The prognostic value of serum C-reactive protein-bound serum amyloid A in early-stage lung cancer.

The prognostic value of serum C-reactive protein-bound serum amyloid A in early-stage lung cancer.
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血清C反应蛋白结合血清淀粉样蛋白A在早期肺癌中的预后价值。

DOI:
10.1186/s40880-015-0039-1
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发表时间:
2015-08-10
影响因子:
--
通讯作者:
Zeng MS
Zeng MS
中科院分区:
医学2区
文献类型:
--
作者:
Zhang XY;Zhang G;Jiang Y;Liu D;Li MZ;Zhong Q;Zeng SQ;Liu WL;Zeng MS

文献摘要

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据报道,血清C反应蛋白(CRP)水平升高在肺癌患者中具有预后意义。本研究旨在进一步鉴定CRP结合组分作为肺癌的预后标志物,并验证其预后价值。通过差异蛋白质组学分析从肺癌患者或健康对照的血清样品中获得的CRP结合组分。CRP结合血清淀粉样蛋白A(CRP-SAA)通过免疫共沉淀(IP)进行评价。采用酶联免疫吸附试验(ELISA)检测两个独立肺癌队列(回顾性队列,242例患者;前瞻性队列,222例患者)和健康对照组(159例受试者)的血清样本,评价CRP-SAA的预后价值。通过蛋白质组学分析在来自肺癌患者的血清样品中特异性地鉴定CRP-SAA。通过来自肺癌患者的血清样品和细胞培养基中的co-IP证实CRP与SAA的结合。CRP SAA水平明显高于健康对照组(0.37 ± 0.58 vs.0.03 ± 0.04,P < 0.001)。CRP-SAA水平升高与肺癌的严重临床特征显著相关。回顾性队列(风险比[HR] = 2.181,95%置信区间[CI] = 1.641-2.897,P < 0.001)和前瞻性队列(HR = 2.744,95%CI = 1.810-4.161,P < 0.001)中,CRP-SAA升高与较低的生存率相关。多因素考克斯分析显示CRP-SAA是肺癌独立的预后指标。值得注意的是,在I-II期患者中,只有CRP-SAA,而不是总SAA或CRP,在两个队列中显示出与总生存期显著相关。单因素和多因素考克斯分析也表明,CRP-SAA可作为早期肺癌患者的独立预后指标。CRP-SAA可能是一个比总SAA或CRP更好的肺癌预后指标,特别是在早期患者中。
Elevated levels of serum C-reactive protein (CRP) have been reported to have prognostic significance in lung cancer patients. This study aimed to further identify CRP-bound components as prognostic markers for lung cancer and validate their prognostic value. CRP-bound components obtained from the serum samples from lung cancer patients or healthy controls were analyzed by differential proteomics analysis. CRP-bound serum amyloid A (CRP-SAA) was evaluated by co-immunoprecipitation (IP). Serum samples from two independent cohorts with lung cancer (retrospective cohort, 242 patients; prospective cohort, 222 patients) and healthy controls (159 subjects) were used to evaluate the prognostic value of CRP-SAA by enzyme-linked immunosorbent assay. CRP-SAA was identified specifically in serum samples from lung cancer patients by proteomic analysis. CRP binding to SAA was confirmed by co-IP in serum samples from lung cancer patients and cell culture media. The level of CRP-SAA was significantly higher in patients than in healthy controls (0.37 ± 0.58 vs. 0.03 ± 0.04, P < 0.001). Elevated CRP-SAA levels were significantly associated with severe clinical features of lung cancer. The elevation of CRP-SAA was associated with lower survival rates for both the retrospective (hazard ration [HR] = 2.181, 95% confidence interval [CI] = 1.641–2.897, P < 0.001) and the prospective cohorts (HR = 2.744, 95% CI = 1.810–4.161, P < 0.001). Multivariate Cox analysis showed that CRP-SAA was an independent prognostic marker for lung cancer. Remarkably, in stages I–II patients, only CRP-SAA, not total SAA or CRP, showed significant association with overall survival in two cohorts. Moreover, univariate and multivariate Cox analyses also showed that only CRP-SAA could be used as an independent prognostic marker for early-stage lung cancer patients. CRP-SAA could be a better prognostic marker for lung cancer than total SAA or CRP, especially in early-stage patients.