Background The overall prognosis of hepatocellular carcinoma (HCC) is poor and novel prognostic biomarkers might better monitor the progression of HCC. Cell division cycle protein 45 (CDC45) plays a key role in DNA replication and considered to be involved in tumorigenesis. This study investigated CDC45 expression in tumour tissues and defined its prognostic value in HCC patients. Methods We used immunohistochemistry (IHC) staining to examine the expression of CDC45 in tumour tissue specimens and compare them with adjacent normal tissue specimens using a constructed tissue microarray (TMA) and analyzed how clinical features are related to HCC prognosis. Functional enrichment analyses were used to describe significantly involved hallmark pathways of differentially expressed genes (DEGs, which were screened out according to the high or low expression of CDC45 in tumour tissues). Results Our findings showed that the proteome expression of CDC45 was evidently downregulated in HCC tissues compared with matched normal tissues (P < 0.0001). Although we did not find any differences in terms of vascular invasion, metastasis, lymphatic infiltration, or Edmondson grade between patients with high and low CDC45 expression, low CDC45 expression was significantly correlated with microvascular invasion (P = 0.046). Multivariate analysis indicated that CDC45 expression (P = 0.035) was an independent prognostic factor for the overall survival (OS) rate of HCC patients. Patients with CDC45 expression was positively correlated with OS rates among HCC patients (P < 0.05). Functional annotations indicated that CDC45 is involved in the most significant pathways, including the cell cycle, DNA replication, chemical carcinogenesis and drug metabolism–cytochrome P450 pathways. Discussion Our findings showed that low proteomic level of CDC45 was associated with a poor prognosis in HCC patients, indicating that CDC45 might be a novel prognostic marker.

中文翻译：

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细胞分裂周期蛋白 45 表达在肝细胞癌中的预后意义

背景 肝细胞癌 (HCC) 的总体预后较差，新的预后生物标志物可能更好地监测 HCC 的进展。细胞分裂周期蛋白 45 (CDC45) 在 DNA 复制中起关键作用，被认为与肿瘤发生有关。本研究调查了肿瘤组织中 CDC45 的表达，并确定了其在 HCC 患者中的预后价值。方法 我们使用免疫组织化学 (IHC) 染色检查肿瘤组织标本中 CDC45 的表达，并使用构建的组织微阵列 (TMA) 将它们与相邻的正常组织标本进行比较，并分析临床特征与 HCC 预后的关系。功能富集分析用于描述差异表达基因（DEGs，根据肿瘤组织中CDC45的高表达或低表达筛选)。结果我们的研究结果表明，与匹配的正常组织相比，HCC组织中CDC45的蛋白质​​组表达明显下调（P <0.0001）。虽然我们没有发现 CDC45 高表达和低表达的患者在血管浸润、转移、淋巴浸润或 Edmondson 分级方面有任何差异，但 CDC45 低表达与微血管浸润显着相关（P = 0.046）。多变量分析表明，CDC45 表达 (P = 0.035) 是 HCC 患者总生存 (OS) 率的独立预后因素。CDC45表达患者与HCC患者的OS率呈正相关（P < 0.05）。功能注释表明 CDC45 参与了最重要的途径，包括细胞周期、DNA 复制、化学致癌和药物代谢——细胞色素 P450 途径。讨论 我们的研究结果表明，低蛋白质组水平的 CDC45 与 HCC 患者的不良预后相关，表明 CDC45 可能是一种新的预后标志物。