title: Identification of proteomic signatures associated with lung cancer and COPD.
abstract: Lung cancer (LC) and chronic obstructive pulmonary disease (COPD) commonly coexist in smokers, and the presence of COPD increases the risk of developing LC. The aim of this study was to identify distinct proteomic profiles able to discriminate these two pathological entities. Protein content was assessed in the bronchoalveolar lavage (BAL) of 60 patients classified in four groups: COPD, COPD and LC, LC without COPD, and control with neither COPD nor LC. Proteins were separated into spots by bidimensional polyacrylamide gel electrophoresis (2D-PAGE) and examined by matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF/TOF). A total of 40 proteins were differentially expressed in the LC and/or COPD groups as compared with the control group. Distinct protein profiles were identified and validated for each pathological entity (LC and COPD). The main networks involved were related to inflammatory signalling, free radical scavenging and oxidative stress response, and glycolysis and gluconeogenesis pathways. The most relevant signalling link between LC and COPD was through the NF-κB pathway. In conclusion, the protein profiles identified contribute to elucidate the underlying pathogenic pathways of both diseases, and provide new tools of potential use as biomarkers for the early diagnosis of LC.
  
  
  CONCLUSIONS
  Sequence coverage. The protein sequence coverage (95%) was estimated for specific proteins by the percentage of matching amino acids from the identified peptides having confidence greater than or equal to 95% divided by the total number of amino acids in the sequence. Ingenuity Pathways Analysis. Mapping of our proteins onto biological pathways and disease networks demonstrated that 22 proteins were linked to inflammatory signalling (p-value: 1.35 10(-08)-1.42 10(-02)), 15 proteins were associated with free radical scavenging and oxidative stress response (p-value: 4.93 10(-11)-1.27 10(-02)), and 9 proteins were related with glycolysis and gluconeogenesis pathways (p-value: 7.39 10(-09)-1.58 10(-02)).
authors.affiliation: Instituto de Biomedicina de Sevilla (IBIS), (HUVR, CSIC, Universidad de Sevilla), Sevilla, Spain.
authors.forename: M D
authors.initials: MD
authors.lastname: Pastor
authors.forename: A
authors.initials: A
authors.lastname: Nogal
authors.forename: S
authors.initials: S
authors.lastname: Molina-Pinelo
authors.forename: R
authors.initials: R
authors.lastname: Meléndez
authors.forename: A
authors.initials: A
authors.lastname: Salinas
authors.forename: M
authors.initials: M
authors.lastname: González De la Peña
authors.forename: J
authors.initials: J
authors.lastname: Martín-Juan
authors.forename: J
authors.initials: J
authors.lastname: Corral
authors.forename: R
authors.initials: R
authors.lastname: García-Carbonero
authors.forename: A
authors.initials: A
authors.lastname: Carnero
authors.forename: L
authors.initials: L
authors.lastname: Paz-Ares
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D015180:Electrophoresis, Gel, Two-Dimensional; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism*; D040901:Proteomics; D029424:Pulmonary Disease, Chronic Obstructive / Q000378:metabolism* / Q000473:pathology; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins
keywords: 2D-PAGE; AKR1B10; AKR1C3; ALDH3A1; ALDOA; AMY1A; AMY2A; ANXA1; ANXA2; ANXA5; ARHGDIB; Aldehyde dehydrogenase 3 family, member A1; Aldo-keto reductase family 1, member B10; Aldo-keto reductase family 1, member C3; Aldolase A; Alpha 1 amylase; Alpha 2 amylase; Alpha enolase; Annexin A1; Annexin A2; Annexin A5; BAL; Biomarker; Bronchoalveolar lavage; Bronchoalveolar lavage fluid; C-reactive protein; C3A; CA1; CAPS; CAT; CFL1; COPD; CRP; CTSD; Calcyphosine; Carbonic anhydrase 1; Catalase; Cathepsin D; Chronic obstructive pulmonary disease; Cofilin 1; Complement C3; ENO1; EZR; Ezrin; FBP1; Fructose-1,6-bisphosphatase 1; GSR; GSTA1; GSTA2; GSTP; Glutathione S-transferase alpha 1; Glutathione S-transferase alpha 2; Glutathione S-transferase pi 1; Glutathione reductase; Glycogen phosphorylase; HSP70; Heat shock protein 70; IDH1; IPA; Inflammation; Ingenuity Pathways Analysis; Inhibitor of κB; Isocitrate dehydrogenase 1; IκB; LC; LCN2; Lipocalin 2; Lung cancer; MALDI-TOF/TOF; MMP; Matrix metalloproteinase; Matrix-assisted laser desorption/ionization time of flight-time of flight mass spectrometry; NF-κB; NSCLC; Non-small cell lung cancer; Nuclear factor κB; PEBP4; PKM2; PPIA; PRDX1; PRDX2; PRDX5; PYGM; Peptidylprolyl isomerase A (cyclophilin A); Peroxiredoxin 1; Peroxiredoxin 2; Peroxiredoxin 5; Phosphatidylethanolamine-binding protein 4; Proteomic; Pyruvate kinase 2; Rho GDP dissociation inhibitor beta; SCC; SELENBP1; SERPINB1; Selenium binding protein 1; Serpin peptidase inhibitor, clade B, member 1 (leukocyte elastase inhibitor); Squamous cell carcinoma; TKT; TPPP3; TXN; Thioredoxin; Transketolase; Tubulin polymerization-promoting protein family member 3 (CGI-38); Two dimensional electrophoresis