Background: CD47 has been identified as an innate immune checkpoint and found to be associated with inferior survival in various types of cancer. However, the critical role of CD47 in gastric cancer and its association with tumor associated macrophages remain unclear.
Methods: Tumor tissues of gastric cancer from Zhongshan Hospital and data from GSE62254, GSE84437 and TCGA datasets were analyzed. Immunohistochemistry was performed to detect the expression of CD47, CD11c, CD163 and CD68 in gastric cancer tissues. Kaplan-Meier curves and Cox model were used for comparing the clinical outcomes of patients belonging to different subgroups.
Results: Gastric cancer patients with high CD47 expression exhibited poor prognosis and inferior therapeutic responsiveness to fluorouracil-based adjuvant chemotherapy (ACT). A positive correlation was found between M1-polarized macrophage infiltration and CD47 expression in gastric cancer; however, the prognostic value of M1-polarized macrophages was attenuated in CD47-high gastric cancer patients. Moreover, we found that CD47 mRNA level was enriched in microsatellite-instable (MSI) subtype of gastric cancer and associated with ARID1A mutation and FGFR2 signaling pathway activation.
Conclusions: Aberrant CD47 expression represented an independent predictor for adverse survival outcome and ACT resistance in gastric cancer. Targeting CD47 might be a promising strategy for gastric cancer patients.
Keywords: Adjuvant chemotherapy; CD47; Gastric cancer; Prognosis; Tumor-associated macrophage.