Department of Biochemistry, Changzhi Medical College, Changzhi, 046000, Shanxi, China.
BMC Bioinformatics. 2022 Jun 24;23(1):252. doi: 10.1186/s12859-022-04806-8.
Hepatocellular carcinoma (HCC) is a primary malignant tumor that accounts for approximately 90% of all cases of primary liver cancer worldwide. Microtubule alterations may contribute to the broad spectrum of resistance to chemotherapy, tumor development, and cell survival. This study aimed to assess the value of ribonucleic acid export 1 (RAE1), as a regulator of microtubules, in the diagnosis and prognosis of HCC, and to analyze its correlation with genetic mutations and pathways in HCC.
The mRNA and protein levels of RAE1 were significantly elevated in HCC tissues compared with those in normal tissues. The high expression level of RAE1 was correlated with T stage, pathologic stage, tumor status, histologic grade, and alpha-fetoprotein level. HCC patients with a higher expression level of RAE1 had a poorer prognosis, and the expression level of RAE1 showed the ability to accurately distinguish tumor tissues from normal tissues (area under the curve (AUC) = 0.951). The AUC values of 1-, 3-, and 5-year survival rates were all above 0.6. The multivariate Cox regression analysis showed that RAE1 expression level was an independent prognostic factor for a shorter overall survival of HCC patients. The rate of RAE1 genetic alterations was 1.1% in HCC samples. Gene ontology and kyoto encyclopedia of genes and genomes pathway enrichment analyses indicated the co-expressed genes of RAE1 were mainly related to chromosome segregation, DNA replication, and cell cycle checkpoint. Protein-protein interaction analysis showed that RAE1 was closely correlated with NUP205, NUP155, NUP214, NUP54, and NXF1, all playing important roles in cell division and mitotic checkpoint.
RAE1 can be a potential diagnostic and prognostic biomarker associated with microtubules and a therapeutic target for HCC.
肝细胞癌(HCC)是一种原发性恶性肿瘤,约占全球原发性肝癌的 90%。微管的改变可能导致化疗、肿瘤发展和细胞存活的广谱耐药性。本研究旨在评估微管调节因子核糖核酸输出因子 1(RAE1)在 HCC 的诊断和预后中的价值,并分析其与 HCC 中的基因突变和途径的相关性。
与正常组织相比,RAE1 的 mRNA 和蛋白水平在 HCC 组织中显著升高。RAE1 的高表达水平与 T 分期、病理分期、肿瘤状态、组织学分级和甲胎蛋白水平有关。RAE1 表达水平较高的 HCC 患者预后较差,RAE1 的表达水平能够准确区分肿瘤组织和正常组织(曲线下面积(AUC)=0.951)。1 年、3 年和 5 年生存率的 AUC 值均高于 0.6。多因素 Cox 回归分析表明,RAE1 表达水平是 HCC 患者总体生存率较短的独立预后因素。在 HCC 样本中,RAE1 基因改变的发生率为 1.1%。基因本体和京都基因与基因组百科全书通路富集分析表明,RAE1 的共表达基因主要与染色体分离、DNA 复制和细胞周期检查点有关。蛋白质-蛋白质相互作用分析表明,RAE1 与 NUP205、NUP155、NUP214、NUP54 和 NXF1 密切相关,这些基因在细胞分裂和有丝分裂检查点中都起着重要作用。
RAE1 可以作为一种与微管相关的潜在诊断和预后生物标志物,也是 HCC 的治疗靶点。