The copper metabolism MURR1 domain (COMMD) protein family involved in tumor development and progression in several types of human cancer, but little is known about the function of COMMD proteins in hepatocellular carcinoma (HCC). The ONCOMINE and the UALCAN databases were used to evaluate the expression of COMMD1–10 in HCC and the association of this family with individual cancer stage and tumor grade. Kaplan-Meier (K-M) Plotter and Cox analysis hint the prognostic value of COMMDs. A network comprising 50 most similar genes and COMMD1–10 was constructed with the STRING database. Gene set enrichment analysis (GSEA) was performed using LinkedOmics database. The correlations between COMMD expression and the presence of immune infiltrating cells were also analyzed by the tumor immune estimation resource (TIMER) database. GSE14520 dataset and 80 HCC patients were used to validated the expression and survival value of COMMD3. Human HCC cell lines were also used for validating the function of COMMD3. The expression of all COMMD family members showed higher expression in HCC tissues than that in normal tissues, and is associated with clinical cancer stage and pathological tumor grade. In HCC patients, the transcriptional levels of COMMD1/4 are positively correlated with overall survival (OS), while those of COMMD2/3/7/8/9 are negatively correlated with OS. Multivariate analysis indicated that a high level of COMMD3 mRNA is an independent prognostic factor for shorter OS in HCC patients. However, the subset of patients with grade 3 HCC, K-M survival curves revealed that high COMMD3/5/7/8/9 expression and low COMMD4/10 expression were associated with shorter OS. In addition, the expression of COMMD2/3/10 was associated with tumor-induced immune response activation and immune infiltration in HCC. The expression of COMMD3 from GSE14520 dataset and 80 patients are both higher in tumor than that in normal tissue, and a higher level of COMMD3 mRNA is associated with shorter OS. Knockdown of COMMD3 inhibits human HCC cell lines proliferation in vitro. Our study indicates that COMMD3 is an independent prognostic biomarker for the survival of HCC patients. COMMD3 supports the proliferation of HCC cells and contributes to the poor OS in HCC patients.

中文翻译：

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COMMD蛋白家族在肝细胞癌中的表达、预后价值及免疫浸润活性的转录分析

铜代谢 MURR1 结构域 (COMMD) 蛋白家族参与多种类型人类癌症的肿瘤发展和进展，但对 COMMD 蛋白在肝细胞癌 (HCC) 中的功能知之甚少。ONCOMINE 和 UALCAN 数据库用于评估 COMMD1-10 在 HCC 中的表达以及该家族与个体癌症分期和肿瘤分级的关联。Kaplan-Meier (KM) 绘图仪和 Cox 分析提示了 COMMD 的预后价值。使用 STRING 数据库构建了一个包含 50 个最相似基因和 COMMD1-10 的网络。使用 LinkedOmics 数据库进行基因集富集分析 (GSEA)。COMMD 表达与免疫浸润细胞的存在之间的相关性还通过肿瘤免疫估计资源（TIMER）数据库进行了分析。使用 GSE14520 数据集和 80 名 HCC 患者验证 COMMD3 的表达和存活值。人类 HCC 细胞系也用于验证 COMMD3 的功能。所有COMMD家族成员在HCC组织中的表达均高于正常组织，并与临床癌症分期和病理肿瘤分级相关。在HCC患者中，COMMD1/4的转录水平与总生存期（OS）呈正相关，而COMMD2/3/7/8/9的转录水平与OS呈负相关。多变量分析表明，高水平的 COMMD3 mRNA 是 HCC 患者 OS 较短的独立预后因素。然而，3 级 HCC 患者的亚组 KM 生存曲线显示，高 COMMD3/5/7/8/9 表达和低 COMMD4/10 表达与较短的 OS 相关。此外，COMMD2/3/10 的表达与 HCC 中肿瘤诱导的免疫反应激活和免疫浸润有关。GSE14520数据集和80例患者COMMD3在肿瘤中的表达均高于正常组织，COMMD3 mRNA水平较高与较短的OS相关。COMMD3 的敲低在体外抑制人 HCC 细胞系增殖。我们的研究表明 COMMD3 是 HCC 患者生存的独立预后生物标志物。COMMD3 支持 HCC 细胞的增殖并导致 HCC 患者的 OS 较差。并且较高水平的 COMMD3 mRNA 与较短的 OS 相关。COMMD3 的敲低在体外抑制人 HCC 细胞系增殖。我们的研究表明 COMMD3 是 HCC 患者生存的独立预后生物标志物。COMMD3 支持 HCC 细胞的增殖并导致 HCC 患者的 OS 较差。并且较高水平的 COMMD3 mRNA 与较短的 OS 相关。COMMD3 的敲低在体外抑制人 HCC 细胞系增殖。我们的研究表明 COMMD3 是 HCC 患者生存的独立预后生物标志物。COMMD3 支持 HCC 细胞的增殖并导致 HCC 患者的 OS 较差。