SMYD Family Members Serve as Potential Prognostic Markers and Correlate with Immune Infiltrates in Gastric Cancer

BACKGROUND: The SMYD family comprises a group of genes encoding lysine methyltransferases, which are closely related to tumorigenesis. However, a systematic understanding of their role in gastric cancer (GC) is lacking. METHODS: Using databases and tools such as the Cancer Genome Atlas, Human Protein Atlas, Kaplan–Meier Plotter, Gene Expression Profiling Interactive Analysis, and Metascape, we comprehensively analyzed differences in SMYD expression and its prognostic value as well as the association of SMYDs with immune cell infiltration, tumor mutational burden (TMB), and microsatellite instability (MSI). We conducted functional enrichment analysis and explored a competing endogenous RNA mechanism regulating SMYD mRNA and protein levels in patients with GC. RESULTS: In GC, the expression of SMYD2/3/4/5 mRNA was significantly upregulated, as opposed to that of SMYD1 mRNA, which was significantly downregulated. The protein levels of SMYDs were consistent with mRNA levels. SMYD1/2/4/5 was negatively correlated with overall survival; SMYD1/2/3/5 was negatively correlated with progression-free survival. Our SMYD-based signature and nomogram model may be useful for inferring the prognosis of GC. All SMYDs were closely associated with the infiltration of six immune cell types: uncharacterized, CD8(+)T, CD4(+)T, macrophage, endothelial, and B cells. TMB was significantly negatively correlated with SMYD1 expression, while a significant positive correlation was observed with SMYD2/5. Furthermore, MSI was significantly positively correlated with SMYD2/5 expression. Long non-coding RNAs, such as chr22-38_28785274-29006793.1, XLOC_002309, and CTD-2008N3.1, were suggested to regulate SMYD expression by sponging multiple microRNAs. CONCLUSION: SMYDs are differentially expressed in GC and are thus potential prognostic markers. SMYD expression is closely related to immune infiltration, TMB, and MSI, all of which are closely related to the response to targeted immune therapy.