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

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

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.

Publication types

  • Evaluation Study
  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Systematic Review

MeSH terms

  • Antigens, CD / genetics
  • Antigens, CD / metabolism*
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Cell Adhesion Molecules / genetics
  • Cell Adhesion Molecules / metabolism*
  • GPI-Linked Proteins / genetics
  • GPI-Linked Proteins / metabolism
  • Humans
  • Lewis X Antigen / genetics
  • Lewis X Antigen / metabolism*
  • Neoplasms / diagnosis*
  • Neutrophils / metabolism*
  • Predictive Value of Tests
  • Prognosis

Substances

  • Antigens, CD
  • Biomarkers, Tumor
  • CEACAM8 protein, human
  • Cell Adhesion Molecules
  • GPI-Linked Proteins
  • Lewis X Antigen