Cell division cycle associated 8: A novel diagnostic and prognostic biomarker for hepatocellular carcinoma

Abstract

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.

Bioinformatics analysis and experimental verification of the prognostic and biological significance mediated by fatty acid metabolism related genes for hepatocellular carcinoma

“…GSEA enrichment was performed to further explore potential molecular mechanism of the model, several pathways (e.g., Cell cycle, DNA replication, ECM receptor interaction, and so on) involving the tumorigenesis were enriched in the high-risk group. It is widely recognized that abnormal cell cycle and DNA replication was considered a biomarker of HCC ( 47 , 48 ). GSVA enrichment showed the model genes were significantly enriched in most signaling oncogenic pathways and were positively correlated, suggesting these risk genes play the oncogenic role in HCC.…”

Identification of multi-omics biomarkers and construction of the novel prognostic model for hepatocellular carcinoma

“…CTHRC1 overexpresses in HCC samples, which can promote tumor invasion, proliferation, and motility and predicts poor prognosis 34 , 35 . STC2 and CDCA8 also have been demonstrated to be significantly associated with the cell proliferation, migration, and growth of HCC, and high expression of them leads to poor overall survival 36 – 39 . These findings proved that NEIL3, CTHRC1, STC2, and CDCA8 are prognostic risk factors in HCC, which is in line with our analysis (Fig.…”

Overexpression of CDCA8 Predicts Poor Prognosis and Promotes Tumor Cell Growth in Prostate Cancer

“…Consumption of CDCA8 leads to cell cycle arrest in the G2/M phase, increased DNA damage and apoptosis, and enhanced sensitivity of ovarian cancer cells to cisplatin and olaparib ( 21 ). Through the ROCK signaling pathway, CDCA8 knockdown may inhibit cancer cell proliferation and invasion ( 22 ). However, the importance of CDCA8 in PCa has not been fully elucidated.…”