SMC 家族成员在 HCC 中的表达谱和预后价值。

Expression profile and prognostic values of SMC family members in HCC.

机构信息

Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.

Department of Surgery, the Johns Hopkins University, Baltimore, MD, USA.

出版信息

Medicine (Baltimore). 2022 Oct 21;101(42):e31336. doi: 10.1097/MD.0000000000031336.

DOI:10.1097/MD.0000000000031336

PMID:36281130

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9592487/

Abstract

OBJECTIVE

The structural maintenance of chromosome (SMC) gene family, including 6 proteins, is involved in a wide range of biological functions in different human cancers. Nevertheless, there is little research on the expression patterns, potential functions and prognostic value of SMC genes in hepatocellular carcinoma (HCC). Based on publicly available databases and integrative bioinformatics analysis, we tried to determine the value of SMC gene expression in predicting the risk of developing HCC.

METHODS

The expression and copy number variations data of SMC family members were obtained from TCGA (The Cancer Genome Atlas). We identified the prognostic values of SMC family members and their clinical features. GSEA (Gene Set Enrichment Analysis) was conducted to detect the mechanism underlying the involvement of SMC family members in liver cancer. We used Tumor Immune Estimation Resource database to explore the associations between TIICs (Tumor Immune Infiltrating Cells) and the SMC family members.

RESULTS

Our analysis proved that downregulation of SMC family members was common modification in HCC patients. In HCC, the expression of SMC1A, SMC2, SMC3, SMC4, SMC6 were upregulated. Upregulation of SMC2, SMC3, and SMC4, along with the clinical stage of HCC, were associated with a poor prognosis according to the results of univariate and multivariate Cox proportional hazards regression analysis. SMC2, SMC3, and SMC4 are also related to tumor purity and immune infiltration levels of HCC. The GSEA results proved that SMC family members take part in numerous biological processes underlying tumorigenesis.

CONCLUSION

In this study, we comprehensively analyzed the expression of SMC family members in patients with HCC. This can provide insights for further investigation of the SMC members as potential therapeutic targets in HCC and suggest that the use of SMC inhibitor targeting SMC2, SMC3, and SMC4 can be a practical strategy for the therapy of HCC.

摘要

目的

结构维持染色体（SMC）基因家族，包括 6 种蛋白质，参与多种不同人类癌症的广泛生物学功能。然而，SMC 基因在肝细胞癌（HCC）中的表达模式、潜在功能和预后价值的研究甚少。本研究基于公开数据库和综合生物信息学分析，试图确定 SMC 基因表达在预测 HCC 发生风险中的价值。

方法

从 TCGA（癌症基因组图谱）中获取 SMC 家族成员的表达和拷贝数变异数据。我们确定了 SMC 家族成员的预后价值及其临床特征。进行 GSEA（基因集富集分析）以检测 SMC 家族成员参与肝癌的潜在机制。我们使用 Tumor Immune Estimation Resource 数据库来探讨 TIICs（肿瘤免疫浸润细胞）与 SMC 家族成员之间的关联。

结果

我们的分析证明 SMC 家族成员的下调在 HCC 患者中是常见的修饰。在 HCC 中，SMC1A、SMC2、SMC3、SMC4 和 SMC6 的表达上调。SMC2、SMC3 和 SMC4 的上调以及 HCC 的临床分期与单变量和多变量 Cox 比例风险回归分析的不良预后相关。SMC2、SMC3 和 SMC4 还与 HCC 的肿瘤纯度和免疫浸润水平有关。GSEA 结果证明 SMC 家族成员参与了肿瘤发生的许多生物学过程。