Cytokine profile and prognostic significance of high neutrophil-lymphocyte ratio in colorectal cancer.
Cytokine profile and prognostic significance of high neutrophil-lymphocyte ratio in colorectal cancer.
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结直肠癌中高中性粒细胞与淋巴细胞比值的细胞因子谱及其预后意义
DOI：
10.1038/bjc.2015.61
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发表时间：
2015-03-17
影响因子：
8.8
通讯作者：
Kopetz, S.
中科院分区：
文献类型：
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作者：
Chen, Z-Y;Raghav, K.;Lieu, C. H.;Jiang, Z-Q;Eng, C.;Vauthey, J-N;Chang, G. J.;Qiao, W.;Morris, J.;Hong, D.;Hoff, P.;Tran, H.;Menter, D. G.;Heymach, J.;Overman, M.;Kopetz, S.
关键词：
高循环嗜中性粒细胞-淋巴细胞比率（NLR）似乎是转移性结直肠癌（mCRC）的预后。我们研究了NLR与循环细胞因子和分子改变的关系。我们对多个队列的CRC患者进行了回顾性分析（未治疗的转移性（n= 166），难治性转移性（n=161），肝切除术（n=198），2/3期（n=274）和分子筛选（n=342））。高NLR（外周血中嗜中性粒细胞与淋巴细胞绝对计数的比率）定义为NLR>5。使用多重珠测定法评价血浆细胞因子。采用Kaplan-Meier估计、非参数相关分析和分层聚类分析。高NLR与mCRC的不良预后相关（风险比（HR）1.73; 95%置信区间（CI）：1.03-2.89; P=0.039），与已知的预后因素和分子改变（KRAS/NRAS/BRAF/PIK 3CA/CIMP）无关。在探索性队列（n=39）和验证队列（n=166）中，高NLR与白细胞介素6（IL-6）、IL-8、IL-2 R α、肝细胞生长因子、巨噬细胞集落刺激因子和血管表皮生长因子的表达增加相关。另外14种细胞因子与验证队列中的高NLR相关。所有20种细胞因子分为三大类：炎性细胞因子、血管生成细胞因子和表皮生长因子配体。在mCRC中，基于NLR-细胞因子评分的复合分层提供了超过NLR的增强的预后信息（HR 2.09; 95% CI：1.59-2.76; P<0.001）。高NLR是CRC中独立的不良预后标志物，与致癌过程中关键生物学过程相关的独特细胞因子谱相关。复合NLR-细胞因子分层增强了mCRC的预后价值。
High circulating neutrophil-lymphocyte ratio (NLR) appears to be prognostic in metastatic colorectal cancer (mCRC). We investigated the relationship of NLR with circulating cytokines and molecular alterations. We performed retrospective analyses on multiple cohorts of CRC patients (metastatic untreated (n=166), refractory metastatic (n=161), hepatectomy (n=198), stage 2/3 (n=274), and molecularly screened (n=342)). High NLR (ratio of absolute neutrophil-to-lymphocyte counts in peripheral blood) was defined as NLR>5. Plasma cytokines were evaluated using multiplex-bead assays. Kaplan–Meier estimates, non-parametric correlation analysis, and hierarchical cluster analyses were used. High NLR was associated with poor prognosis in mCRC (hazard ratio (HR) 1.73; 95% confidence interval (CI):1.03–2.89; P=0.039) independent of known prognostic factors and molecular alterations (KRAS/NRAS/BRAF/PIK3CA/CIMP). High NLR correlated with increased expression of interleukin 6 (IL-6), IL-8, IL-2Rα, hepatocyte growth factor, macrophage-colony stimulating factor, and vascular epidermal growth factor in exploratory (n=39) and validation (n=166) cohorts. Fourteen additional cytokines correlated with high NLR in the validation cohort. All 20 cytokines fell into three major clusters: inflammatory cytokines, angiogenic cytokines, and epidermal growth factor ligands. In mCRC, composite stratification based on NLR-cytokine score provided enhanced prognostic information (HR 2.09; 95% CI: 1.59–2.76; P<0.001) over and above NLR. High NLR is an independent poor prognostic marker in CRC and correlates with a distinct cytokine profile related to key biological processes involved in carcinogenesis. A composite NLR-cytokine stratification has enhanced prognostic value in mCRC.
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影响因子：
3.8
作者：
Bandapalli, Obul R.;Ehrmann, Franziska;Brand, Karsten
通讯作者：
Brand, Karsten
影响因子：
8.8
作者：
Guthrie GJ;Roxburgh CS;Richards CH;Horgan PG;McMillan DC
通讯作者：
McMillan DC
DOI：
10.1158/1078-0432.ccr-13-0926
发表时间：
2013-12-15
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Nixon AB;Pang H;Starr MD;Friedman PN;Bertagnolli MM;Kindler HL;Goldberg RM;Venook AP;Hurwitz HI;Alliance for Clinical Trials In Oncology
通讯作者：
Alliance for Clinical Trials In Oncology
影响因子：
3.5
作者：
Inoue, Yasuhiro;Iwata, Takashi;Kusunoki, Masato
通讯作者：
Kusunoki, Masato
影响因子：
8.4
作者：
LISSONI, P;BARNI, S;TANCINI, G
通讯作者：
TANCINI, G