Serum biomarkers reflecting specific tumor tissue remodeling processes are valuable diagnostic tools for lung cancer
Serum biomarkers reflecting specific tumor tissue remodeling processes are valuable diagnostic tools for lung cancer
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DOI：
10.1002/cam4.303
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发表时间：
2014-10-01
期刊：
影响因子：
4
通讯作者：
Bay-Jensen, Anne-Christine
中科院分区：
文献类型：
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作者：
Willumsen, Nicholas;Bager, Cecilie L.;Bay-Jensen, Anne-Christine
细胞外基质（ECM）蛋白，如I型胶原蛋白和弹性蛋白，以及中间丝（IMF）蛋白，如波形蛋白，作为导致组织稳态破坏的恶性变化的一部分被修饰和失调。反映这种变化的非侵入性生物标志物可能对癌症有很大的潜力。在肺癌（n = 40）、胃肠癌（n = 25）、前列腺癌（n = 14）、恶性黑色素瘤（n = 7）、慢性阻塞性肺病（COPD）（n = 13）、和特发性肺纤维化（IPF）（n = 10），以及年龄匹配的对照组（n = 33）。计算受试者工作特征下的面积（AUROC），并根据特定的截止值生成诊断决策树。肺癌患者的C1 M和VICM显著高于健康对照组（AUROC = 0.98，P < 0.0001）和其他癌症（AUROC = 0.83，P < 0.0001）。当比较肺癌与COPD+IPF时，检测到一种趋势。ELM无差异。有趣的是，C1 M和VICM能够识别肺癌患者，阳性预测值为0.9，比值比为40（95%CI = 8.7-186，P < 0.0001）。特异性反映I型胶原蛋白和瓜氨酸化波形蛋白降解的生物标志物适用于肺癌患者。我们的数据表明，反映ECM和IMF蛋白失调的生物标志物在肺癌背景下非常适用。我们推测这些标记物可能有助于诊断和表征肺癌患者。
Extracellular matrix (ECM) proteins, such as collagen type I and elastin, and intermediate filament (IMF) proteins, such as vimentin are modified and dysregulated as part of the malignant changes leading to disruption of tissue homeostasis. Noninvasive biomarkers that reflect such changes may have a great potential for cancer. Levels of matrix metalloproteinase (MMP) generated fragments of type I collagen (C1M), of elastin (ELM), and of citrullinated vimentin (VICM) were measured in serum from patients with lung cancer (n = 40), gastrointestinal cancer (n = 25), prostate cancer (n = 14), malignant melanoma (n = 7), chronic obstructive pulmonary disease (COPD) (n = 13), and idiopathic pulmonary fibrosis (IPF) (n = 10), as well as in age-matched controls (n = 33). The area under the receiver operating characteristics (AUROC) was calculated and a diagnostic decision tree generated from specific cutoff values. C1M and VICM were significantly elevated in lung cancer patients as compared with healthy controls (AUROC = 0.98, P < 0.0001) and other cancers (AUROC = 0.83 P < 0.0001). A trend was detected when comparing lung cancer with COPD+IPF. No difference could be seen for ELM. Interestingly, C1M and VICM were able to identify patients with lung cancer with a positive predictive value of 0.9 and an odds ratio of 40 (95% CI = 8.7-186, P < 0.0001). Biomarkers specifically reflecting degradation of collagen type I and citrullinated vimentin are applicable for lung cancer patients. Our data indicate that biomarkers reflecting ECM and IMF protein dysregulation are highly applicable in the lung cancer setting. We speculate that these markers may aid in diagnosing and characterizing patients with lung cancer.