SULF2 Is a Prognostic Biomarker and Correlated with Tumor Associated Macrophages in Gastric Cancer

Background: Recently, the mutual effects of tumor cells and the tumor immune microenvironment have been identified as key factors in promoting cancer progression. Sulfatase 2 (SULF2) encodes an extracellular endoglucosamine‑6-sulfatase, which could remodel the highly sulfated domains of heparan sulfate. The abnormal expression of SULF2 is reported to play an important role in the carcinogenesis of many kinds of cancer. However, the prognostic value of SULF2 and its correlation with immune cell infiltration in gastric cancer (GC) remain unclear. Results: SULF2 expression was significantly increased in GC compared with gastric normal tissue, especially in the advanced stage GC. In addition, high SULF2 expression significantly predicted an unfavorable prognosis in GC patients (overall survival P=0.0074), particularly who had metastatic lymph nodes. Besides, pathway analyses of SULF2 in GC revealed SULF2 may take part in extracellular structure organization, cell-cell adhesion and proteoglycans in cancer, etc. Importantly, the expression level of SULF2 was found to be positively correlated with the infiltration levels of tumor associated macrophages (TAMs). Moreover, SULF2 expression in GC positively correlated with expression of several immune cell markers, including monocyte markers, TAMs markers and programmed cell death 1 ligand 1 (PD-L1), suggesting its role in regulating tumor immunity.Conclusion: This study identified distinct expression and prognostic values of SULF2 in GC using public databases. Significantly, our findings shed light on the role of SULF2 in GC progression and provided an underlying mechanism that SULF2 expression might modulate tumor immunity by regulating the infiltration of TAMs in GC.