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

PurposeTumor-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.MethodsWe 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).ResultsA 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 ConclusionsTAMs could serve as independent predictive indicators and therapeutic targets for HCC. Further trials are needed to elucidate the exact relationship and the underlying mechanism.

研究背景 肿瘤相关巨噬细胞（Tumor-associated macrophages, TAMs）因在实体瘤中具有重要的临床病理与预后作用而受到广泛关注。然而，TAMs在肝细胞癌（hepatocellular carcinoma, HCC）患者中的预后价值仍存在争议。本研究通过开展荟萃分析以解决这一争议。
方法 我们从Cochrane图书馆、Embase及PubMed数据库中检索相关研究。根据纳入研究的异质性，采用固定效应模型或随机效应模型计算风险比（hazard ratios, HRs）与95%置信区间（confidence intervals, CIs）。此外，本研究还进行了亚组分析、累积荟萃分析、敏感性分析以及偏倚分析（Egger’s test）。
结果 本研究共纳入20项观察性研究，涉及4297例患者。针对TAMs亚群，瘤内（intratumor, IT）区域高浸润的CD68阳性TAMs（合并HR=1.417；95%CI=1.092~1.839；P=0.009）或瘤周（peritumor, PT）区域高浸润的CD68阳性TAMs（合并HR=1.393；95%CI=1.022~1.899；P=0.036）均与不良总生存期（overall survival, OS）相关。瘤内高浸润的CD68阳性TAMs同时还与高甲胎蛋白（alpha-fetoprotein, AFP）水平、较大肿瘤体积、无包膜、存在血管侵犯以及较晚的肿瘤-淋巴结-转移（tumor-nodes-metastasis, TNM）分期相关。血清中高密度的CD163阳性巨噬细胞与不良总生存期相关（合并HR=5.698；95%CI=3.062~10.603；P
结论 TAMs可作为肝细胞癌的独立预测指标与治疗靶点。未来仍需开展更多研究以阐明二者间的确切关联及潜在作用机制。