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首页> 外文期刊>EBioMedicine >Discovery and Validation of Predictive Biomarkers of Survival for Non-small Cell Lung Cancer Patients Undergoing Radical Radiotherapy: Two Proteins With Predictive Value
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Discovery and Validation of Predictive Biomarkers of Survival for Non-small Cell Lung Cancer Patients Undergoing Radical Radiotherapy: Two Proteins With Predictive Value

机译：发现和验证非小细胞肺癌接受放射治疗的患者生存的预测生物标志物：两种具有预测价值的蛋白质

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摘要

Lung cancer is the most frequent cause of cancer-related death world-wide. Radiotherapy alone or in conjunction with chemotherapy is the standard treatment for locally advanced non-small cell lung cancer (NSCLC). Currently there is no predictive marker with clinical utility to guide treatment decisions in NSCLC patients undergoing radiotherapy. Identification of such markers would allow treatment options to be considered for more effective therapy. To enable the identification of appropriate protein biomarkers, plasma samples were collected from patients with non-small cell lung cancer before and during radiotherapy for longitudinal comparison following a protocol that carries sufficient power for effective discovery proteomics. Plasma samples from patients pre- and during radiotherapy who had survived >18mo were compared to the same time points from patients who survived <14mo using an 8 channel isobaric tagging tandem mass spectrometry discovery proteomics platform. Over 650 proteins were detected and relatively quantified. Proteins which showed a change during radiotherapy were selected for validation using an orthogonal antibody-based approach. Two of these proteins were verified in a separate patient cohort: values of CRP and LRG1 combined gave a highly significant indication of extended survival post one week of radiotherapy treatment.
机译：肺癌是全世界与癌症相关的死亡的最常见原因。单独放疗或联合放疗是局部晚期非小细胞肺癌（NSCLC）的标准治疗方法。当前，尚无具有临床实用性的预测标记物可指导接受放疗的NSCLC患者的治疗决策。鉴定这些标志物将允许考虑治疗方案以进行更有效的治疗。为了能够鉴定适当的蛋白质生物标志物，在放疗之前和期间从非小细胞肺癌患者中收集血浆样品，按照具有足够功效进行有效蛋白质组学研究的方案进行纵向比较。使用8通道等压标记串联质谱发现蛋白质组学平台，比较了放疗前和放疗中存活时间> 18mo的患者血浆样品与存活<14mo的患者的相同时间点。检测并相对定量了650多种蛋白质。使用基于正交抗体的方法选择放射治疗过程中显示出变化的蛋白质进行验证。在一个单独的患者队列中验证了其中两种蛋白质：CRP和LRG1的组合值在放疗一周后显示了延长的生存期。

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