Chi Gang, Pei Jinhong, Li Xueqing, Li Xujiong, Pang Hui, Cui Jia, Wu Dongkai, Qu Gexi, He Yuan
Department of Biochemistry, Changzhi Medical College, Changzhi, Shanxi, 046000, China.
Department of Physiology, Changzhi Medical College, Changzhi, Shanxi, 046000, China.
Exp Cell Res. 2022 May 15;414(2):113076. doi: 10.1016/j.yexcr.2022.113076. Epub 2022 Feb 24.
Determining the prognosis of patients remains a challenge due to the phenotypic and molecular diversities of hepatocellular carcinomas (HCC). We aimed to evaluate the role of SMYD5 in HCC. Wilcoxon signed-rank test and logistic regression analyzed the relationship between clinical pathologic features and SMYD5. We found that increased expression of SMYD5 in HCC was closely associated with high histologic grade, stage, T stage and nodal stage. Kaplan-Meier method, Cox regression, univariate analysis and multivariate analysis detected overall survival of TCGA-HCC patients. It turned out that high expression of SMYD5 predicted a worse prognosis in HCC. Gene Set Enrichment Analysis (GSEA) was applied via TCGA data set, which indicated that complement and coagulation cascades, fatty acid metabolism, primary bile acid biosynthesis, drug metabolism cytochrome P450, PPAR signaling pathway and retinol metabolism were differentially enriched in SMYD5 high expression phenotype. Interestingly, we proved that SMYD5 upregulation in HCC cells was induced by promoter hypo-methylation. Moreover, functional experiments demonstrated that SMYD5 silencing abrogated cell proliferation, migration and invasion and enhanced paclitaxel sensitivity in HCC. All findings implied that SMYD5 might be an underlying biomarker for prognosis and treatment of HCC.
由于肝细胞癌（HCC）的表型和分子多样性，确定患者的预后仍然是一项挑战。我们旨在评估SMYD5在HCC中的作用。Wilcoxon符号秩检验和逻辑回归分析了临床病理特征与SMYD5之间的关系。我们发现，HCC中SMYD5表达增加与高组织学分级、分期、T分期和淋巴结分期密切相关。Kaplan-Meier法、Cox回归、单因素分析和多因素分析检测了TCGA-HCC患者的总生存期。结果表明，SMYD5高表达预示着HCC患者预后较差。通过TCGA数据集进行基因集富集分析（GSEA），结果表明补体和凝血级联反应、脂肪酸代谢、初级胆汁酸生物合成、药物代谢细胞色素P450、PPAR信号通路和视黄醇代谢在SMYD5高表达表型中存在差异富集。有趣的是，我们证明了HCC细胞中SMYD5上调是由启动子低甲基化诱导的。此外，功能实验表明，SMYD5沉默可消除HCC细胞的增殖、迁移和侵袭，并增强其对紫杉醇的敏感性。所有研究结果表明，SMYD5可能是HCC预后和治疗的潜在生物标志物。
