Stoller Biomarker Discovery Centre, Manchester Academic Health Science Centre, The University of Manchester, Wolfson Molecular Imaging Centre, Manchester M20 3LJ, UK.
Stoller Biomarker Discovery Centre, Manchester Academic Health Science Centre, The University of Manchester, Wolfson Molecular Imaging Centre, Manchester M20 3LJ, UK ; Clinical and Experimental Pharmacology Group, Cancer Research UK Manchester Institute, Manchester Academic Health Science Centre, Christie Hospital, University of Manchester, Manchester M20 4BX, UK.
EBioMedicine. 2015 Jun 19;2(8):841-50. doi: 10.1016/j.ebiom.2015.06.013. eCollection 2015 Aug.
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 > 18 mo were compared to the same time points from patients who survived < 14 mo 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.
肺癌是全球癌症相关死亡的最常见原因。单独放疗或联合化疗是局部晚期非小细胞肺癌（NSCLC）的标准治疗方法。目前，尚无具有临床实用性的预测标志物来指导接受放疗的 NSCLC 患者的治疗决策。鉴定此类标志物将允许考虑更有效的治疗选择。为了能够鉴定适当的蛋白质生物标志物，按照具有有效发现蛋白质组学能力的方案，在对非小细胞肺癌患者进行放射治疗之前和期间收集血浆样本，以便进行纵向比较。使用 8 通道同位素质谱标记串联质谱发现蛋白质组学平台，将放疗前和放疗期间存活时间> 18 个月的患者与存活时间< 14 个月的患者的相同时间点的血浆样本进行比较。检测到并相对定量了超过 650 种蛋白质。选择在放疗过程中发生变化的蛋白质，使用正交抗体方法进行验证。其中两种蛋白质在单独的患者队列中得到了验证：CRP 和 LRG1 的值结合起来，对放疗治疗一周后延长的生存时间具有高度显著的指示意义。
