title: Peroxiredoxins and tropomyosins as plasma biomarkers for lung cancer and asbestos exposure.
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.
authors.affiliation: Department of Pathology, HUSLAB and Helsinki University Hospital, Helsinki and Espoo, P.O. 800, FI-00029 HUS, Finland.
authors.forename: Annina
authors.initials: A
authors.lastname: Rostila
authors.forename: Anne
authors.initials: A
authors.lastname: Puustinen
authors.forename: Tuula
authors.initials: T
authors.lastname: Toljamo
authors.forename: Katri
authors.initials: K
authors.lastname: Vuopala
authors.forename: Irmeli
authors.initials: I
authors.lastname: Lindström
authors.forename: Tuula A
authors.initials: TA
authors.lastname: Nyman
authors.forename: Panu
authors.initials: P
authors.lastname: Oksa
authors.forename: Tapio
authors.initials: T
authors.lastname: Vehmas
authors.forename: Sisko L
authors.initials: SL
authors.lastname: Anttila
mesh_terms: D000368:Aged; D001194:Asbestos / Q000633:toxicity*; D014408:Biomarkers, Tumor / Q000097:blood*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000097:blood* / Q000209:etiology*; D008297:Male; D008875:Middle Aged; D016273:Occupational Exposure; D054464:Peroxiredoxins / Q000097:blood*; D000685:Serum Amyloid A Protein / Q000378:metabolism; D014335:Tropomyosin / Q000097:blood*
chemical_list: D014408:Biomarkers, Tumor; D000685:Serum Amyloid A Protein; D014335:Tropomyosin; D001194:Asbestos; D054464:Peroxiredoxins