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

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单位: [1]Nanchang Univ, Dept Gastrointestinal Surg, Affiliated Hosp 2, Nanchang, Jiangxi, Peoples R China [2]Huazhong Univ Sci & Technol,Tongji Hosp,Dept Gen Surg,Tongji Med Coll,Wuhan,Hubei,Peoples R China [3]Nanchang Univ, Digest Endoscopy Ctr, Affiliated Hosp 2, Nanchang, Jiangxi, Peoples R China [4]Shandong Univ, Sch Basic Med Sci, Jinan, Shandong, Peoples R China [5]Nanchang Univ, Dept Hepatobiliary Surg, Affiliated Hosp 2, Nanchang, Jiangxi, Peoples R China [6]Nanchang Univ, Dept Hepatobiliary Surg, Affiliated Hosp 1, Nanchang, Jiangxi, Peoples R China [7]Zhejiang Canc Hosp, Dept Hepatopancreatobiliary Surg, Hangzhou, Zhejiang, Peoples R China
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关键词: CHAD prognosis migration hepatocellular carcinoma proliferation

摘要:
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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出版当年[2016]版:
大类 | 1 区 医学
小类 | 2 区 细胞生物学 2 区 肿瘤学
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Q1 CELL BIOLOGY Q1 ONCOLOGY
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第一作者单位: [1]Nanchang Univ, Dept Gastrointestinal Surg, Affiliated Hosp 2, Nanchang, Jiangxi, Peoples R China
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