Department of General Surgery, The Affiliated Changzhou No. 2 People's Hospital of Nanjing Medical University, Changzhou, Jiangsu, China.
Nanjing Medical University, Nanjing, Jiangsu, China.
J Cell Mol Med. 2021 Dec;25(24):11097-11112. doi: 10.1111/jcmm.17032. Epub 2021 Nov 5.
The cell division cycle associated 8 (CDCA8) is a crucial component of the chromosome passenger complex (CPC). It has been implicated in the regulation of cell dynamic localization during mitosis. However, its role in hepatocellular carcinoma (HCC) is not clearly known. In this study, data of 374 patients with HCC were retrieved from the Cancer Genome Atlas (TCGA) database. Pan analysis of Gene Expression Profiling Interactive Analysis (GEPIA) database was performed to profile the mRNA expression of CDCA8 in HCC. Then, the Kaplan-Meier plotter database was analysed to determine the prognostic value of CDCA8 in HCC. In addition, samples of tumour and adjacent normal tissues were collected from 88 HCC patients to perform immunohistochemistry (IHC), reverse transcription-quantitative polymerase chain reaction (qRT-PCR) and Western blotting. The results obtained from bioinformatic analyses were validated through CCK-8 assay, EdU assay, colony formation assay, cell cycle assays and Western blotting experiments. Analysis of the Kaplan-Meier plotter database showed that high expression of CDCA8 may lead to poor overall survival (OS, p = 4.06e-05) in patients with HCC. For the 88 patients with HCC, we found that stages and grades appeared to be strongly linked with CDCA8 expression. Furthermore, the high expression of CDCA8 was found to be correlated with poor OS (p = 0.0054) and progression-free survival (PFS, p = 0.0009). In vitro experiments revealed that inhibition of CDCA8 slowed cell proliferation and blocked the cell cycle at the G0/G1 phase. In vivo experiments demonstrated that inhibition of CDCA8 inhibited tumour growth. Finally, blockade of CDCA8 reduced the expression levels of cyclin A2, cyclin D1, CDK4, CDK6, Ki67 and PCNA. And, there is an interaction between CDCA8 and E2F1. In conclusion, this research demonstrates that CDCA8 may serve as a biomarker for early diagnosis and prognosis prediction of HCC patients. In addition, CDCA8 could be an effective therapeutic target in HCC.
细胞分裂周期相关蛋白 8（CDCA8）是染色体乘客复合物（CPC）的关键组成部分。它已被牵连到有丝分裂过程中细胞动态定位的调节。然而，它在肝细胞癌（HCC）中的作用尚不清楚。本研究从癌症基因组图谱（TCGA）数据库中检索了 374 名 HCC 患者的数据。通过基因表达谱交互式分析（GEPIA）数据库进行泛分析，以分析 HCC 中 CDCA8 的 mRNA 表达。然后，分析 Kaplan-Meier 绘谱器数据库以确定 CDCA8 在 HCC 中的预后价值。此外，从 88 名 HCC 患者中收集肿瘤和相邻正常组织样本，进行免疫组织化学（IHC）、逆转录定量聚合酶链反应（qRT-PCR）和 Western blot 分析。通过 CCK-8 测定、EdU 测定、集落形成测定、细胞周期测定和 Western blot 实验验证生物信息学分析的结果。Kaplan-Meier 绘谱器数据库分析显示，CDCA8 高表达可能导致 HCC 患者总生存期（OS，p=4.06e-05）较差。对于 88 名 HCC 患者，我们发现分期和分级似乎与 CDCA8 表达密切相关。此外，CDCA8 高表达与不良 OS（p=0.0054）和无进展生存期（PFS，p=0.0009）相关。体外实验表明，抑制 CDCA8 可减缓细胞增殖并阻断 G0/G1 期细胞周期。体内实验表明，抑制 CDCA8 可抑制肿瘤生长。最后，阻断 CDCA8 降低了细胞周期蛋白 A2、细胞周期蛋白 D1、CDK4、CDK6、Ki67 和 PCNA 的表达水平。并且，CDCA8 与 E2F1 之间存在相互作用。总之，这项研究表明 CDCA8 可作为 HCC 患者早期诊断和预后预测的生物标志物。此外，CDCA8 可能是 HCC 的有效治疗靶点。
