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Involvement of discoidin domain 1 receptor in recurrence of hepatocellular carcinoma by genome-wide analysis

盘状结构域 肝细胞癌 血液学 地址1 内科学 癌症研究 基因组 受体 医学 肿瘤科 生物 遗传学 基因 受体酪氨酸激酶
作者
Zhixiang Jian,Jian Sun,Wei Chen,Haosheng Jin,Jianghua Zheng,Yi‐Long Wu
出处
期刊:Medical Oncology [Springer Nature]
卷期号:29 (5): 3077-3082 被引量:23
标识
DOI:10.1007/s12032-012-0277-x
摘要

Hepatocellular carcinoma (HCC) is highly invasive with a high frequency of recurrence following surgery and poor prognosis. The underlying molecular mechanisms for HCC recurrence are not well understood. Here, we used microarray technology for genome-wide analysis to identify genes who may be involved in tumor recurrence. cDNA from HCC tumor tissues of patients with early recurrence (ER; n = 10) and patients whose HCC had not recurred ≥ 2 years postsurgery (nER; n = 10) was hybridized to the Affymetrix Human Geome U133 plus 2.0 whole-genome microarray. Gene clusters were identified and used for hierarchial clustering and principal component analysis. Genes with more than twofold change in expression between ER and nER groups were further analyzed. Expression levels of a subset of genes were validated using RT-PCR and immunohistochemistry. A total of 1,646 genes had significantly different expression between the ER and nER groups (P < 0.05) with 61 and 49 genes in the ER upregulated and downregulated for more than twofold in comparison with the nER group, respectively. The cellular functions of differentially expressed genes included cell adhesion, motility, cytoskeleton, transcription, metabolism, signal transduction, and apoptosis. The discoidin domain receptor 1 (DDR1) mRNA expression was significantly higher in the ER (3.36 ± 0.39) compared with the nER group (3.01 ± 0.49; P = 0.020). A greater proportion of liver tissue samples from ER versus nER patients had DDR1 protein expression (80.0 vs. 40.0 %, P = 0.022). Using microarray technology, we identified a number of genes whose expression differed between patients with recurrent HCC compared to those without. DD1 mRNA and protein levels were higher in patients with recurrent HCC, suggesting this gene maybe involved in tumor invasion and metastasis.
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