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中华临床实验室管理电子杂志 ›› 2015, Vol. 03 ›› Issue (03) : 171 -179. doi: 10.3877/cma.j.issn.2095-5820.2015.003.008

所属专题： 专题评论； 文献；

实验研究

中性粒细胞与淋巴细胞比率评估胃癌预后的Meta分析
卞炳贤, 周韵斓, 沈立松†   
  • 收稿日期:2015-07-31 出版日期:2015-08-28
  • 通信作者: 沈立松
  • 基金资助:
    国家自然科学基金资助项目(81372641，81401946)

Prognostic value of neutrophil-lymphocyte ratio in gastric cancer: a meta-analysis

Bingxian Bian, Yunlan Zhou, Lisong Shen†   

  • Received:2015-07-31 Published:2015-08-28
  • Corresponding author: Lisong Shen
  • About author:
    Corresponding author: SHEN Lisong, Email:
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引用本文：

卞炳贤, 周韵斓, 沈立松. 中性粒细胞与淋巴细胞比率评估胃癌预后的Meta分析[J]. 中华临床实验室管理电子杂志, 2015, 03(03): 171-179.

Bingxian Bian, Yunlan Zhou, Lisong Shen. Prognostic value of neutrophil-lymphocyte ratio in gastric cancer: a meta-analysis[J]. Chinese Journal of Clinical Laboratory Management(Electronic Edition), 2015, 03(03): 171-179.

目的

分析探讨中性粒细胞与淋巴细胞比率(neutrophil-lymphocyte ratio, NLR)对胃癌患者预后评估的价值。

方法

采用循证医学的meta分析研究。首先，从Embase、Medline和Web of Science数据库中检索关键词gastric cancer、stomach cancer、gastric carcinoma、stomach carcinoma、gastric neoplasm、stomach neoplasm、neutrophil和lymphocyte。然后，根据各纳入研究的总生存率(overall survival, OS)和无进展生存期(progression-free survival, PFS)/无疾病生存期(disease-free survival, DFS)合并生存危险比(hazard ratio, HR)的异质性，决定用固定或随机效应模型计算OS和PFS/DFS的合并HR。若合并HR>1，且其95%可信区间(confidence interval, CI)也>1, 则为NLR升高与胃癌患者OS或PFS/DFS的降低有显著联系。

结果

收集18篇文献共纳入5 065例胃癌患者进行meta分析。升高的NLR与OS降低存在显著关联(HR为1.79，95%CI 1.54~2.08)。亚组分析中，胃癌多种治疗方案组和化疗组NLR升高均与OS降低存在显著关联[HR分别为1.84, (95% CI 1.48~2.29)和1.69, (95% CI 1.41~2.03)]；而NLR≤3.2组和NLR>3.2组亦均与OS的降低存在显著关联[HR分别为1.80, (95% CI 1.46~2.23)和1.93, (95% CI 1.58~2.36)]。在胃癌患者OS的单因素meta回归分析中, 发表年份、种族、NLR临界值、治疗方案、患者数、进展期患者比例和男性比例都不是引起胃癌患者异质性来源的可能原因(P值分别为0.585、0.887、0.731、0.697、0.613、0.877、0.775)。

结论

胃癌患者中升高的NLR与OS降低存在显著的关联，NLR可作为评价胃癌患者预后的标志物。

关键词: 中性粒细胞与淋巴细胞比率, 胃癌, 预后, 标志物
Objective

The neutrophil-lymphocyte ratio (NLR) may indicate the balance of the inflammatory and immune systems, making NLR a useful index to evaluate tumor development. However, its prognostic value in patients with gastric cancer was still unclear. A meta-analysis was performed to characterize the prognostic effect of NLR.

Methods

An extensive literary search for relevant studies was conducted on Embase, Medline and Web of Science databases. The search strategy included the following keywords "gastric cancer", "stomach cancer", "gastric carcinoma", "stomach carcinoma", "gastric neoplasm", "stomach neoplasm", "neutrophil" and "lymphocyte" . Effect measure was hazard ratio (HR) for overall survival (OS) and progression-free survival(PFS) /disease-free survival (DFS). Then pooled HRs and 95% confidence intervals (CIs) were calculated using the random or fixed effect models by the heterogeneity of included studies. The pooled HR and 95% CI >1 indicated elevated NLR was associated with a significantly poorer OS.

Results

This meta-analysis has been based on 18 publications and comprises a total of 5 065 patients with gastric cancer. The pooled HR showed that elevated NLR was associated with a significantly poorer OS (HR 1.79, 95%CI 1.54-2.08). Subgroup analysis showed the prognostic effect of NLR was identical in multiple treatment methods subgroup and chemotherapy subgroup[HR 1.84, (95% CI 1.48-2.29) and 1.69, (95% CI 1.41-2.03), respectively]. The same effect was also seen in NLR≤3.2 subgroup and NLR>3.2 subgroup [HR 1.80, (95% CI 1.46-2.23) and 1.93, (95% CI 1.58-2.36), respectively]. At univariate meta-regression analysis in OS, the results indicated publication year, ethnicity, NLR cutoff value, treatment type, sample size, proportion of patients in advanced stage and proportion of male did not contribute to the cause of heterogeneity(P value of 0.585, 0.887, 0.731, 0.697, 0.613, 0.877, 0.775).

