Guadagni F, Ferroni P, Basili S, Facciolo F, Carlini S, Crecco M, Martini F, Spila A, D'Alessandro R, Aloe S, Cerasoli V, Del Monte G, Mariotti S, Mineo T C, Roselli M
Laboratory of Clinical Pathology, Regina Elena Cancer Institute, Via E. Chianesi 53, Rome 00144, Italy.
Lung Cancer. 2004 Jun;44(3):303-10. doi: 10.1016/j.lungcan.2003.11.009.
The present study was designed to investigate whether a correlation exists between IL-6, TNF-alpha and coagulation (Thrombin-antithrombin, TATc) or fibrinolysis (D-dimer) activation in non-small cell lung cancer (NSCLC) patients. One hundred thirty patients with NSCLC (n=65, 53 males, mean age 65 +/- 8, adenocarcinoma n=32, squamous cancer n=33) or chronic obstructive pulmonary disease (COPD) (n=65, 51 males, mean age 67 +/- 9) were studied. As control group 65 healthy donors (51 males, mean age 61 +/- 14) were also evaluated. The results obtained showed that median D-dimer levels were higher in NSCLC patients (3.0 microg/ml) compared either to COPD patients (1.1 microg/ml, P<0.05) or controls (0.3 microg/ml, P<0.0001). Positive TNF-alpha levels (>10 pg/ml) were found in 26% of NSCLC compared to 3% of COPD (P<0.002) and 5% of controls (P<0.0005). On the other hand, positive (>8.5 pg/ml) IL-6 levels were found in 53% of NSCLC and 21% of COPD patients, compared to 5% of control subjects (P<0.001). Median TATc levels were elevated in either NSCLC (6.9 microg/l) or COPD (5.7 microg/l) patients compared to controls (1.8 microg/l, P<0.0001). Elevated D-dimer levels were significantly associated to positive TNF-alpha levels in patients without distant metastasis (F=4.3, P<0.05). Moreover, TNF-alpha levels (P<0.01) were independently related to the presence of positive D-dimer levels in patients with non-metastatic NSCLC. These results suggest that increased levels of TNF-alpha might be responsible for an activation of fibrinolysis in patients with NSCLC.
本研究旨在调查非小细胞肺癌(NSCLC)患者白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)与凝血(凝血酶-抗凝血酶复合物,TATc)或纤维蛋白溶解(D-二聚体)激活之间是否存在相关性。对130例NSCLC患者(n = 65,男性53例,平均年龄65±8岁,腺癌32例,鳞癌33例)或慢性阻塞性肺疾病(COPD)患者(n = 65,男性51例,平均年龄67±9岁)进行了研究。另外还评估了65名健康供者(男性51例,平均年龄61±14岁)作为对照组。结果显示,NSCLC患者的D-二聚体水平中位数(3.0微克/毫升)高于COPD患者(1.1微克/毫升,P<0.05)或对照组(0.3微克/毫升,P<0.0001)。26%的NSCLC患者TNF-α水平呈阳性(>10皮克/毫升),而COPD患者为3%(P<0.002),对照组为5%(P<0.0005)。另一方面,53%的NSCLC患者和21%的COPD患者IL-6水平呈阳性(>8.5皮克/毫升),而对照组为5%(P<0.001)。与对照组(1.8微克/升,P<0.0001)相比,NSCLC患者(6.9微克/升)或COPD患者(5.7微克/升)的TATc水平中位数均升高。在无远处转移的患者中,D-二聚体水平升高与TNF-α水平呈阳性显著相关(F = 4.3,P<0.05)。此外,在非转移性NSCLC患者中,TNF-α水平(P<0.01)与D-二聚体水平呈阳性独立相关。这些结果表明,TNF-α水平升高可能是NSCLC患者纤维蛋白溶解激活的原因。