Association of downregulation of cyclin D1 and of overexpression of cyclin E with p53 mutation, high tumor grade and poor prognosis in hepatocellular carcinoma

Serum levels of the tumor marker CA19-9 have been reported to be elevated in patients with hepatocellular carcinoma (HCC), but its clinicopathologic significance is still unknown. A cohort of 304 patients undergoing surgical resection for HCC and having preoperative CA19-9 data was enrolled in this study. Serum CA19-9 levels were correlated with clinicopathologic factors. Univariate and multivariate analyses were performed to determine the predictors of patient survival. On receiver operating characteristic curve analysis, the cut off value of CA19-9 was determined to be 27 U/mL. One hundred and six patients had preoperative CA19-9 values >27 U/mL. High serum CA19-9 levels did not correlate with patient age, sex, viral status,α-fetoprotein level, tumor size, tumor grade, tumor stage, multiplicity, and vascular invasion. Patients with elevated preoperative CA19-9 levels had lower 10-year survival than those without CA19-9 elevation. Multivariate analysis revealed that CA19-9 level, tumor grade, and tumor size are independent prognostic factors for long-term survival. In conclusion, a preoperative CA19-9 value >27 U/mL is associated with poor prognosis after resection for HCC.

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Expression of cyclin D1, cyclin E, cdk4 and loss of heterozygosity of 8p, 13q, 17p in hepatocellular carcinoma: comparison study of childhood and adult hepatocellular carcinoma

Liver International ◽

10.1034/j.1600-0676.2000.020002173.x ◽

2000 ◽

Vol 20 (2) ◽

pp. 173-178 ◽

Cited By ~ 41

Author(s):

Hanseong Kim ◽

Min Jae Lee ◽

Mi Ran Kim ◽

In Pyung Chung ◽

Yeon Mee Kim ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Cyclin D1 ◽

Loss Of Heterozygosity ◽

Cyclin E ◽

Comparison Study

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Metabolic Pathways Enhancement Confers Poor Prognosis in p53 Exon Mutant Hepatocellular Carcinoma

Cancer Informatics ◽

10.1177/1176935119899913 ◽

2020 ◽

Vol 19 ◽

pp. 117693511989991

Author(s):

Po-Ming Chen ◽

Jian-Rong Li ◽

Chun-Chi Liu ◽

Feng-Yao Tang ◽

En-Pei Isabel Chiang

Keyword(s):

Gene Expression ◽

Hepatocellular Carcinoma ◽

Poor Prognosis ◽

Expression Profiles ◽

Therapeutic Targets ◽

P53 Mutation ◽

Gene Set Enrichment Analysis ◽

Enrichment Score ◽

Rna Seq ◽

P53 Expression

RNA-Sequencing (RNA-Seq), the most commonly used sequencing application tool, is not only a method for measuring gene expression but also an excellent media to detect important structural variants such as single nucleotide variants (SNVs), insertion/deletion (Indels), or fusion transcripts. The Cancer Genome Atlas (TCGA) contains genomic data from a variety of cancer types and also provides the raw data generated by TCGA consortium. p53 is among the top 10 somatic mutations associated with hepatocellular carcinoma (HCC). The aim of the present study was to analyze concordant different gene profiles and the priori defined set of genes based on p53 mutation status in HCC using RNA-Seq data. In the study, expression profile of 11 799 genes on 42 paired tumor and adjacent normal tissues was collected, processed, and further stratified by the mutated versus normal p53 expression. Furthermore, we used a knowledge-based approach Gene Set Enrichment Analysis (GSEA) to compare between normal and p53 mutation gene expression profiles. The statistical significance (nominal P value) of the enrichment score (ES) genes was calculated. The ranked gene list that reflects differential expression between p53 wild-type and mutant genotypes was then mapped to metabolic process by KEGG, an encyclopedia of genes and genomes to assign functional meanings. These approaches enable us to identify pathways and potential target gene/pathways that are highly expressed in p53 mutated HCC. Our analysis revealed 2 genes, the hexokinase 2 ( HK2) and Enolase 1 ( ENO1), were conspicuous of red pixel in the heatmap. To further explore the role of these genes in HCC, the overall survival plots by Kaplan-Meier method were performed for HK2 and ENO1 that revealed high HK2 and ENO1 expression in patients with HCC have poor prognosis. These results suggested that these glycolysis genes are associated with mutated-p53 in HCC that may contribute to poor prognosis. In this proof-of-concept study, we proposed an approach for identifying novel potential therapeutic targets in human HCC with mutated p53. These approaches can take advantage of the massive next-generation sequencing (NGS) data generated worldwide and make more out of it by exploring new potential therapeutic targets.

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