Investigation of Complement Activation Product C4d as a Diagnostic and Prognostic Biomarker for Lung Cancer

被引：157

作者：

Ajona, Daniel ^{[1
]}

Pajares, Maria J. ^{[1
,2
]}

Corrales, Leticia ^{[1
]}

Perez-Gracia, Jose L. ^{[4
]}

Agorreta, Jackeline ^{[1
,2
]}

Lozano, Maria D. ^{[5
]}

Torre, Wenceslao ^{[6
]}

Massion, Pierre P. ^{[8
]}

de-Torres, Juan P. ^{[7
]}

Jantus-Lewintre, Eloisa ^{[11
]}

Camps, Carlos ^{[9
,10
]}

Zulueta, Javier J. ^{[7
]}

Montuenga, Luis M. ^{[1
,2
]}

Pio, Ruben ^{[1
,3
]}

机构：

[1] Ctr Appl Med Res, Div Oncol, Pamplona, Spain

[2] Univ Navarra, Dept Histol & Pathol, Sch Med, E-31080 Pamplona, Spain

[3] Univ Navarra, Dept Biochem & Genet, Sch Med, E-31080 Pamplona, Spain

[4] Univ Navarra Clin, Dept Oncol, Pamplona, Spain

[5] Univ Navarra Clin, Dept Pathol, Pamplona, Spain

[6] Univ Navarra Clin, Dept Thorac Surg, Pamplona, Spain

[7] Univ Navarra Clin, Dept Pulm Med, Pamplona, Spain

[8] Vanderbilt Univ, Med Ctr, Thorac Program, Vanderbilt Ingram Canc Ctr, Nashville, TN USA

[9] Univ Valencia, Dept Med, Valencia, Spain

[10] Hosp Gen Univ Valencia, Dept Med Oncol, Valencia, Spain

[11] Fdn Invest Hosp Gen Univ Valencia, Mol Oncol Lab, Valencia, Spain

来源：

JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE | 2013年 / 105卷 / 18期

关键词：

FACTOR-H; IMMUNE-RESPONSE; CELLS; INHIBITION; EXPRESSION; PATHWAY; SYSTEM; CONFER; C1Q;

D O I：

10.1093/jnci/djt205

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 [肿瘤学];

摘要：

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.

引用

页码：1385 / 1393

页数：9

共 30 条

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