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Review
. 2014 Jun 6;9(6):e98259.
doi: 10.1371/journal.pone.0098259. eCollection 2014.

Tumor-associated neutrophils as a new prognostic factor in cancer: a systematic review and meta-analysis

Meixiao Shen  1 , Pingping Hu  1 , Frede Donskov  2 , Guanghui Wang  3 , Qi Liu  1 , Jiajun Du  4
Affiliations
Review

Tumor-associated neutrophils as a new prognostic factor in cancer: a systematic review and meta-analysis

Meixiao Shen et al. PLoS One. .

Abstract

Purpose: Tumor-associated neutrophils (TAN) have been reported in a variety of malignancies. We conducted an up-to-date meta-analysis to evaluate the prognostic role of TAN in cancer.

Method: Pubmed, Embase and web of science databases were searched for studies published up to April 2013. Pooled hazard ratios (HRs) and their corresponding 95% confidence intervals (CIs) were calculated. The impact of neutrophils localization and primary antibody were also assessed.

Results: A total of 3946 patients with various solid tumors from 20 studies were included. High density of intratumoral neutrophils were independently associated with unfavorable survival; the pooled HRs were 1.68 (95%CI: 1.36-2.07, I2 = 55.8%, p<0.001) for recurrence-free survival (RFS)/disease-free survival (DFS), 3.36 (95%CI: 2.08-5.42, I2 = 0%, p<0.001) for cancer-specific survival (CSS) and 1.66 (95%CI: 1.37-2.01, I2 = 70.5%, p<0.001) for overall survival (OS). Peritumoral and stromal neutrophils were not statistically significantly associated with survival. When grouped by primary antibody, the pooled HRs were 1.80 (95%CI: 1.47-2.22, I2 = 67.7%, p<0.001) for CD66b, and 1.44 (95%CI: 0.90-2.30, I2 = 45.9%, p = 0.125) for CD15, suggesting that CD66b positive TAN might have a better prognostic value than CD15.

Conclusion: High levels of intratumoral neutrophils are associated with unfavorable recurrence-free, cancer-specific and overall survival.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1. Follow diagram of the meta-analysis.
Figure 2
Figure 2. Forrest plots evaluating maximally adjusted association between TAN and clinical outcomes in all cancers.
(A) Forrest plot to assess the overall effect of TAN on OS in all cancer patients. (B) Forrest plot to assess the overall effect of TAN on RFS/DFS in all cancer patients.
Figure 3
Figure 3. Forrest plots evaluating maximally adjusted association between intratumoral neutrophils and clinical outcomes in subgroups.
HRs of HCC patients are reported as (A). HRs of HNC patients are reported as (B). HRs of NSCLC patients are reported as (C). HRs of RCC patients are reported as (D). HRs of Gastric carcinoma patients are reported as (E).
Figure 4
Figure 4. Sensitivity analysis of subgroups.
(A) Sensitivity analysis of studies evaluated intratumoral neutrophils expression on OS. (B) Sensitivity analysis of studies evaluated intratumoral neutrophils expression on RFS/DFS.
See this image and copyright information in PMC

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Grants and funding

The work was supported by Provincial science and technology development plan of Shandong (2012GG0021836), Provincial Natural Science Foundation of Shandong (ZR2013HZ001). FD has received research grant from Health Research Fund of Central Denmark Region and the Danish Cancer Society. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.