Cytokine profile determined by data-mining analysis set into clusters of non-small-cell lung cancer patients according to prognosis
Cytokine profile determined by data-mining analysis set into clusters of non-small-cell lung cancer patients according to prognosis
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DOI：
10.1093/annonc/mdu549
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发表时间：
2015-02-01
影响因子：
50.5
通讯作者：
Arrieta, O.
中科院分区：
文献类型：
--
作者：
Barrera, L.;Montes-Servin, E.;Arrieta, O.
背景：免疫调节细胞因子可能在肿瘤生长和转移中起重要作用。它们的影响是通过复杂的调控网络介导的。人类细胞因子谱可以定义患者亚组并代表新的潜在生物标志物。本研究的目的是将通过数据挖掘获得的细胞因子与晚期非小细胞肺癌（NSCLC）患者的临床特征相关联。患者和方法：我们进行了一项前瞻性研究，110例NSCLC患者化疗前和25例对照组的14种免疫调节细胞因子的血浆水平，ELISA和流式细胞仪珠阵列检测。结果：NSCLC患者IL-6、IL-8、IL-12 p70、IL-17 a和IFN-γ水平高于对照组，IL-33和IL-29水平低于对照组。促炎细胞因子IL-1b、IL-6和IL-8与较低的血红蛋白水平、较差的功能状态（东部肿瘤协作组，ECOG）、疲劳和食欲减退相关。抗炎细胞因子IL-4、IL-10和IL-33与厌食症和较低的体重指数相关。根据数据挖掘分析，我们确定了三组具有不同总生存期的患者（OS;分别为25.4、16.8和5.09个月，P = 0.0012）。多因素分析显示，ECOG体力状态和数据挖掘聚类与OS显著相关（RR 3.59，95%CI 1.9-6.7，P < 0.001和2.2，95%CI 1.2-3.8，P = 0.005）。结论：本研究结果为复杂细胞因子网络可用于鉴别晚期NSCLC患者的不同疾病亚群提供了证据。这些细胞因子可能代表潜在的生物标志物，特别是在癌症研究的免疫治疗时代。
Background: Immunoregulatory cytokines may play a fundamental role in tumor growth and metastases. Their effects are mediated through complex regulatory networks. Human cytokine profiles could define patient subgroups and represent new potential biomarkers. The aim of this study was to associate a cytokine profile obtained through data mining with the clinical characteristics of patients with advanced non-small-cell lung cancer (NSCLC).Patients and methods: We conducted a prospective study of the plasma levels of 14 immunoregulatory cytokines by ELISA and a cytometric bead array assay in 110 NSCLC patients before chemotherapy and 25 control subjects. Cytokine levels and data-mining profiles were associated with clinical, quality of life and pathological outcomes.Results: NSCLC patients had higher levels of interleukin (IL)-6, IL-8, IL-12p70, IL-17a and interferon (IFN)-gamma, and lower levels of IL-33 and IL-29 compared with controls. The pro-inflammatory cytokines IL-1b, IL-6 and IL-8 were associated with lower hemoglobin levels, worse functional performance status (Eastern Cooperative Oncology Group, ECOG), fatigue and hyporexia. The anti-inflammatory cytokines IL-4, IL-10 and IL-33 were associated with anorexia and lower body mass index. We identified three clusters of patients according to data-mining analysis with different overall survival (OS; 25.4, 16.8 and 5.09 months, respectively, P = 0.0012). Multivariate analysis showed that ECOG performance status and data-mining clusters were significantly associated with OS (RR 3.59, [95% CI 1.9-6.7], P < 0.001 and 2.2, [1.2-3.8], P = 0.005).Conclusion: Our results provide evidence that complex cytokine networks may be used to identify patient subgroups with different prognoses in advanced NSCLC. These cytokines may represent potential biomarkers, particularly in the immunotherapy era in cancer research.