Dataset Information

Low PLCE1 levels are correlated with poor prognosis in hepatocellular carcinoma.

ABSTRACT:

Background

Previous reports show that phospholipase C epsilon-1 (PLCE1) expression is positively correlated with esophageal squamous cell carcinoma and gastric cardia adenocarcinomas; however, the expression of PLCE1 in hepatocellular carcinoma (HCC) and its correlation with clinical outcome still remain unclear. The aim of this study was to explore the expression of PLCE1 in HCC tissue and to determine whether PLCE1 was a prognostic factor for HCC patients.

Materials and methods

PLCE1 levels in 20 paired HCC tissues and corresponding paracarcinomatous tissues was investigated by quantitative real-time polymerase chain reaction and Western blot assays. In addition, protein levels of PLCE1 in one normal liver epithelial cell and four HCC cell lines were examined using Western blot assay. Moreover, immunohistochemistry was applied to determine the expression of PLCE1 in HCC and corresponding surrounding tissues from 90 patients. Statistical analyses were used to examine the association between PLCE1 levels and clinicopathological features.

Results

We found that the expression of PLCE1 in tumor tissues was significantly lower than those in paracarcinomatous tissues at both mRNA and protein levels (P<0.05). We also determined that PLCE1 protein expression levels were lower in HCC cell lines than normal liver epithelial cells (P<0.05). Notably, immunohistochemical assay showed that PLCE1 expression was significantly low in HCC tissues compared with the adjacent normal liver tissues (40% vs 18.9%; P<0.05). Besides, PLCE1 levels were negatively correlated with tumor capsulae, vascular invasion, Edmondson grade, alpha-fetoprotein, and tumor-node-metastasis stage (P<0.05). Univariate analysis revealed that lower level expression of PLCE1 was significantly associated with poorer overall survival (OS) rate (P<0.001) and disease-free survival rate (P<0.001). Multivariate analysis revealed that low PLCE1 level was an independent poor prognostic factor of OS and recurrence-free survival (P<0.001 and P=0.003, respectively).

Conclusion

In brief, our results revealed that decreased PLCE1 expression was associated with tumor progression in HCC and may function as a promising biomarker for HCC prognosis.

SUBMITTER: Cheng Y

PROVIDER: S-EPMC5182043 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Publications

Low PLCE1 levels are correlated with poor prognosis in hepatocellular carcinoma.

Cheng Ya Y Xing Song-Ge SG Jia Wei-Dong WD Huang Mei M Bian Na-Na NN

OncoTargets and therapy 20161219

<h4>Background</h4>Previous reports show that phospholipase C epsilon-1 (PLCE1) expression is positively correlated with esophageal squamous cell carcinoma and gastric cardia adenocarcinomas; however, the expression of PLCE1 in hepatocellular carcinoma (HCC) and its correlation with clinical outcome still remain unclear. The aim of this study was to explore the expression of PLCE1 in HCC tissue and to determine whether PLCE1 was a prognostic factor for HCC patients.<h ...[more]

PMID: 28031722

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Project description:Background - Hepatocellular carcinomas (HCCs) are heterogeneous tumors with respect to etiology, cell of origin and biology. The course of the disease is unpredictable and is in part dependent on the tumor microenvironment. One of the microenvironmental factors is hypoxia, which is known to promote aggressiveness in other malignant tumors. We hypothesized that certain regions in HCC exist with chronic hypoxia and a characteristic gene expression pattern. Moreover, during the development of HCC there is an important contribution of this chronic hypoxia on prognosis via this gene expression. Until now, most research has been performed in acute hypoxic models (< 24 hours). Methods – Human hepatoblastoma cells HepG2 were cultured in either normoxic (20% O2) or hypoxic (2% O2) conditions for 72 hrs, the time it takes to adapt to chronic hypoxia. After 3 days the cells were harvested and analyzed by microarray technology. The highly significant differentially expressed genes were selected and used to assess the clinical value of our in vitro chronic hypoxia gene signature in four published patient studies. Three of these independent microarray studies on HCC patients were used as training sets to determine a minimal prognostic gene set and one study was used for validation. Gene expression analysis and correlation with clinical outcome was assessed with the bioinfomatic method of Goeman et al (). Results – In the HepG2 cells, 3592 genes were differentially expressed in cells cultured at 2% oxygen for 72 hrs. Out of these, 265 showed a high significant change (2-fold change and p=0.0001). The level of gene expression after 72 hrs was different from the acute hypoxic response (during the first 24 hours) and represented chronicity. Using computational methods we identified 7 out of the 265 highly significant genes that showed correlation with prognosis in all three different training sets and this was independently validated in a 4th dataset. With our approach we could include the largest number of HCC patients in one single study. Conclusion – We identified a 7-gene signature, which is associated with chronic hypoxia and predicts prognosis in patients with HCC. In the future this signature could be used as a diagnostic tool. In addition, chronic hypoxia gene expression information can be used in the search for new therapeutic targets. Two conditions were compared and each sample has a biological replicate. Samples are hybridized in dye-swap, resulting in 4 hybridizations.

Dataset Information

Low PLCE1 levels are correlated with poor prognosis in hepatocellular carcinoma.

Background

Materials and methods

Results

Conclusion

Publications

Low <i>PLCE1</i> levels are correlated with poor prognosis in hepatocellular carcinoma.

Similar Datasets

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