Complement C4d-specific antibodies for the diagnosis of lung cancer

Daniel Ajona , Marcin Okrój , María J. Pajares , Jackeline Agorreta , María D. Lozano , Javier J. Zulueta , Carla Verri , Luca Roz , Gabriella Sozzi , Ugo Pastorino , Pierre P. Massion , Luis M. Montuenga , Anna M. Blom , Ruben Pio


Development of molecular markers that help to identify high-risk individuals or diagnose indeterminate pulmonary nodules could have a major impact on lung cancer clinical management. In this study, we evaluated the diagnostic potential of a newly-developed ELISA that specifically detects complement C4d. We measured this marker in five independent cohorts of plasma and bronchoalveolar lavage samples from lung cancer patients and controls. In case-control studies, the area under the ROC curve for the diagnosis of lung cancer was 0.82 (95%CI = 0.72–0.92) in plasma samples, and 0.80 (95%CI = 0.69 to 0.90) in bronchoalveolar lavage fluids. In a set of plasma samples from the MILD CT-screening trial, the assay was unable to discriminate between asymptomatic high-risk individuals with or without early stage lung cancer. On the contrary, in two independent cohorts of individuals with indeterminate pulmonary nodules, plasma samples from patients with lung cancer nodules presented higher levels of C4d than those from patients with benign nodules. Using a target population of patients with 8 to 30 mm nodules, the test identified likely benign lung nodules with 84% negative predictive value and 54% positive predictive value, at 89% specificity and 44% sensitivity. In conclusion, the specific determination of C4d may serve as an adjunct to current clinical practice in the diagnosis of indeterminate pulmonary nodules.
Author Daniel Ajona
Daniel Ajona,,
, Marcin Okrój (IFB / DMedB)
Marcin Okrój,,
- Department of Medical Biotechnology
, María J. Pajares
María J. Pajares,,
, Jackeline Agorreta
Jackeline Agorreta,,
, María D. Lozano
María D. Lozano,,
, Javier J. Zulueta
Javier J. Zulueta,,
, Carla Verri
Carla Verri,,
, Luca Roz
Luca Roz,,
, Gabriella Sozzi
Gabriella Sozzi,,
, Ugo Pastorino
Ugo Pastorino,,
et al.`
Journal seriesOncotarget, ISSN 1949-2553, (A 40 pkt)
Issue year2018
Publication size in sheets0.5
Keywords in Englishlung cancer, diagnosis, biomarker, complement C4d, indeterminate pulmonary nodules
ASJC Classification2730 Oncology
Languageen angielski
LicenseJournal (articles only); published final; Uznanie Autorstwa (CC-BY); with publication
Score (nominal)40
Score sourcejournalList
ScoreMinisterial score = 40.0, 06-02-2020, ArticleFromJournal
Publication indicators Scopus SNIP (Source Normalised Impact per Paper): 2018 = 0.904; WoS Impact Factor: 2016 = 5.168 (2) - 2016=5.312 (5)
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