Clinical prognostic value of the SMYD2/3 as new epigenetic biomarkers in solid cancer patients: a systematic review and meta-analysis.

BACKGROUND: Suppressor of variegation, Enhancer of Zeste, Trithorax (SET) and Myeloid-Nervy-DEAF1 (MYND) domain-containing protein (SMYD) family with methyltransferase activity is involved in cancer progression. This novel meta-analysis aimed to evaluate the association of SMYD family with the clinical and survival outcomes in solid cancer patients.

METHODS: We systematically searched Embase, PubMed, Scopus and Web of Science to select relevant articles. Hazard ratios (HRs), odds ratios (ORs) and 95% confidence intervals were extracted. Heterogeneity was evaluated by chi-square-based Q and I2 tests, while publication bias by funnel plots and Egger's test. Seven subcategories were used to perform subgroup analyses.

RESULTS: 32 articles (4,826 patients) met inclusion criteria. SMYD2/3 overexpression was statistically associated with poor overall survival (HR=1.794, P<0.001 ), disease/relapse/progression-free survival (HR=2.114, P<0.001 ), disease/cancer-specific survival (HR=3.220, 95%CI:1.498-6.921, P=0.003 ), larger tumor size (OR=1.963, P<0.001 ), advanced TNM stage (OR=2.066, P<0.001 ), lymph node metastasis (OR=2.054, P<0.001 ), and distant metastasis (OR=1.978, P= 0.004). Subgroup analysis showed more significant association between SMYD2 overexpression and reduced survival outcomes than that in SMYD3. Conversely, the relationship between SMYD3 and various clinicopathologic factors was stronger compared to SMYD2.

CONCLUSION: Enhanced SMYD2/3 expression may be an unfavorable clinical prognostic factor in different solid cancer types, being linked to tumor development, poor survival outcomes and high likelihood of metastasis.