Department of Radiation Oncology, Shandong Academy of Medical Sciences, Jinan, People' Republic of China.
Neoplasma. 2013;60(1):11-8. doi: 10.4149/neo_2013_002.
To find potential serum biomakers that can predict clinical outcome upon treatment in non-small cell lung cancer (NSCLC) by analyzing differential proteins in serum with different sensitivity of chemoradiotherapy (CRT).
Sera were collected from 37 NSCLC patients before they were treated with concurrent cisplatin-based CRT. According to the outcome of CRT, the patients were divided into sensitive group and resistant one. The proteins in sera were separated by two-dimensional gel electrophoresis after the high abundance proteins were removed from sera. The significantly differentially expressed proteins between two groups were analyzed by liquid chromatography and tendem mass spectrometry (LC-MS/MS). Then, an additional 50 serum samples were used for ELISA analysis to validate the identified proteins that we got in the experiment.
Proteins in sera of each group were successfully separated on 2D gels. There were significant discrepancies in serum protein expression between NSCLC patients with different CRT sensitivity. Among eight differently expressed proteins, six proteins were successfully identified with five of which higher expressed and one lower expressed in resistant group. The increased Alpha-1-antitrypsin (α1-AT) level in resistant group comparing to sensitive one were validated by ELISA analysis (p<0.05).
Proteomic approach may serve as a useful method in detecting the potential biomarkers for predicting the outcome of treatment in NSCLC patients. NSCLC patients with high α1-AT level in serum before CRT may have a worse treatment outcome.
通过分析对放化疗（CRT）具有不同敏感性的血清中的差异蛋白，寻找能预测非小细胞肺癌（NSCLC）治疗后临床结果的潜在血清生物标志物。
收集 37 例 NSCLC 患者在接受顺铂为基础的 CRT 治疗前的血清。根据 CRT 的结果，将患者分为敏感组和耐药组。从血清中去除高丰度蛋白后，用二维凝胶电泳分离血清中的蛋白质。通过液相色谱和串联质谱（LC-MS/MS）分析两组间差异表达的蛋白质。然后，用 ELISA 分析另外 50 份血清样本，验证实验中得到的鉴定蛋白。
每个组的血清蛋白都成功地在 2D 凝胶上分离。不同 CRT 敏感性的 NSCLC 患者的血清蛋白表达存在显著差异。在 8 种差异表达的蛋白质中，有 6 种蛋白质被成功鉴定，其中 5 种在耐药组中表达升高，1 种表达降低。ELISA 分析验证了耐药组中 Alpha-1-抗胰蛋白酶（α1-AT）水平较敏感组升高（p<0.05）。
蛋白质组学方法可能是一种检测 NSCLC 患者治疗结果潜在生物标志物的有用方法。在 CRT 前血清中α1-AT 水平较高的 NSCLC 患者可能治疗效果较差。
