Peroxiredoxins and tropomyosins as plasma biomarkers for lung cancer and asbestos exposure

Our plain-English summary of Peroxiredoxins and tropomyosins as plasma biomarkers for lung cancer and asbestos exposure, by A. Rostila, A. Puustinen, T. Toljamo, et al (Lung Cancer, 2012).

The study

• Authors: A. Rostila, A. Puustinen, T. Toljamo, K. Vuopala, I. Lindström, T.A. Nyman, P. Oksa, T. Vehmas, S.L. Anttila
• Journal: Lung Cancer
• Published: 2012;77(2):450-9
• Cited by: 30 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

The prognosis of lung cancer is poor due to late diagnosis, the lack of established screening programs, and the paucity of early biomarkers for high-risk populations. Plasma proteome analysis was used to identify novel biomarkers for diagnosing lung cancer, and to unravel the mechanisms of underlying pathogenesis. Plasma proteins obtained from asbestos-exposed lung cancer cases detected by CT screening, asbestos-exposed subjects, clinical lung cancer patients, and healthy tobacco smokers, 5-6 cases in each group, were separated by two-dimensional gel electrophoresis, and identified with tandem mass spectrometry (LC-MS/MS). Nine proteins were selected for immunological confirmation in a test or validation set of plasma samples from an additional 49 clinical lung cancer cases, 66 asbestos-exposed patients, and 107 healthy tobacco smokers. Twenty-eight unique proteins were differentially expressed between the four study groups (p<0.05). Peroxiredoxin 1 (PRX1) was detected as a novel plasma marker for lung cancer (p=0.001). We also confirmed the previously found association of serum amyloid A with lung cancer (p<0.001). High plasma levels of tropomyosin 4 (TPM4: p<0.001) and peroxiredoxins 1 and 2 (PRX2: p<0.001) correlated with asbestos exposure or a diagnosis of asbestosis. PRX1 and PRX2 exhibited an inverse correlation with tobacco smoking (p<0.001). Plasma peroxiredoxins 1 and 2, and tropomyosin 4 were shown to associate with asbestos-exposure, and peroxiredoxin 1 with lung cancer. High plasma levels of peroxiredoxin 1 may result from genetic damage caused by reactive oxygen species. This study has identified several biomarkers worthy of further investigation in lung cancer and asbestos-related diseases.

Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

In plain English

This Finnish study looked for blood plasma proteins that might mark lung cancer or asbestos exposure. All participants were current or former smokers. First, plasma from 23 men in four groups was compared: asbestos-exposed men with lung cancer found by CT screening, asbestos-exposed men, lung cancer patients without significant asbestos exposure, and healthy smokers. Twenty-eight distinct proteins differed between groups. Selected proteins were then measured in a test set of 40 people and a validation set of 205 (60 asbestos-exposed, 46 with lung cancer, 99 healthy smokers). Peroxiredoxin 1 (PRX1) showed a strong correlation with lung cancer; its levels did not seem to be associated with cancer type or stage. Peroxiredoxin 2 (PRX2) was associated with asbestos exposure rather than lung cancer. Tropomyosin 4 (TPM4) correlated with asbestosis, but exposure and asbestosis could not be reliably separated. Both peroxiredoxins were inversely correlated with smoking. Serum amyloid A was high in most lung cancer cases but was not specific. The authors called for further study. They noted that never-smokers were excluded and that follow-up was too short to detect new cancers.

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: Plasma protein (proteomics) biomarker study. Two-dimensional gel electrophoresis and mass spectrometry were used in a small training set, followed by immunological (Western blot) confirmation in a test set and a validation set.
• Who was studied: Subjects were recruited from two institutions in Finland. Asbestos-exposed lung cancer patients came from a CT-screening health survey of asbestos-exposed workers (2003–2004). Asbestos-exposed patients without lung cancer were seen at an occupational medicine clinic (2006–2008). Clinical lung cancer patients came from Lapland Central Hospital (2003–2009). Healthy smokers with more than 20 pack years were recruited 2003–2005. All were current or former smokers. The groups were: training set n = 23 (all male; 5, 6, 6 and 6 per group); test set n = 40 (includes the training set); validation set n = 205 (60 asbestos-exposed, all male; 46 lung cancer, 37 male and 9 female; 99 healthy smokers, 58 male and 41 female). Lung cancer patients and healthy smokers were evaluated to ensure they had not been significantly exposed to asbestos.
• Exposure: Occupational asbestos exposure, with probability and intensity judged by specialists from work history; subjects with definite or probable exposure counted as exposed. No fiber type was specified. In the validation set's asbestos-exposed group, the table lists 23 with asbestosis and 37 with pleural plaques. Tobacco smoking was also analysed.
• Main results:
  • In the initial screening of 23 samples, 36 protein spots and 28 distinct proteins differed between the four groups.
  • In the validation set, PRX1 showed a strong correlation with lung cancer; neither cancer type nor stage seemed to be associated with PRX1 levels.
  • In multiple regression of PRX1 by group, age and smoking factors, the most significant association was with the lung cancer group (p less than 0.001).
  • In the test set, PRX1 over-expression was seen in all groups with lung cancer and in the asbestos-exposed group.
  • PRX2 was associated with asbestos exposure rather than with lung cancer.
  • PRX1 and PRX2 were inversely correlated with tobacco smoking (p less than 0.001).
  • Higher TPM4 levels also correlated with asbestosis.
  • Both tropomyosins (TPM3 and TPM4) were lower in lung cancer patients, especially at stage IV.
  • Serum amyloid A was over-expressed in lung cancer patients but was not specific as a marker.
• The authors' conclusion: The authors concluded that PRX1 and serum amyloid A were raised in lung cancer patients, while high PRX2, TPM3 and TPM4 levels were associated with asbestos exposure. They proposed further investigation of these proteins as early diagnosis markers of lung cancer.
• Limitations the authors state:
  • Only current or former smokers were studied. The authors state that excluding never-smokers is a potential bias.
  • Follow-up of the asbestos-exposed individuals was too short to detect new cancer cases.
  • The associations of TPM4 with asbestos exposure and with asbestosis could not be separated reliably.
  • For asbestos-exposed people who developed lung cancer, the authors could not determine whether smoking or asbestos started the cancer process.

Topics

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

Medical terms in this study, explained in our Lexicon: Biomarker, Lung Cancer, Asbestos Exposure, Prognosis, Reactive Oxygen Species (ROS).

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