Abundance of CD163-Positive Tumor-Associated Macrophages in the Early Gastric Cancer Predicts the Recurrence after Curative Resection

Background: We aimed to investigate the prognostic value of M2 macrophages to predict the recurrence of early gastric cancer (EGC). Methods: A retrospective analysis was carried out among EGC patients (95 non-recurrence and 78 recurrence) who underwent surgery at Luhe People's Hospital of Nanjing. A 5-year recurrence status was utilized to classify the patients into the recurrence group and non-recurrence group. CD163 and proliferating cell nuclear antigen were utilized as markers to detect M2 macrophages and proliferation. Cumulative tumor recurrence curve was adopted to analyze the association between the number of tumor-associated macrophages (TAMs) and the recurrence of EGC. Colony formation and invasion abilities of MKN45 (JCRB0254, human gastric epithelial cell line) with or without M2 macrophage coculture were detected in vitro, and the xenograft model was utilized to detect in vivo effect of M2 macrophages on tumor growth. Results: The number of CD163(+) macrophages and expression of transforming growth factor-beta 1, matrix metallopeptidase 9, and vascular endothelial growth factor A were significantly different between the EGC recurrence and non-recurrence group. The cumulative tumor recurrence rate was found to be dependent on the infiltration number of TAMs. M2 macrophages promoted the proliferation and invasion of human MKN45 cells in vitro, as well as tumor growth in the xenograft model. Conclusion: The abundance of CD163(+)-positive TAMs in EGC predicts the recurrence after curative resection.