Dataset Information

Expression and Prognostic Significance of CDK8 and ?-Catenin in Hepatocellular Carcinoma.

ABSTRACT: BACKGROUND/AIM:Cyclin-dependent kinase 8 (CDK8) is known to play an important role in the early development and progression of various cancers, and the Wnt/?-catenin pathway is also involved in cancer progression. Nevertheless, relatively little is known about the regulatory mechanisms of the ?-catenin pathway in hepatocellular carcinoma (HCC). MATERIALS AND METHODS:The complete clinicopathological features of 122 pairs of HCC and adjacent non-tumor tissues were analyzed and immunohistochemistry was used to detect the aberrant expression of CDK8 and ?-catenin. Overall survival rates (OSRs) were evaluated using the Kaplan-Meier method and Cox multivariate analysis was used to assess the prognostic values. RESULTS:Aberrant expression of nuclear ?-catenin and CDK8 are independent prognostic variables that negatively affect the OSR. The aberrant expression of CDK8 was associated with the dysregulated expression of ?-catenin and correlated with a poor prognosis. CONCLUSION:Inhibition of CDK8 and/or nuclear ?-catenin expression pattern could serve as a promising therapeutic strategy for the treatment of HCC.

SUBMITTER: Han SI

PROVIDER: S-EPMC7279855 | biostudies-literature | 2020 May-Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Expression and Prognostic Significance of CDK8 and β-Catenin in Hepatocellular Carcinoma.

Han Song Iy SI Lim Sung-Chul SC

In vivo (Athens, Greece) 20200501 3

<h4>Background/aim</h4>Cyclin-dependent kinase 8 (CDK8) is known to play an important role in the early development and progression of various cancers, and the Wnt/β-catenin pathway is also involved in cancer progression. Nevertheless, relatively little is known about the regulatory mechanisms of the β-catenin pathway in hepatocellular carcinoma (HCC).<h4>Materials and methods</h4>The complete clinicopathological features of 122 pairs of HCC and adjacent non-tumor tissues were analyzed and immun ...[more]

PMID: 32354935

Similar Datasets

Project description:IntroductionWD repeat domain phosphoinositide-interacting protein 3 (WIPI3) is a member of the WIPI protein family, autophagy marker, that is associated with the malignant progression of various human cancers, but its role in hepatocellular carcinoma (HCC) is still unclear.Materials and methodsFirstly, we collected the mRNA expression of WIPI3 in HCC through the platform of Oncomine, as well as the DNA copy number variations (CNVs), and verified it on human HCC cell line and the GEO database. Then, the subgroups and prognosis of HCC were performed by the UALCAN web tool. The mutation of WIPI3 was analyzed by cBioPortal. The coexpression of WIPI3 in HCC was identified from the LinkedOmics database, and function enrichment analysis was done using the LinkFinder module in LinkedOmics. Coexpression gene network was constructed through the STRING database, and the MCODE plug-in of which was used to build the gene modules; both of them were visualized by the Cytoscape software. Finally, the top modular genes in the same patient cohort were constructed through data mining in The Cancer Genome Atlas (TCGA) liver hepatocellular carcinoma (LIHC) by using the UCSC Xena browser.ResultsThe results indicated that WIPI3 was frequently overexpressed in HCC, which could lead to a poor prognosis through the Kaplan-Meier (KM) analysis. Moreover, there existed mutations of WIPI3 in HCC, and the prognosis of WIPI3-altered group was significantly poor based on KM plotter data. Coexpression analysis showed that the coexpression gene of WIPI3 was associated with cell cycle and spliceosome. Further analysis suggested that WIPI3 and eukaryotic translation initiation factor 4A3 (EIF4A3) coordinately regulated the cancer cell cycle by spliceosome as a result of the strong positive correlation between them.ConclusionIn summary, WIPI3 is constantly overexpressed in HCC tissues, resulting in a poor prognosis; therefore, we can identify it as an effective target for the treatment of HCC.

Project description:BackgroundsHepatocellular Carcinoma (HCC) is one of the most common malignancy of liver and HCC-related morbidity and mortality remains at high level. Researchers had investigated whether and how reduced E-cadherin expression impacted the prognosis of patients with HCC but the results reported by different teams remain inconclusive.MethodsA systematic literature search was performed in all available databases to retrieve eligible studies and identify all relevant data, which could be used to evaluate the correlation between reduced E-cadherin expression and clinicopathological features and prognosis for HCC patients. A fixed or random effects model was used in this meta-analysis to calculate the pooled odds ratios (OR) and weighted mean differences (WMD) with 95% confidence intervals (CI).ResultsTotal 2439 patients in thirty studies matched the selection criteria. Aggregation of the data suggested that reduced E-cadherin expression in HCC patients correlated with poor 1-, 3- and 5-year overall survival. The combined ORs were 0.50 (n = 13 studies, 95% CI: 0.37-0.67, Z = 4.49, P<0.00001), 0.39 (n = 13 studies, 95% CI: 0.28-0.56, Z = 5.12, P<0.00001), 0.40 (n = 11 studies, 95% CI: 0.25-0.64, Z = 3.82, P = 0.0001), respectively. Additionally, the pooled analysis denoted that reduced E-cadherin expression negatively impacts recurrence-free survival (RSF) with no significant heterogeneity. The pooled ORs for 1-, 3- and 5- year RSF affected by down-regulated E-cadherin were 0.73 (n = 6 studies, 95% CI: 0.54-1.00, Z = 1.95, P = 0.05), 0.70 (n = 6 studies, 95% CI: 0.52-0.95, Z = 2.32, P = 0.02), 0.66 (n = 5 studies, 95% CI: 0.48-0.90, Z = 2.64, P = 0.008). And what's more, reduced E-cadherin expression tended to be significantly associated with metastasis (OR = 0.31, 95% CI: 0.16-0.60, Z = 3.50, P = 0.0005), vascular invasion (OR = 0.76, 95% CI: 0.59-0.98, Z = 2.14, P = 0.03), advanced differentiation grade (OR = 0.31, 95% CI: 0.21-0.45, Z = 6.04, P<0.00001) and advanced TMN stage (T3/T4 versus T1/T2) (OR = 0.61,95% CI:0.38-0.98, Z = 2.05, P = 0.04).ConclusionsReduced E-cadherin expression indicates a poor prognosis for patients with HCC, and it may have predictive potential for prognosis of HCC patients.

