The Prognostic and Clinicopathological Significance of Tumor-Associated Macrophages in Patients with Gastric Cancer: A Meta-Analysis

PLoS One. 2017 Jan 12;12(1):e0170042. doi: 10.1371/journal.pone.0170042. eCollection 2017.

Abstract

Objective: Comprehensive studies have investigated the prognostic and clinicopathological value of tumor-associated macrophages (TAMs) in gastric cancer patients, yet results remain controversial. Therefore, we performed a meta-analysis to clarify this issue.

Methods: PubMed, Embase, and the Cochrane Library databases were searched to identify eligible studies. We extracted hazard ratios (HRs) and odds ratios (ORs) with their corresponding 95% confidence intervals (95% CIs) to estimate the effect sizes. In addition, subgroup analysis and sensitivity analysis were also conducted.

Results: A total of 19 studies involving 2242 patients were included. High generalised TAMs density was significantly associated with poor overall survival (OS) (HR 1.49, 95% CI 1.15-1.95). Subgroup analysis revealed that CD68+ TAMs had no significant effect on OS (HR 1.38, 95% CI 1.00-1.91). High M1 TAMs density was correlated with better OS (HR 0.45, 95% CI 0.32-0.65). By contrast, high density of M2 TAMs was correlated with a poor prognosis for OS (HR 1.48, 95% CI 1.25-1.75). Furthermore, high M2 TAMs density was correlated with larger tumor size, diffuse Lauren type, poor histologic differentiation, deeper tumor invasion, lymph node metastasis, and advanced TNM stage.

Conclusions: Overall, this meta-analysis reveal that although CD68+ TAMs infiltration has the neutral prognostic effects on OS, the M1/M2 polarization of TAMs are predicative factor of prognosis in gastric cancer patients.

Publication types

  • Meta-Analysis

MeSH terms

  • Antigens, CD / metabolism
  • Antigens, Differentiation, Myelomonocytic / metabolism
  • Databases, Factual
  • Humans
  • Lymphatic Metastasis
  • Macrophages / immunology
  • Macrophages / pathology*
  • Neoplasm Staging
  • Odds Ratio
  • Prognosis
  • Proportional Hazards Models
  • Stomach Neoplasms / diagnosis*
  • Stomach Neoplasms / mortality
  • Stomach Neoplasms / pathology
  • Survival Analysis

Substances

  • Antigens, CD
  • Antigens, Differentiation, Myelomonocytic
  • CD68 antigen, human

Grants and funding

This work was supported by National Natural Science Foundation of China (No. 81372550); and Key Laboratory Programme of Liaoning Province (LZ2015080). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.