Oncotarget

Research Papers:

Tumor repressor gene chondroadherin oppose migration and proliferation in hepatocellular carcinoma and predicts a good survival

Xiaorong Deng _, Weiwei Wei, Niangen Huang, Yumeng Shi, Mingwen Huang, Yehong Yan, Dongjian Li, Jilin Yi and Xinbao Wang

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Oncotarget. 2017; 8:60270-60279. https://doi.org/10.18632/oncotarget.19811

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Abstract

Xiaorong Deng1,*, Weiwei Wei2,*, Niangen Huang3,*, Yumeng Shi4,*, Mingwen Huang5, Yehong Yan6, Dongjian Li2,*, Jilin Yi2 and Xinbao Wang7

1Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, P.R. China

2Department of General Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, P.R. China

3Digestive Endoscopy Center, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, P.R. China

4School of Basic Medical Sciences, Shandong University, Jinan City, Shandong Province, P.R. China

5Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, P.R. China

6Department of Hepatobiliary Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, P.R. China

7Department of Hepatopancreatobiliary Surgery, Zhejiang Cancer Hospital, Hangzhou, P.R. China

*These authors contributed equally to this work

Correspondence to:

Xiaorong Deng, email: [email protected]

Keywords: CHAD, prognosis, migration, hepatocellular carcinoma, proliferation

Received: June 19, 2017     Accepted: July 25, 2017     Published: August 02, 2017

ABSTRACT

The molecular that used as prognosis and potential therapy target is urgently needed in hepatocellular carcinoma (HCC). In current work, we found the expression of CHAD (chondroadherin) was significantly reduced in hepatocellular carcinoma compared to the normal tissue, on both mRNA and protein levels, in three independent datasets. Survival analysis was implemented on these datasets, and low expression of CHAD was found to be significantly associated with poor survival. Furthermore, metastasis-averse HCC and metastasis-incline HCC group comparison, and protein abundance evaluation of normal-tumor-portal vein tumor thrombus pairs indicate that metastatic tendentiousness is reduced along with CHAD abundance. Correlation analysis was also carried out and CHAD was shown to be significantly associated with differentiation and metastasis. Multivariable cox regression analysis showed that CHAD expression is more important for prognosis, compared to the other clinical indicators. To facilitate the utilization of CHAD clinically, a nomogram was plotted to estimate the three-year survival rate. Functional assays testing the migration and proliferation ability following knock down of CHAD in two cell lines, SMMC7721 and HCCLM3, were performed and discovered that reduction of CHAD level significantly enhance both proliferation and migration in both cell lines. Gene Set Enrichment Analysis (GSEA) comparing the CHAD-low and CHAD-high group showed that KEGG signaling pathways including “focal adhesion”, “ECM receptor interaction”, and “regulation of actin cytoskeleton” were significantly enriched. In conclusion, as a potential prognostic biomarker, tumor suppressor gene CHAD represses migration and proliferation of hepatocellular carcinoma cells, probability via mediating cell-cell adhesion.


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