Abstract
Gastric cancer (GC) is the fifth most common cancer globally. Secreted frizzled-related proteins (SFRP) are important elements associated with the Wnt signaling pathway, and its dysregulated expression is found in multiple cancers. However, the function of distinct SFRPs in GC remains poorly understood. We investigated the differential expression, prognostic value, and immune cell infiltration of SFRPs in gastric cancer patients from the Oncomine, Gene Expression Profiling Interactive Analysis (GEPIA), UALCAN, Kaplan–Meier plotter, cBioPortal, STRING, Gene-MANIA, DAVID, MethSurv, and TIMER databases. We found that the expression levels of SFRP2 and SFRP4 were significantly increased in GC tissues, whereas the SFRP1 and SFRP5 expressions were reduced. SFRP1, SFRP2, and SFRP5 were significantly correlated with the clinical cancer stage in GC patients. Higher expression of SFRPs was associated with short overall survival (OS) in GC patients. Besides, high SFRPs methylation showed favorable OS in GC patients. The functions of SFRPs were primarily related to the Wnt signaling pathway, immune system development, and basal cell carcinoma. The expression of SFRPs was strongly correlated with immune infiltrating cells, including CD4+ T cells and macrophages in GC. Our study indicated that SFRPs could be potential targets of precision therapy and prognostic biomarkers for the survival of GC patients.
Highlights
The results showed that the expression levels of SFRP2 and SFRP4 in Gastric cancer (GC) tissues were higher than those in normal tissues, and the expression levels of SFRP1 and SFRP5 were lower in gastric tissues than in normal tissues
We found that the expression of SFRP2/3/4 was higher in gastric adenocarcinoma of not otherwise specified (NOS) and diffuse type, and gastric intestinal adenocarcinoma of mucinous type
We found that the expression of SFRP2 and SFRP4 in GC tissues was higher than that in normal tissues, while the expression of SFRP1 was decreased in GC tissues in the ONCOMINE database and UALCAN database
Summary
Gastric cancer (GC) is the fifth most common malignant tumor and is the second leading cause of cancer-associated mortality worldwide according to the GLOBOCAN 2018 estimation [1]. Despite advances in the diagnosis and treatment of cancer, the prognosis of gastric cancer remains unsatisfactory due to the low diagnosis rate, with a 5-year overall survival lower than 40% [2]. The exploration of a sensitive and specific biomarker that could predict the prognosis is crucial for GC management. Secreted frizzled-related proteins (SFRPs) are extracellular tumor suppressor genes of
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