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.
Highlights
IntroductionThe overall five-year survival rate for lung cancer is approximately 15–20%, and less than 5% in metastatic cases [2]
Lung cancer is the leading cause of cancer-related death worldwide [1]
In a previous study we found that the levels of C4d-containing complement degradation fragments were increased in bronchoalveolar lavage (BAL) samples from lung cancer patients when compared to samples from patients with nonmalignant lung diseases [13]
Summary
The overall five-year survival rate for lung cancer is approximately 15–20%, and less than 5% in metastatic cases [2]. Lung cancer diagnosis involves the combination of radiological and histological analyses of lesions. Flexible bronchoscopy represents a relatively noninvasive initial diagnostic test in individuals with suspected disease, and is the primary diagnostic tool in patients with centrally located lung cancer. Bronchoscopic techniques for the diagnosis of lung cancer include cytological examination of specimens from bronchial biopsy, bronchial brush, bronchial wash, and bronchoalveolar lavage (BAL) [3, 4]. Specificity of cytology of bronchoscopic material is 100%; sensitivity remains low, especially in more peripheral lesions, for which more invasive diagnostic procedures are routinely needed [5]. There is a clinical demand of adjunct markers that may improve the sensitivity of lung cancer diagnostic procedures
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