Clinicopathologic and prognostic significance of tumor-associated macrophages in patients with hepatocellular carcinoma: A meta-analysis.

Wei Ding,Yibo Wang,Yulin Tan,Xuezhong Xu,Wenbo Xue,Yan Qian,Peng Jiang,Jung Weon Lee

doi:10.1371/journal.pone.0223971

Wei Ding, Yibo Wang + Show 6 more

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https://doi.org/10.1371/journal.pone.0223971

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Abstract

Tumor-associated macrophages (TAMs) deserve more focus because of its clinicopathologic and prognostic roles in solid tumors. However, the prognostic value of TAMs in patients with hepatocellular carcinoma (HCC) is still controversial. We performed a meta-analysis to resolve the issue. We selected relevant studies from the Cochrane Library, Embase and PubMed databases. The hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated employing fixed-effect or random-effect models depending on the heterogeneity of the included trials. Moreover, we also performed subgroup analysis, cumulative meta-analysis, sensitivity analysis, and bias analysis (Egger's test). A total of 20 observational studies with 4297 patients were enrolled. For TAMs subsets, high density of CD68+ TAMs in either intratumor (IT) (pooled HR = 1.417; 95% CI = 1.092-1.839; P = 0.009) or peritumor (PT) (pooled HR = 1.393; 95% CI = 1.022-1.899; P = 0.036) was associated with a poor OS. High density of CD68+ TAMs in IT was also associated with high AFP value, large tumor size, absent encapsulation, present vascular invasion, and later tumor-nodes-metastasis (TNM) stage. High density of CD163+ macrophages in serum was associated with a poor OS (pooled HR = 5.698; 95% CI = 3.062-10.603; P < 0.001). High density of CD204+ TAMs in IT was associated with a poor OS (pooled HR = 1.947; 95% CI = 1.387-2.733; P < 0.001. High density of CD206+ TAMs in IT was associated with a poor OS (pooled HR = 1.723; 95% CI = 1.308-2.270; P < 0.001) and DFS (pooled HR = 1.711; 95% CI = 1.214-2.412; P = 0.002). However, high density of CD169+ TAMs in IT was associated with a good OS (pooled HR = 0.471; 95% CI = 0.343-0.647; P = 0.037). TAMs could serve as independent predictive indicators and therapeutic targets for HCC. Further trials are needed to elucidate the exact relationship and the underlying mechanism.

Highlights

Hepatocellular carcinoma (HCC) is the fifth most common malignant tumor in the world with approximately 850,000 new cases every year and represents the third leading cause of global cancer deaths and the incidence is raising [1, 2]
For Tumor-associated macrophages (TAMs) subsets, high density of CD68+ TAMs in either intratumor (IT) or peritumor (PT) was associated with a poor overall survival (OS)
High density of CD163+ macrophages in serum was associated with a poor OS

Summary

Introduction

Hepatocellular carcinoma (HCC) is the fifth most common malignant tumor in the world with approximately 850,000 new cases every year and represents the third leading cause of global cancer deaths and the incidence is raising [1, 2]. Surgical resection is the primary therapy for HCC. Transcatheter arterial chemoembolization was taken as effective supplement measure to prevent or reduce the recurrence, especially for high risk liver cancer. Radiofrequency ablation, targeted medical therapy and Chinese medicinal therapy were choices for advanced liver cancer [3]. High rates of recurrence and metastasis after liver resection result in poor prognosis. Diagnosis and comprehensive treatment in time can increase the efficacy of HCC. It is critical to explore and validate new markers of HCC with high sensitivity and specificity

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