioma, Neoplasm, Asbestos Exposure, Prognosis, Mesothelin, Mesothelial Cells.

Related studies

• A Proteomic Analysis of the Malignant Mesothelioma Secretome Using iTRAQ — J. Creaney, I.M. Dick, et al. (2017)
• A Novel Panel of Serum Biomarkers for MPM Diagnosis — A. Bonotti, R. Foddis, et al. (2017)
• Proteome screening of pleural effusions identifies galectin 1 as a diagnostic biomarker and highlights several prognostic biomarkers for malignant mesothelioma — F. Mundt, H.J. Johansson, et al. (2014)
• Comparative proteomic analysis of malignant pleural mesothelioma evidences an altered expression of nuclear lamin and filament-related proteins — L. Giusti, Y. Da Valle, et al. (2014)
• Comparative proteomic analysis of malignant pleural mesothelioma: Focusing on the biphasic subtype — L. Giusti, F. Ciregia, et al. (2016)
• Polymorphisms in the putative micro-RNA-binding sites of mesothelin gene are associated with serum levels of mesothelin-related protein — A. Cristaudo, R. Foddis, et al. (2010)

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