title: Elevated levels of the complement activation product C4d in bronchial fluids for the diagnosis of lung cancer.
abstract: Molecular markers in bronchial fluids may contribute to the diagnosis of lung cancer. We previously observed a significant increase of C4d-containing complement degradation fragments in bronchoalveolar lavage (BAL) supernatants from lung cancer patients in a cohort of 50 cases and 22 controls (CUN cohort). The present study was designed to determine the diagnostic performance of these complement fragments (hereinafter jointly referred as C4d) in bronchial fluids. C4d levels were determined in BAL supernatants from two independent cohorts: the CU cohort (25 cases and 26 controls) and the HUVR cohort (60 cases and 98 controls). A series of spontaneous sputum samples from 68 patients with lung cancer and 10 controls was also used (LCCCIO cohort). Total protein content, complement C4, complement C5a, and CYFRA 21-1 were also measured in all cohorts. C4d levels were significantly increased in BAL samples from lung cancer patients. The area under the ROC curve was 0.82 (95%CI = 0.71-0.94) and 0.67 (95%CI = 0.58-0.76) for the CU and HUVR cohorts, respectively. In addition, unlike the other markers, C4d levels in BAL samples were highly consistent across the CUN, CU and HUVR cohorts. Interestingly, C4d test markedly increased the sensitivity of bronchoscopy in the two cohorts in which cytological data were available (CUN and HUVR cohorts). Finally, in the LCCCIO cohort, C4d levels were higher in sputum supernatants from patients with lung cancer (area under the ROC curve: 0.7; 95%CI = 0.56-0.83). In conclusion, C4d is consistently elevated in bronchial fluids from lung cancer patients and may be used to improve the diagnosis of the disease.
authors: Program in Solid Tumors and Biomarkers, Center for Applied Medical Research (CIMA), Pamplona, Spain.
authors: Daniel
authors: D
authors: Ajona
authors: Program in Solid Tumors and Biomarkers, Center for Applied Medical Research (CIMA), Pamplona, Spain.
authors: Cristina
authors: C
authors: Razquin
authors: Laboratorio de Oncologia Molecular y Nuevas Terapias, Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocio/CSIC/Universidad de Sevilla, Sevilla, Spain.
authors: Maria Dolores
authors: MD
authors: Pastor
authors: Program in Solid Tumors and Biomarkers, Center for Applied Medical Research (CIMA), Pamplona, Spain; Department of Histology and Pathology, School of Medicine, University of Navarra, Pamplona, Spain.
authors: Maria Jose
authors: MJ
authors: Pajares
authors: Department of Pulmonary Medicine, Clinica Universidad de Navarra, Pamplona, Spain.
authors: Javier
authors: J
authors: Garcia
authors: Medical Oncology Department, Catalan Institute of Oncology-IDIBELL, Barcelona, Spain.
authors: Felipe
authors: F
authors: Cardenal
authors: Molecular Biology Laboratory, Universitätsklinikum Halle, Saale, Germany.
authors: Michael
authors: M
authors: Fleischhacker
authors: Department of Pathology, Clinica Universidad de Navarra, Pamplona, Spain.
authors: Maria Dolores
authors: MD
authors: Lozano
authors: Department of Pulmonary Medicine, Clinica Universidad de Navarra, Pamplona, Spain.
authors: Javier J
authors: JJ
authors: Zulueta
authors: Molecular Biology Laboratory, Universitätsklinikum Halle, Saale, Germany.
authors: Bernd
authors: B
authors: Schmidt
authors: Medical Oncology Department, Catalan Institute of Oncology-IDIBELL, Barcelona, Spain.
authors: Ernest
authors: E
authors: Nadal
authors: Laboratorio de Oncologia Molecular y Nuevas Terapias, Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocio/CSIC/Universidad de Sevilla, Sevilla, Spain.
authors: Luis
authors: L
authors: Paz-Ares
authors: Program in Solid Tumors and Biomarkers, Center for Applied Medical Research (CIMA), Pamplona, Spain; Department of Histology and Pathology, School of Medicine, University of Navarra, Pamplona, Spain.
authors: Luis M
authors: LM
authors: Montuenga
authors: Program in Solid Tumors and Biomarkers, Center for Applied Medical Research (CIMA), Pamplona, Spain; Department of Biochemistry and Genetics, School of Sciences, University of Navarra, Pamplona, Spain.
authors: Ruben
authors: R
authors: Pio
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis* / Q000378:metabolism; D000328:Adult; D000368:Aged; D000951:Antigens, Neoplasm / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry*; D001999:Bronchoscopy; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis* / Q000378:metabolism; D016022:Case-Control Studies; D015331:Cohort Studies; D003167:Complement Activation; D015935:Complement C4b / Q000378:metabolism*; D015936:Complement C5a / Q000378:metabolism; D005260:Female; D006801:Humans; D053539:Keratin-19 / Q000378:metabolism; D008175:Lung Neoplasms / Q000175:diagnosis* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D010446:Peptide Fragments / Q000378:metabolism*; D011379:Prognosis; D012372:ROC Curve; D055752:Small Cell Lung Carcinoma / Q000175:diagnosis* / Q000378:metabolism; D013183:Sputum / Q000378:metabolism
chemical_list: D000951:Antigens, Neoplasm; D015415:Biomarkers; D053539:Keratin-19; D010446:Peptide Fragments; C102012:antigen CYFRA21.1; D015935:Complement C4b; C032261:complement C4d; D015936:Complement C5a