Liu Mingjiang, Yu Jingjing, Jin Hu, Wang Sifan, Ding Jin, Xing Hao, He Songqing, Zeng Yonglian
Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi, People's Republic of China.
Onco Targets Ther. 2021 Apr 15;14:2635-2649. doi: 10.2147/OTT.S298616. eCollection 2021.
Hepatocellular carcinoma (HCC) is a highly malignant and common tumor. Many biomarkers have been identified for HCC. However, the available ones are not accurate enough in term of prognostic value and new markers are needed for the prognosis of this disease. Sirtuins are NAD-dependent histone deacetylases involved in many biological processes of cancers, consisting of family members SIRT1-SIRT7. However, the prognostic value of the SIRTs in HCC remains largely unknown.
Differential expression of SIRTs and survival analysis were assessed in patients with HCC using Oncomine and UALCAN databases. Gene set enrichment analysis (GSEA) was used for pathway analysis. Metascape software was used to construct gene ontologies, metabolic pathways and protein-protein interaction networks. Moreover, a HCC murine model was used to validate the expression levels of SIRT3/6/7 expression.
Differential expression analysis suggested that SIRT2-7, not SIRT1, were expressed at higher levels in HCC tissues compared to adjacent normal tissues. These SIRTs showed some similarities, as revealed by GO and KEGG pathway. Higher SIRT3/6/7 mRNA expression levels were found to be significantly associated with shorter overall survival (OS) in HCC patients. Both SIRT3/6/7 mRNA and protein levels were highly expressed in HCC. In addition, over-expression of SIRT3/6/7 was associated with tumor stage and grade in HCC patients. Univariate analysis showed that SIRT 6/7 expressions were linked to a shorter OS of HCC patients. Multivariate analysis showed that SIRT7 levels were independently associated with a significantly shorter OS in HCC patients.
Differentially expressed SIRT3/6/7 were significantly associated with tumor stage, grade and OS in HCC patients. In addition, SIRT7 were independently associated with a significantly shorter OS in HCC patients. Thus, SIRT3/6/7 can be used as prognostic biomarkers to predict the survival of HCC patients.
肝细胞癌（HCC）是一种高度恶性的常见肿瘤。已鉴定出许多用于HCC的生物标志物。然而，就预后价值而言，现有的生物标志物不够准确，需要新的标志物来预测该疾病的预后。沉默调节蛋白是依赖烟酰胺腺嘌呤二核苷酸（NAD）的组蛋白脱乙酰酶，参与癌症的许多生物学过程，由SIRT1 - SIRT7家族成员组成。然而，沉默调节蛋白在HCC中的预后价值仍 largely未知。
使用Oncomine和UALCAN数据库评估HCC患者中沉默调节蛋白的差异表达和生存分析。基因集富集分析（GSEA）用于通路分析。Metascape软件用于构建基因本体、代谢途径和蛋白质 - 蛋白质相互作用网络。此外，使用HCC小鼠模型验证SIRT3/6/7的表达水平。
差异表达分析表明，与相邻正常组织相比，HCC组织中SIRT2 - 7而非SIRT1表达水平更高。这些沉默调节蛋白显示出一些相似性，如基因本体（GO）和京都基因与基因组百科全书（KEGG）通路所揭示的那样。发现较高的SIRT3/6/7 mRNA表达水平与HCC患者较短的总生存期（OS）显著相关。SIRT3/6/7的mRNA和蛋白质水平在HCC中均高表达。此外，SIRT3/6/7的过表达与HCC患者的肿瘤分期和分级相关。单因素分析表明，SIRT6/7的表达与HCC患者较短的OS相关。多因素分析表明，SIRT7水平与HCC患者显著较短的OS独立相关。
差异表达的SIRT3/6/7与HCC患者的肿瘤分期、分级和OS显著相关。此外，SIRT7与HCC患者显著较短的OS独立相关。因此，SIRT3/6/7可作为预后生物标志物来预测HCC患者的生存期。