Conclusion

The overall findings of this study support the hypothesis that elevated NLR is associated with a significantly poorer OS and NLR could be a prognostic marker in gastric cancer.

Key words: Neutrophil-lymphocyte ratio, Gastric cancer, Prognosis, Biomarker
图1 文献检索及选择图
表1 纳入文献的基本特征
文献作者 年份 国家 患者例数 男性比例[例（%）] 分期进展期比例(%) 临界值 结局 获得HR方式
Hirashima等[11] 1998 日本 55 40(72.7) I (0.0) 2.0 OS 数据估算
Yamanaka等[18] 2007 日本 1 220 869(71.2) IV(100.0) 2.5 OS 文献获得
Ubukata等[19] 2010 日本 217 171(78.8) I～IV (36.9) 5.0 OS 文献获得
Shimada等[20] 2010 日本 1 028 709(69.0) I～IV (30.4) 4.0 OS 文献获得
Ubukata等[21] 2010 日本 157 106(67.5) I～IV (52.2) 5.0 OS 文献获得
Mohri等[22] 2010 日本 357 245(68.6) I～III (19.0) 2.2 OS 文献获得
Jung等[23] 2011 韩国 293 193(65.9) III～IV(100.0) 2.0 OS 文献获得
3.0 DFS
Aizawa等[24] 2011 日本 61 未提供 未提供 3.2 OS 文献获得
Wang等[25] 2012 中国 324 225(69.4) III(100.0) 5.0 OS, DFS 文献获得
Jeong等[26] 2012 韩国 104 69(66.3) IV(100.0) 5.0 OS、PFS 文献获得
Kunisaki等[13] 2012 日本 83 57(68.7) III～IV(100.0) 5.0 OS 文献获得
Dutta等[27] 2012 英国 120 78(65.0) I～III (30.8) 未提供 OS 文献获得
Lee等[28] 2013 韩国 174 114(65.5) 进展期(100.0) 3.0 OS 文献获得
Dirican等[29] 2013 土耳其 236 162(68.6) I～IV (89.0) 3.8 OS、PFS 文献获得
Jin等[30] 2013 中国 46 36(78.3) III～IV(100.0) 2.5 OS、PFS 文献获得
Lee等[31] 2013 韩国 220 149(67.7) I～IV (29.5) 2.2 OS 文献获得
Cho等[32] 2014 韩国 268 175(65.3) 进展期(100.0) 3.0 OS、PFS 文献获得
Aurello等[12] 2014 意大利 102 62(60.8) I～IV (52.0) 5.0 OS、DFS 文献获得
表2 胃癌患者病情主要结果
文献作者 结局 HR 95% CI NOS
Hirashima等[11] OS 6.22 2.09～18.49 6
Yamanaka等[18] OS 1.52 1.32～1.75 7
Ubukata等[19] OS 1.43 0.87～2.37 6
Shimada等[20] OS 1.85 1.24～2.75 7
Ubukata等[21] OS 5.78 0.95～35.17 7
Mohri等[22] OS 2.78 1.79～4.36 6
Jung等[23] OS 1.46 1.03～2.07 7
DFS 1.65 1.09～2.52
Aizawa等[24] OS 2.21 1.19～4.10 6
Wang等[25] OS 1.87 0.90～3.87 6
DFS 1.76 0.88～3.51
Jeong等[26] OS 1.65 1.03～2.64 7
PFS 1.88 1.25～2.82
Kunisaki等[13] OS 1.71 0.94～3.11 6
Dutta等[27] OS 1.19 0.76～1.87 6
Lee等[28] OS 2.24 2.09～3.63 7
Dirican等[29] OS 2.74 1.90～3.70 6
PFS 2.39 1.84～3.11
Jin等[30] OS 1.67 0.63～4.43 6
PFS 2.33 1.07～5.07
Lee等[31] OS 0.83 0.40～1.69 6
Cho等[32] OS 1.57 1.23～2.01 6
PFS 1.48 1.15～1.89
Aurello等[12] OS 1.51 0.69～3.28 6
DFS 0.95 0.35～2.56
图2 总体生存率的meta分析森林图
图3 亚洲国家亚组和白种人国家亚组OS的meta分析森林图
图4 多种治疗方案亚组和化疗亚组总体OS的meta分析森林图
图5 NLR≤3.2亚组和NLR>3.2亚组总体OS的meta分析森林图
图6 胃癌患者NLR与DFS/PFS的meta分析森林图
表3 胃癌患者OS单因素meta回归分析
变量 系数 标准误 P值
发表年份 0.09 0.17 0.585
种族 0.03 0.22 0.887
NLR临界值 0.06 0.17 0.731
治疗方案 -0.07 0.17 0.697
患者数 -0.09 0.17 0.613
进展期患者比例 0.02 0.14 0.877
男性比例 0.47 1.60 0.775
图7 胃癌患者总体OS的Begg’s漏斗图
图8 胃癌患者总体OS敏感性的Meta分析图
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