Comprehensive investigation of p53, p21, nm23, and VEGF expression in hepatitis B virus-related hepatocellular carcinoma overall survival after hepatectomy

Comprehensive investigation of p53, p21, nm23, and VEGF expression in hepatitis B virus-related hepatocellular carcinoma overall survival after hepatectomy
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全面调查p53、p21、nm23和VEGF表达在乙型肝炎病毒相关性肝细胞癌肝切除术后总生存中的影响。

DOI:
10.7150/jca.33766
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发表时间:
2020-01
期刊:
影响因子:
3.9
通讯作者:
Ye X
Ye X
中科院分区:
医学3区
文献类型:
--
作者:
Zhu Guang-Zhi;Liao Xi-Wen;Wang Xiang-Kun;Gong Yi-Zhen;Liu Xiao-Guang;Yu Long;Han Chuang-Ye;Yang Cheng-Kun;Su Hao;Huang Ke-Tuan;Yu Ting-Dong;Huang Jian-Lu;Li Jia;Zeng Zhi-Ming;Qin Wei;Liu Zheng-Qian;Zhou Xin;Liu Jun-Qi;Lu Lei;Han Quan-Fa;Shang Li-Ming;Ye X

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目的:本研究旨在探讨p53、p21、nm 23和VEGF在B型肝炎病毒(HBV)相关性肝癌(HCC)切除术后预后中的免疫组化表达及其作为预后指标的分子机制。研究方法:对419例广西南部地区HBV相关性肝癌患者进行免疫组化检测,以评估这些生物标志物的表达与预后的关系。从GSE 14520获得HBV相关HCC的全基因组表达微阵列数据集。结果如下:在我们的研究中,p53、p21和nm 23在乙型肝炎相关肝细胞癌患者癌组织中的表达不影响2年、5年或总体的临床结局。VEGF高表达患者术后2年总生存率低于低表达患者(校正P=0.040,校正HR = 1.652,95% CI = 1.024-2.665)。GSE 14520队列中VEGF的生存分析也表明VEGF mRNA表达与HBV相关的HCC OS显著相关(校正P=0.035,校正HR =1.651,95% CI =1.035-2.634)。共表达分析提示VEGF可能参与调控细胞增殖、生长和凋亡过程,参与调控Rap 1信号通路、HIF-1信号通路、PPAR信号通路、细胞周期。而GSEA提示VEGF可能参与了HIF和HIF 1A通路的调节,以及TP 53调节通路。结论:我们的研究结果表明,VEGF可能是HBV相关HCC的预后指标,我们还通过全基因组共表达和GSEA方法确定了VEGF的潜在分子机制。
Objective: The goal of our current study is to assess the immunohistochemical of p53, p21, nm23, and VEGF expression in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) prognosis after hepatectomy, as well as the prospective molecular mechanisms of prognostic indicator. Methods: There were 419 HBV-related HCC patients who were from southern China of Guangxi province and were used to evaluate the immunohistochemical expression for these biomarkers in prognosis. A genome-wide expression microarray dataset of HBV-related HCC were obtained from GSE14520. Results: In our study, the expression of p53, p21, and nm23 in cancer tissues of patients with hepatitis B-related hepatocellular carcinoma did not affected the clinical outcome of 2 years, 5 years or overall. Patients with high expression of VEGF had a worse overall survival after 2 years of surgery than patients with low expression (adjusted P=0.040, adjusted HR = 1.652, 95% CI = 1.024-2.665). Survival analysis of VEGF in GSE14520 cohort also demonstrated that VEGF mRNA expression also significantly associated with HBV-related HCC OS (adjusted P=0.035, adjusted HR =1.651, 95% CI =1.035-2.634). The prospective molecular mechanisms by co-expression analysis suggested that VEGF might be correlated to regulation of cell proliferation, cell growth and apoptotic process, Rap1 signaling pathway, HIF-1 signaling pathway, PPAR signaling pathway, cell cycle. Whereas the GSEA suggested that VEGF might involve in the regulation of HIF and HIF1A pathway, and TP53 regulation pathway. Conclusion: Our findings suggested that VEGF might be a prognostic indicator of HBV-related HCC, and we also identified the VEGF prospective molecular mechanisms through the whole genome co-expression and GSEA approaches.
DOI: 10.7150/jca.25221
发表时间: 2018
期刊: Journal of Cancer
影响因子: 3.9
作者:
Liao X;Liu X;Yang C;Wang X;Yu T;Han C;Huang K;Zhu G;Su H;Qin W;Huang R;Yu L;Deng J;Zeng X;Ye X;Peng T
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发表时间: 1991-11
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发表时间: 2010-08-01
影响因子: 3.5
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DOI: 10.1371/journal.pone.0064598
发表时间: 2013
期刊: PloS one
影响因子: 3.7
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