Translating biomarkers into clinical practice: prognostic implications of cyclophilin A and macrophage migratory inhibitory factor identified from protein expression profiles in non-small cell lung cancer

Translating biomarkers into clinical practice: prognostic implications of cyclophilin A and macrophage migratory inhibitory factor identified from protein expression profiles in non-small cell lung cancer
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DOI:
10.1016/j.lungcan.2004.05.013
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发表时间:
2004-12-01
期刊:
影响因子:
5.3
通讯作者:
Patz, EF
Patz, EF
中科院分区:
医学2区
文献类型:
--
作者:
Howard, BA;Zheng, Z;Patz, EF

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生物标志物有可能显著改变诊断策略并影响治疗管理。我们开发了一个MALDI-TOF蛋白表达盈利平台,用于生物标志物发现和原理验证研究,确定了两种蛋白质,亲环素A(CyPA)和巨噬细胞迁移抑制因子(MIF),在非小细胞肺癌(NSCLC)中过表达。目前的研究重点是评估CyPA和MIF作为肺癌新诊断患者预后标志物的潜力,以快速转化为临床实践。通过组织微阵列免疫组织化学(TMA-IHC)检查了234例反映广泛组织学和分期的原发性NSCLC标本的CyPA和MIF反应性。通过Kaplan-Meier曲线、对数秩检验和考克斯模型统计,将肿瘤细胞反应性百分比、染色强度和复合染色评分与患者总生存期进行比较。虽然这两种蛋白质在大多数NSCLC肿瘤中过表达,但CypA和MIF均未显示与结局相关。这种试点项目方法可以加快新发现的生物标志物整合到临床实践中,目的是改善患者分层到适当的治疗方案。虽然本研究中考虑的两种蛋白质在绝大多数NSCLC中过表达,但未发现它们具有预后意义。(C)2004爱思唯尔爱尔兰有限公司保留所有权利。
Biomarkers have the potential to significantly change diagnostic strategies and influence therapeutic management. We developed a MALDI-TOF protein expression profiting platform for biomarker discovery and a proof-of-principle study identified two proteins, cyclophilin A (CyPA) and macrophage migration inhibitory factor (MIF), that were overexpressed in non-small cell Lung cancer (NSCLC). The current study focused on evaluating the potential of CyPA and MIF as prognostic markers in patients with a new diagnosis of lung cancer for rapid translation into clinical practice. Two hundred and thirty-four primary NSCLC specimens reflecting a broad range of histologies and stages were examined for CyPA and MIF reactivity by tissue microarray immunohistochemistry (TMA-IHC). The percent tumor cell reactivity, staining intensity and a composite staining score were compared with overall patient survival by Kaplan-Meier curves, log rank test and Cox model statistics. Although both proteins were overexpressed in most NSCLC tumors, neither CypA nor MIF showed a correlation with outcome. This pilot project approach can expedite integration of newly discovered biomarkers into clinical practice, with the goal of improving stratification of patients into appropriate treatment regimens. While both proteins considered in this study were overexpressed in the vast majority of NSCLCs, they were not found to be of prognostic significance. (C) 2004 Elsevier Ireland Ltd. All rights reserved.