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Overexpression of RALY promotes migration and predicts poor prognosis in hepatocellular carcinoma.

ABSTRACT: Introduction:RALY plays a critical role in promoting invasiveness and is associated with poor prognosis in different types of cancers. However, the prognostic value of RALY and its precise role in hepatocellular carcinoma (HCC) remain unknown. Materials and methods:We detected the expression of RALY in 127 clinical HCC tissue samples and seven HCC cell lines by immunohistochemical staining and Western blotting. The prognostic value of RALY expression was assessed using the Kaplan-Meier method. The expression and prognostic value of RALY were also studied by bioinformatics analysis of data from the Gene Expression Omnibus and The Cancer Genome Atlas. The biological influence of RALY on HCC cell lines was studied using proliferation, transwell migration, and invasion assays in vitro. Results:The expression of RALY in HCC tissues was significantly higher than that in adjacent normal liver tissues. Abnormally high expression of RALY was associated with tumor size (P=0.031), TNM stage (P=0.026), presurgical serum AFP levels (P=0.025), and vascular invasion (P=0.001). Kaplan-Meier analysis demonstrated that higher expression of RALY correlated with poorer overall survival and disease-free survival in HCC patients. High RALY expression was an independent adverse prognostic factor for overall survival (HR =2.559, 95% CI: 1.710-3.827, P<0.001) and disease-free survival (HR =2.053, 95% CI: 1.384-3.047, P<0.001) in HCC. Moreover, knockdown of RALY expression using a specific shRNA suppressed the proliferation, migration, and invasion capabilities of HCC cells in vitro. Knockdown of RALY expression in HCC cell lines resulted in upregulation of E-cadherin and downregulation of N-cadherin, vimentin, and snail. Conclusion:Taken together, our results indicate that RALY represents a biomarker for the prognosis of patients with HCC and highlight the importance of RALY as an oncogene in HCC.

SUBMITTER: Zhu Z

PROVIDER: S-EPMC6235007 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Overexpression of RALY promotes migration and predicts poor prognosis in hepatocellular carcinoma.

Zhu Zebin Z Zhang Yixi Y Huang Chensong C Tang Yunhua Y Sun Chengjun C Ju Weiqiang W He Xiaoshun X

Cancer management and research 20181109

<h4>Introduction</h4>RALY plays a critical role in promoting invasiveness and is associated with poor prognosis in different types of cancers. However, the prognostic value of RALY and its precise role in hepatocellular carcinoma (HCC) remain unknown.<h4>Materials and methods</h4>We detected the expression of RALY in 127 clinical HCC tissue samples and seven HCC cell lines by immunohistochemical staining and Western blotting. The prognostic value of RALY expression was assessed using the Kaplan- ...[more]

PMID: 30519104

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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.

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Overexpression of RALY promotes migration and predicts poor prognosis in hepatocellular carcinoma.

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Overexpression of RALY promotes migration and predicts poor prognosis in hepatocellular carcinoma.

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