Abstract
BackgroundThe SET and MYND domain-containing (SMYD) gene family comprises a set of genes encoding lysine methyltransferases. This study aimed to clarify the relationship between the expression levels of SMYD family members and the prognosis and immune infiltration of malignant tumors of the digestive system.MethodsThe Oncomine, Ualcan, Kaplan–Meier Plotter, cBioPortal, Metascape, and TIMER databases and tools were used to analyze the correlation of SMYD family mRNA expression, clinical stage, TP53 mutation status, prognostic value, gene mutation, and immune infiltration in patients with esophageal carcinoma (ESCA), liver hepatocellular carcinoma (LIHC), and stomach adenocarcinoma (STAD).ResultsIn ESCA, the mRNA expression of SMYD2/3/4/5 was significantly correlated with the incidence rate, that of SMYD2/3 with the clinical stage, that of SMYD2/3/4/5 with TP53 mutation status, that of SMYD2/4/5 with overall survival (OS), and that of SMYD1/2/3/4 with relapse-free survival (RFS). In LIHC, the mRNA expression of SMYD1/2/3/4/5 was significantly correlated with the incidence rate, that of SMYD2/4/5 with the clinical stage, that of SMYD3/5 with TP53 mutation status, that of SMYD2/3/4/5 with OS, and that of SMYD3/5 with RFS. In STAD, the mRNA expression of SMYD2/3/4/5 was significantly correlated with the incidence rate, that of SMYD1/4 with the clinical stage, that of SMYD1/2/3/5 with TP53 mutation status, that of SMYD1/3/4 with OS, and that of SMYD1/3 with RFS. Furthermore, the function of SMYD family mutation-related genes in ESCA, LIHC, and STAD patients was mainly related to pathways, such as mitochondrial gene expression, mitochondrial matrix, and mitochondrial translation. The expression of SMYD family genes was significantly correlated with the infiltration of six immune cell types and eight types of immune check sites.ConclusionSMYD family genes are differentially expressed and frequently mutated in malignant tumors of the digestive system (ESCA, LIHC, and gastric cancer). They are potential markers for prognostic prediction and have important significance in immunity and targeted therapy.
Highlights
Esophageal carcinoma (ESCA), liver hepatocellular carcinoma (LIHC) and gastric cancer (GC) are the main malignant tumors of the digestive system, accounting, respectively, for 5.3, 8.2, and 8.2% of cancer-related deaths worldwide (Bray et al, 2018)
According to the information from ten data sets, SMYD1 was significantly downregulated in GC patients (D’Errico et al, 2009), SMYD2 was significantly upregulated in LIHC patients (Chen et al, 2002; Wurmbach et al, 2007; Mas et al, 2009; Roessler et al, 2010), and significantly upregulated in GC patients (Chen et al, 2003; D’Errico et al, 2009; Wang et al, 2012)
SMYD3 was significantly overexpressed in ESCA and LIHC patients (Wurmbach et al, 2007; Hu et al, 2010; Kim et al, 2010; Roessler et al, 2010; Su et al, 2011), whereas SMYD4 and SMYD5 were significantly overexpressed in GC patients (D’Errico et al, 2009; Wang et al, 2012; Table 1)
Summary
Esophageal carcinoma (ESCA), liver hepatocellular carcinoma (LIHC) and gastric cancer (GC) are the main malignant tumors of the digestive system, accounting, respectively, for 5.3, 8.2, and 8.2% of cancer-related deaths worldwide (Bray et al, 2018). Their prevention and treatment should attract substantial attention. Previous studies have shown that some SMYD family members are differentially expressed in GC and related to prognosis. This study aimed to clarify the relationship between the expression levels of SMYD family members and the prognosis and immune infiltration of malignant tumors of the digestive system
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