Ajona Daniel, Okrój Marcin, Pajares María J, Agorreta Jackeline, Lozano María D, Zulueta Javier J, Verri Carla, Roz Luca, Sozzi Gabriella, Pastorino Ugo, Massion Pierre P, Montuenga Luis M, Blom Anna M, Pio Ruben
Program in Solid Tumors, Center for Applied Medical Research (CIMA), CIBERONC, and Navarra's Health Research Institute (IDISNA), Pamplona, Spain.
Department of Biochemistry and Genetics, School of Sciences, University of Navarra, Pamplona, Spain.
Oncotarget. 2017 Dec 26;9(5):6346-6355. doi: 10.18632/oncotarget.23690. eCollection 2018 Jan 19.
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.
开发有助于识别高危个体或诊断不明确肺结节的分子标志物，可能会对肺癌临床管理产生重大影响。在本研究中，我们评估了一种新开发的特异性检测补体C4d的ELISA的诊断潜力。我们在来自肺癌患者和对照组的五个独立血浆和支气管肺泡灌洗样本队列中测量了该标志物。在病例对照研究中，血浆样本中诊断肺癌的ROC曲线下面积为0.82（95%CI = 0.72 - 0.92），支气管肺泡灌洗液中为0.80（95%CI = 0.69至0.90）。在MILD CT筛查试验的一组血浆样本中，该检测方法无法区分有无早期肺癌的无症状高危个体。相反，在两个独立的不明确肺结节个体队列中，有肺癌结节患者的血浆样本中C4d水平高于良性结节患者。使用8至30毫米结节患者的目标人群，该检测方法识别可能的良性肺结节的阴性预测值为84%，阳性预测值为54%，特异性为89%，敏感性为44%。总之，C4d的特异性测定可作为当前临床实践中诊断不明确肺结节的辅助手段。
