Division of Thoracic Surgery, Otto Wagner Hospital, Vienna, Austria.
Eur J Cardiothorac Surg. 2013 May;43(5):940-5. doi: 10.1093/ejcts/ezs521. Epub 2012 Oct 7.
Integrin-linked kinase (ILK) is an intracellular protein implicated in chronic inflammation and neoplastic transformation. In a recently accomplished pilot study, we showed that ILK can be detected in the serum of patients with benign and malignant chest diseases, including malignant pleural mesothelioma (MPM). Interestingly, average serum ILK concentrations were 10 times higher in MPM patients when compared with the rest of the study population, and a diagnostic test solely based on serum ILK concentration could discriminate between MPM and non-MPM with considerable accuracy. This study aimed to investigate whether serum ILK concentration could also be used to discriminate between MPM and asbestos exposure only.
Using a self-developed sandwich enzyme-linked immunosorbent assay, we measured serum ILK concentrations in 101 MPM patients, and 96 asbestos-exposed, but healthy insulation workers. Seventy-three MPM patients had an epitheloid subtype (72.3%), and 42 had a Stage I or II disease (41.6%).
When compared with asbestos-exposed individuals, MPM patients of all clinical stages had significantly higher (mean ± standard deviation, median) serum ILK concentrations (10.7 ± 13.6, median 7 ng/ml vs 3.1 ± 4.6, median 1.4 ng/ml; P < 0.001). Among MPM patients, the serum ILK concentration was significantly higher at advanced disease stages III + IV than at early stages I + II (13.7 ± 15.9, median 8.5 ng/ml vs 6.7 ± 7.8, median 3.5 ng/ml; P = 0.02). Using serum ILK to discriminate between MPM patients and asbestos-exposed individuals yielded an area under the curve of 0.69 (95% confidence interval 0.63-0.76). The corresponding sensitivity and specificity for a cut-off of 4.49 ng/ml ILK are 61.4 and 80.2%, respectively.
These data show significant differences between MPM patients and asbestos-exposed but healthy individuals concerning their serum ILK concentration. Furthermore, since ILK levels are increased in advanced MPM stages in comparison with early MPM stages, we suggest evaluating its potential use as a marker of disease progression in MPM.
整合素连接激酶(ILK)是一种与慢性炎症和肿瘤转化有关的细胞内蛋白。在最近完成的一项试点研究中,我们发现 ILK 可以在患有良性和恶性胸部疾病的患者的血清中检测到,包括恶性胸膜间皮瘤(MPM)。有趣的是,与研究人群中的其他患者相比,MPM 患者的平均血清 ILK 浓度高 10 倍,并且仅基于血清 ILK 浓度的诊断测试可以以相当高的准确性区分 MPM 和非 MPM。本研究旨在探讨血清 ILK 浓度是否也可用于区分 MPM 和仅石棉暴露。
使用自行开发的夹心酶联免疫吸附试验,我们测量了 101 名 MPM 患者和 96 名石棉暴露但健康的绝缘工人的血清 ILK 浓度。73 名 MPM 患者为上皮样亚型(72.3%),42 名患者为 I 期或 II 期疾病(41.6%)。
与石棉暴露个体相比,所有临床阶段的 MPM 患者的血清 ILK 浓度(平均值±标准差,中位数)均显着升高(10.7 ± 13.6,中位数 7ng/ml 与 3.1 ± 4.6,中位数 1.4ng/ml;P <0.001)。在 MPM 患者中,晚期疾病阶段 III + IV 的血清 ILK 浓度显着高于早期疾病阶段 I + II(13.7 ± 15.9,中位数 8.5ng/ml 与 6.7 ± 7.8,中位数 3.5ng/ml;P = 0.02)。使用血清 ILK 区分 MPM 患者和石棉暴露个体的曲线下面积为 0.69(95%置信区间 0.63-0.76)。ILK 为 4.49ng/ml 时的灵敏度和特异性分别为 61.4%和 80.2%。
这些数据显示 MPM 患者与石棉暴露但健康个体的血清 ILK 浓度存在显着差异。此外,由于与早期 MPM 阶段相比,晚期 MPM 阶段的 ILK 水平升高,我们建议评估其作为 MPM 疾病进展标志物的潜在用途。