Dataset Information

Cell division cycle 34 is highly expressed in hepatitis C virus-positive hepatocellular carcinoma with favorable phenotypes.

ABSTRACT: Despite tremendous efforts to develop curative agents, there are few effective drugs for the treatment of hepatocellular carcinoma (HCC). This is predominantly due to the variations in individual HCC cases. As numerous HCC cases have no mutations in known tumor-associated genes, identification of novel genes involved in the development and progression of human cancers is considered to be an urgent issue. In the present study, surgical specimens of HCC were analyzed for the expression patterns of ubiquitin-conjugating enzyme, cell division cycle 34 (CDC34), which is hypomethylated in its promoter region and exhibits elevated expression levels in mouse skin tumors. The results of the current study clearly indicated that the elevated CDC34 expression level in cancerous regions was significantly associated with favorable clinicopathological features, such as reduced alanine aminotransferase (ALT) levels and histological grades. Similarly, a higher T/N ratio, which is the ratio of CDC34 expression in HCCs to that in non-tumorous tissues, was significantly associated with favorable features, such as a lower indocyanin green retention rate after 15 min (ICG15R), reduced ?-fetoprotein and smaller tumor size. These results indicate that the CDC34 expression level in HCC is a marker for predicting the HCC prognosis and that CDC34 acts as a tumor suppressor.

SUBMITTER: Takagi K

PROVIDER: S-EPMC5492648 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature

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Cell division cycle 34 is highly expressed in hepatitis C virus-positive hepatocellular carcinoma with favorable phenotypes.

Takagi Keiko K Takayama Tadatoshi T Midorikawa Yutaka Y Hasegawa Hiromasa H Ochiai Takanaga T Moriguchi Masamichi M Higaki Tokio T Soma Masayoshi M Nagase Hiroki H Fujiwara Kyoko K

Biomedical reports 20170518 1

Despite tremendous efforts to develop curative agents, there are few effective drugs for the treatment of hepatocellular carcinoma (HCC). This is predominantly due to the variations in individual HCC cases. As numerous HCC cases have no mutations in known tumor-associated genes, identification of novel genes involved in the development and progression of human cancers is considered to be an urgent issue. In the present study, surgical specimens of HCC were analyzed for the expression patterns of ...[more]

PMID: 28685058

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Project description: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.

Project description:BackgroundDespite the recent identification of several prognostic gene signatures, the lack of common genes among experimental cohorts has posed a considerable challenge in uncovering the molecular basis underlying hepatocellular carcinoma (HCC) recurrence for application in clinical purposes. To overcome the limitations of individual gene-based analysis, we applied a pathway-based approach for analysis of HCC recurrence.ResultsBy implementing a permutation-based semi-supervised principal component analysis algorithm using the optimal principal component, we selected sixty-four pathways associated with hepatitis B virus (HBV)-positive HCC recurrence (p < 0.01), from our microarray dataset composed of 142 HBV-positive HCCs. In relation to the public HBV- and public hepatitis C virus (HCV)-positive HCC datasets, we detected 46 (71.9%) and 18 (28.1%) common recurrence-associated pathways, respectively. However, overlap of recurrence-associated genes between datasets was rare, further supporting the utility of the pathway-based approach for recurrence analysis between different HCC datasets. Non-supervised clustering of the 64 recurrence-associated pathways facilitated the classification of HCC patients into high- and low-risk subgroups, based on risk of recurrence (p < 0.0001). The pathways identified were additionally successfully applied to discriminate subgroups depending on recurrence risk within the public HCC datasets. Through multivariate analysis, these recurrence-associated pathways were identified as an independent prognostic factor (p < 0.0001) along with tumor number, tumor size and Edmondson's grade. Moreover, the pathway-based approach had a clinical advantage in terms of discriminating the high-risk subgroup (N = 12) among patients (N = 26) with small HCC (<3 cm).ConclusionsUsing pathway-based analysis, we successfully identified the pathways involved in recurrence of HBV-positive HCC that may be effectively used as prognostic markers.

Project description:BackgroundCell division cycle-associated 8 (CDCA8) is involved in numerous signaling networks, and it serves a crucial modulatory function in multiple malignant tumors. However, its significance in prognosis and immune infiltration in hepatocellular carcinoma (HCC) remains unclear.Materials and methodsHerein, we examined the CDCA8 levels in tumor tissues, as well as its associated signaling pathways and correlation with immune infiltration. Additionally, we further clarified the prognostic significance of CDCA8 among HCC patients. HCC patient information was recruited from The Cancer Genome Atlas (TCGA). Using bioinformatics, the following parameters were analyzed among HCC patients: CDCA8 expression, enrichment analysis, immune infiltration, and prognosis analysis. Moreover, we employed in vitro investigations, such as, qRT-PCR, immunohistochemistry (IHC), and cell functional experiments to validate our results.ResultsElevated CDCA8 expression in HCC patients was markedly associated with T stage, pathological status (PS), tumor status (TS), histologic grade (HG), and AFP. Elevated CDCA8 expression HCC patients exhibited reduced overall survival (OS) (p < 0.001), disease-specific survival (DSS) (p < 0.001), and progress free interval (PFI) H(p < 0.001). According to the ROC analysis, the area under the curve (AUC) was 0.997. Multivariate analysis revealed that CDCA8 was a stand-alone prognostic indicator of patient OS (p = 0.009) and DSS (p = 0.006). A nomogram was then generated based on the multivariate analysis, and the C-indexes and calibration chart revealed excellent predictive performance in determining HCC patient outcome. Based on the GSEA analysis, CDCA8 modulated the P53, Notch, PPAR, E2F networks. We observed a direct link between CDCA8 levels and Th2 and T helper cells, and a negative link between CDCA8 levels and dendritic cells (DC), neutrophils, cytotoxic cells, and CD8 T cells. Furthermore, CDCA8 deficiency inhibited liver cancer cell proliferation and invasion.ConclusionIn conclusion, these findings indicate that CDCA8 is a new molecular bioindicator of HCC patient prognosis, and it is an excellent candidate for therapeutic target against HCC.

Dataset Information

Cell division cycle 34 is highly expressed in hepatitis C virus-positive hepatocellular carcinoma with favorable phenotypes.

Publications

Cell division cycle 34 is highly expressed in hepatitis C virus-positive hepatocellular carcinoma with favorable phenotypes.

Similar Datasets

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