Clinicopathological and Prognostic Significance of SMYD3 in Human Cancers: A Systematic Review and Meta-analysis

Dysregulation of the SET and MYND domain-containing protein 3 (SMYD3) has been found in multiple cancers. This meta-analysis aimed to elucidate the association between SMYD3 expression and clinical outcomes in cancer. A systematic search of Web of Science, Embase, PubMed, Cochrane Library, and CNKI was conducted. The relationship between SMYD3 expression and cancer patients' overall survival (OS) was evaluated using pooled hazard ratios (HRs) and their corresponding confidence intervals (95% CIs). The association between SMYD3 expression and clinicopathological features was assessed using odds ratios (ORs) with 95% CIs, including tumor size, lymph node metastasis (LNM), distance metastasis, and TNM stage. In total, 715 cancer patients with hepatocellular carcinoma, nonsmall cell lung carcinoma, esophageal squamous cell carcinoma, glioma, colorectal cancer, and/or bladder cancer from seven studies were included in our meta-analysis. SMYD3 overexpression was significantly associated with poor OS (HR = 1.81, 95% CI: 1.38-2.37, p < 0.01) with no heterogeneity (I² = 0.0%, p = 0.929) in various cancers. Subgroup analysis showed that the prognostic value of SMYD3 across multiple tumors was constant as the tumor type, sample size, and methods of data extraction changed. Increased SMYD3 expression was positively associated with LNM (OR = 1.88, 95% CI = 1.33-2.66, p < 0.001), tumor size (OR = 1.68, 95% CI: 1.09-2.60, p = 0.019), and advanced TNM stage (OR = 1.84, 95% CI: 1.25-2.69, p = 0.002). Upregulation of SMYD3 was significantly associated with poor prognosis in various cancers, suggesting that SMYD3 may be a useful prognostic biomarker.