Dataset Information

Allele loss and down-regulation of heparanase gene are associated with the progression and poor prognosis of hepatocellular carcinoma.

ABSTRACT:

Objectives

The role of heparanase (HPSE) gene in cancers including hepatocellular carcinoma (HCC) is currently controversial. This study was aimed at investigating the impact of genetic alteration and expression change of HPSE on the progression and prognosis of HCC.

Methods

The HPSE gene was studied in three different aspects: (1) loss of heterozygosity (LOH) by a custom SNP microarray and DNA copy number by real-time PCR; (2) mRNA level by qRT-PCR; and (3) protein expression by immunohistochemistry. The clinical significances of allele loss and expression change of HPSE were analyzed.

Results

Microarray analysis showed that the average LOH frequency for 10 SNPs located within HPSE gene was 31.6%, three of which were significantly correlated with tumor grade, serum HBV-DNA level, and AFP concentration. In agreement with SNP LOH data, DNA copy number loss of HPSE was observed in 38.74% (43/111) of HCC cases. HPSE mRNA level was notably reduced in 74.1% (83/112) of tumor tissues compared with non-tumor liver tissues, which was significantly associated with DNA copy number loss, increased tumor size, and post-operative metastasis. HPSE protein level was also remarkably reduced in 66.3% (53/80) of tumor tissues, which was correlated with tumor grade. Patients with lower expression level of HPSE mRNA or protein had a significantly lower survival rate than those with higher expression. Cox regression analysis suggested that HPSE protein was an independent predictor of overall survival in HCC patients.

Conclusions

The results in this study demonstrate that genetic alteration and reduction of HPSE expression are associated with tumor progression and poor prognosis of HCCs, suggesting that HPSE behaves like a tumor suppressor gene and is a potential prognostic marker for HCC patients.

SUBMITTER: Huang GL

PROVIDER: S-EPMC3432106 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Allele loss and down-regulation of heparanase gene are associated with the progression and poor prognosis of hepatocellular carcinoma.

Huang Guo-Liang GL Li Bin-Kui BK Zhang Mei-Yin MY Wei Rong-Rong RR Yuan Yun-Fei YF Shi Ming M Chen Xiao-Qian XQ Huang Long L Zhang Hui-Zhong HZ Liu Wanqing W Huang Bi-Jun BJ Li Honghua H Zheng Xiao-Feng XF Luo Xian-Rong XR Wang Hui-Yun HY

PloS one 20120831 8

<h4>Objectives</h4>The role of heparanase (HPSE) gene in cancers including hepatocellular carcinoma (HCC) is currently controversial. This study was aimed at investigating the impact of genetic alteration and expression change of HPSE on the progression and prognosis of HCC.<h4>Methods</h4>The HPSE gene was studied in three different aspects: (1) loss of heterozygosity (LOH) by a custom SNP microarray and DNA copy number by real-time PCR; (2) mRNA level by qRT-PCR; and (3) protein expression by ...[more]

PMID: 22952874

Similar Datasets

Project description:Opioid receptors have become increasingly implicated in cancer progression and long-term patient outcomes. However, the expression and significance of the ?-opioid receptor (KOR) in hepatocellular carcinoma (HCC) remain unclear.In this study, KOR mRNA expression was analysed by real-time quantitative PCR in 64 pairs of HCC tumour tissues and adjacent non-tumour tissues, and KOR protein expression was analysed by immunohistochemistry in 174 HCC patients. We investigated the correlation between KOR expression and clinicopathological parameters to illustrate the potential prognostic significance of KOR expression in HCC.KOR mRNA expression was significantly down-regulated in 79.69% (51 of 64) of the HCC tumour samples, and KOR expression in tumour tissue was significantly lower than that in adjacent non-tumour tissues (P < 0.001). ROC curve analysis showed that KOR mRNA expression yielded AUC of 0.745, for the detection of HCC patients. Low KOR mRNA expression in HCC was correlated with aggressive clinicopathological parameters, such as tumour size (P = 0.015), differentiation grade (P = 0.011), and TNM stage (P = 0.021). Moreover, down-regulation of KOR protein expression in HCC tissues was detected in 174 HCC patients. Similarly, negative KOR protein expression was significantly correlated with aggressive clinicopathological features, such as tumour size (P = 0.002), vascular invasion (P = 0.003), differentiation grade (P = 0.026), and TNM stage (P = 0.030). Furthermore, Kaplan-Meier survival analysis demonstrated that down-regulation of KOR in HCC indicated poor prognosis. KOR deficiency (KORT?<?N) was correlated to a shorter survival rate and an increased recurrence (both P < 0.001). In univariate and multivariate survival analyses, KOR was identified as a promising independent risk factor for both overall survival (OS, both P < 0.001) and recurrence-free survival (RFS, both P < 0.001).Down-regulation of KOR in HCC tumour tissues has a strong association with poor prognosis and KOR might be a potential tumour suppressor.

Dataset Information

Allele loss and down-regulation of heparanase gene are associated with the progression and poor prognosis of hepatocellular carcinoma.

Objectives

Methods

Results

Conclusions

Publications

Allele loss and down-regulation of heparanase gene are associated with the progression and poor prognosis of hepatocellular carcinoma.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets