Investigation of Complement Activation Product C4d as a Diagnostic and Prognostic Biomarker for Lung Cancer
Investigation of Complement Activation Product C4d as a Diagnostic and Prognostic Biomarker for Lung Cancer
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DOI：
10.1093/jnci/djt205
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发表时间：
2013-09-01
影响因子：
10.3
通讯作者：
Pio, Ruben
中科院分区：
文献类型：
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作者：
Ajona, Daniel;Pajares, Maria J.;Pio, Ruben
背景肺癌的诊断生物标记物在医学上是有必要的。我们评估了补体激活片段的诊断性能。方法我们评估了4个支气管上皮细胞系和7个肺癌细胞系的补体激活。检测了90例原发性肺癌患者、50例肺癌患者和22例非恶性呼吸系统疾病患者的支气管肺泡灌洗上清液、50例晚期肺癌患者和84例早期肺癌患者、133例炎症性肺部疾病患者和190例无症状肺癌患者的血浆中补体激活的降解产物C4D。用Mann-Whitney U检验计算双侧P值。结果肺癌细胞激活了由C1q结合介导的经典补体途径，而C1q结合途径被磷酸单酯抑制。肿瘤中C4D沉积高的患者生存率降低(危险比[HR]=3.06；95%可信区间[CI]=1.18-7.91)。肺癌患者支气管肺泡灌洗液中C4D水平明显高于非恶性呼吸系统疾病患者(0.61±0.87 vs 0.16+/-0.11µg/mL，P<0.01)。晚期肺癌患者和早期肺癌患者血浆C4D水平均高于对照组(分别为4.13±2.02vs1.86+/-0.95mU/mL，P&0.001；3.18+/-3.20vs1.13+/-0.69mU/mLP<；0.001vs1.13+/-0.69mU/mLP<；晚期(HR=1.59；95%CI=0.97~2.60)和早期(HR=5.57；95%CI=1.60~19.39)患者的生存期较短。肺癌患者手术切除后血浆C4D水平降低(P<；.001)，并与无症状肺癌患者(n=32)和非肺癌患者(n=158)患肺癌的危险性增加有关(优势比=4.38；95%CI=1.61~11.93)。结论补体片段C4D可作为肺癌早期诊断和预后判断的生物标志物。
Background There is a medical need for diagnostic biomarkers in lung cancer. We evaluated the diagnostic performance of complement activation fragments.Methods We assessed complement activation in four bronchial epithelial and seven lung cancer cell lines. C4d, a degradation product of complement activation, was determined in 90 primary lung tumors; bronchoalveolar lavage supernatants from patients with lung cancer (n = 50) and nonmalignant respiratory diseases (n = 22); and plasma samples from advanced (n = 50) and early lung cancer patients (n = 84) subjects with inflammatory lung diseases (n = 133), and asymptomatic individuals enrolled in a lung cancer computed tomography screening program (n = 190). Two-sided P values were calculated by Mann-Whitney U test.Results Lung cancer cells activated the classical complement pathway mediated by C1q binding that was inhibited by phosphomonoesters. Survival was decreased in patients with high C4d deposition in tumors (hazard ratio [HR] = 3.06; 95% confidence interval [CI] = 1.18 to 7.91). C4d levels were increased in bronchoalveolar lavage fluid from lung cancer patients compared with patients with nonmalignant respiratory diseases (0.61 +/- 0.87 vs 0.16 +/- 0.11 mu g/mL; P < .001). C4d levels in plasma samples from lung cancer patients at both advanced and early stages were also increased compared with control subjects (4.13 +/- 2.02 vs 1.86 +/- 0.95 mu g/mL, P < 0.001; 3.18 +/- 3.20 vs 1.13 +/- 0.69 mu g/mL, P < .001, respectively). C4d plasma levels were associated with shorter survival in patients at advanced (HR = 1.59; 95% CI = 0.97 to 2.60) and early stages (HR = 5.57; 95% CI = 1.60 to 19.39). Plasma C4d levels were reduced after surgical removal of lung tumors (P < .001) and were associated with increased lung cancer risk in asymptomatic individuals with (n = 32) or without lung cancer (n = 158) (odds ratio = 4.38; 95% CI = 1.61 to 11.93).Conclusions Complement fragment C4d may serve as a biomarker for early diagnosis and prognosis of lung cancer.