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. 2017 Feb 10;8(3):363-370.
doi: 10.7150/jca.16730. eCollection 2017.

High Infiltration of Polarized CD163+ Tumor-Associated Macrophages Correlates with Aberrant Expressions of CSCs Markers, and Predicts Prognosis in Patients with Recurrent Gastric Cancer

Wei-Jie Zhang  1 , Zhi-Hua Zhou  2 , Ming Guo  3 , Liu-Qing Yang  4 , Yuan-Yuan Xu  4 , Tao-Hong Pang  4 , Shan-Ting Gao  5 , Xin-Yun Xu  6 , Qi Sun  6 , Min Feng  1 , Hao Wang  1 , Chun-Lei Lu  7 , Guo-Zhong Wu  7 , Wen-Xian Guan  1 , Gui-Fang Xu  4
Affiliations

High Infiltration of Polarized CD163+ Tumor-Associated Macrophages Correlates with Aberrant Expressions of CSCs Markers, and Predicts Prognosis in Patients with Recurrent Gastric Cancer

Wei-Jie Zhang et al. J Cancer. .

Abstract

Background: As the most predominant tumor-infiltrating immune cells, tumor-associated macrophages (TAMs) are associated with poor outcome in multiple solid cancers and play important roles in cancer progression. Cancer stem cells (CSCs) may account for metastasis and recurrence after cancer therapy. However, the association between TAMs and CSCs is not clarified in gastric cancer (GC). The aim of the present study was to evaluate the effects of TAMs on CSCs in GC and find out the risk factors to predict recurrence and prognosis. Material and methods: This study included consecutive 236 patients with histologically confirmed primary GC. TAMs marker CD163 and CSCs-related proteins were detected by immunohistochemistry (IHC) in GC tissues and their prognostic values were all investigated. Results: High expression of CD163+ TAMs was found in patents with aggressive characteristics, especially for patents with recurrence. There existed a significant correlation between high expression of CD163 and CSCs-related markers in GC tissues. In patients with recurrence, high-expression of CD163 TAMs was an independent worse prognostic factor. Conclusion: High infiltration of TAMs was related to aggressive behavior, associated with aberrant expression of CSC markers, and an independent worse prognostic factor in GC. Targeting TAMs may be a potential treatment strategy for GC, including patients with recurrence.

Keywords: Cancer stem cells (CSCs); Gastric cancer; Prognosis.; Recurrent; Tumor-associated macrophages (TAMs).

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interest exists.

Figures

Figure 1
Figure 1
Detection of CD163, CSCs markers CD44 and CD133 expression in GC tissue and adjacent normal tissue by IHC. Strong CD163 immunoreactivity was identified in poorly differentiated cancer. CD44 and CD133 expression was barely seen in normal tissue but was observed in GC tissue. GC=gastric cancer, IHC=immunohistochemistry.
Figure 2
Figure 2
Pattern of recurrence of after curative gastrectomy.
Figure 3
Figure 3
Expression of CD163 and associated CSCs proteins predict poor prognosis of GC. Patients that high expression of CD163 demonstrated shorter DSS and OS than those with low expressed (P<0.001). Patients with high expression levels of CSCs markers CD44 and CD133 had a worse OS than those with low CSCs markers (P<0.005). As for cases with recurrent, patients with high positive CD163 exhibited poor survival rates compared with those who were negative or low for CD163 (P<0.005). GC=gastric cancer, DSS=disease-specific survival, OS=overall survival.
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