Project description:BACKGROUND: Similarly to other tumor types, an imbalance between unrestrained cell proliferation and impaired apoptosis appears to be a major unfavorable feature of hepatocellular carcinoma (HCC). The members of IAP family are key regulators of apoptosis, cytokinesis and signal transduction. IAP survival action is antagonized by specific binding of Smac/DIABLO and XAF1. This study aimed to investigate the gene and protein expression pattern of IAP family members and their antagonists in a series of human HCCs and to assess their clinical significance. METHODS: Relative quantification of IAPs and their antagonist genes was assessed by quantitative Real Time RT-PCR (qPCR) in 80 patients who underwent surgical resection for HCC. The expression ratios of XIAP/XAF1 and of XIAP/Smac were also evaluated. Survivin, XIAP and XAF1 protein expression were investigated by immunohistochemistry. Correlations between mRNA levels, protein expression and clinicopathological features were assessed. Follow-up data were available for 69 HCC patients. The overall survival analysis was estimated according to the Kaplan-Meier method. RESULTS: Survivin and Livin/ML-IAP mRNAs were significantly over-expressed in cancer tissues compared to non-neoplastic counterparts. Although Survivin immunoreactivity did not correlate with qPCR data, a significant relation was found between higher Survivin mRNA level and tumor stage, tumor grade and vascular invasion.The mRNA ratio XIAP/XAF1 was significantly higher in HCCs than in cirrhotic tissues. Moreover, high XIAP/XAF1 ratio was an indicator of poor prognosis when overall survival was estimated and elevated XIAP immunoreactivity was significantly associated with shorter survival. CONCLUSION: Our study demonstrates that alterations in the expression of IAP family members, including Survivin and Livin/ML-IAP, are frequent in HCCs. Of interest, we could determine that an imbalance in XIAP/XAF1 mRNA expression levels correlated to overall patient survival, and that high XIAP immunoreactivity was a poor prognostic factor.

Project description:PurposeGamma-glutamyl transpeptidase (GGT) family genes play crucial roles in the formation and progression of several solid tumors. However, the expression patterns and the prognostic significance of GGT members in hepatocellular carcinoma (HCC) remain unknown. This study was designed to determine the expression profiles of GGT family members in HCC and validate the prognostic value of serum GGT protein in patients with HCC.MethodWe comprehensively searched public resources based on the LIHC dataset to determine the expression patterns, prognostic significance, DNA methylation status, immune infiltration, and biological pathways of GGT family genes in HCC. Subsequently, we validated the prognostic value of serum GGT protein in 85 patients with early-stage HCC subjected to curative hepatectomy from the Renmin Hospital of Wuhan University.ResultsExcept for GGT1, other GGT family members (GGT5, GGT6, and GGT7) were found to be differentially expressed in primary HCC samples (N = 371) and normal control tissues (N = 50). Furthermore, a positive relationship was not only observed between GGT1 and GGT5 (Spearman coefficient: 0.24, P = 5.143 × 10-6) but also between GGT5 and GGT6 (Spearman coefficient: 0.38, P = 1.24 × 10-13). The expression of GGT1, GGT5, and GGT7 was correlated with overall survival (OS), and GGT7 was associated with disease-free survival (DFS) in patients with HCC. Negative associations between DNA methylation and expression of mRNA were observed for GGT1 (Spearman coefficient: -0.38, P = 6.24e-14), GGT6 (Spearman coefficient: -0.29, P = 1.23e-8), and GGT7 (Spearman coefficient: -0.34, P=6.7e-11). GGT family genes were well correlated with the infiltration levels of immune cells in HCC, especially CD4+ T cells, macrophages, and dendritic cells. Finally, when validated with clinical data from the Renmin cohort, a high expression of serum GGT protein was identified as a strong prognostic element of unfavorable OS (HR = 3.114, P = 0.025), but not of DFS (HR = 1.198, P = 0.05) in patients with HCC subjected to curative hepatectomy.ConclusionTo our knowledge, this is the first comprehensive analysis of the expression patterns and clinical value of GGT family genes in patients with HCC. Our study laid the foundation for the clinical application of the GGT protein in the survival assessment of patients with HCC.

Dataset Information

Expression and Prognostic Significance of CDK8 and ?-Catenin in Hepatocellular Carcinoma.

Publications

Expression and Prognostic Significance of CDK8 and β-Catenin in Hepatocellular Carcinoma.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets