Identification of survival-related predictors in hepatocellular carcinoma through integrated genomic, transcriptomic, and proteomic analyses
Identification of survival-related predictors in hepatocellular carcinoma through integrated genomic, transcriptomic, and proteomic analyses
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DOI：
10.1016/j.biopha.2019.108856
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发表时间：
2019-06-01
影响因子：
7.5
通讯作者：
Bao, Zhijun
中科院分区：
文献类型：
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作者：
Dong, Fangyuan;Yang, Qin;Bao, Zhijun
患者生存时间通常反映肿瘤进展，并代表关键临床参数。在这项研究中，我们的目的是全面描述肝细胞癌（HCC）中肿瘤相关的分子改变。在这项研究中，获得了由癌症基因组图谱（TCGA）分析的HCC样本中的拷贝数变化、基因突变、mRNA表达和反相蛋白阵列数据。然后根据临床结果将肿瘤分为两组，并确定与HCC预后相关的基因组学、转录组学和蛋白质组学特征。我们发现，几个拷贝数扩增和缺失可以区分预后不良的HCC患者与预后较好的患者。突变的DNAH 8表现出更差的肿瘤特异性模式，并与HCC无病生存率降低相关。通过整合RNA测序数据，我们发现预后不良的HCC样本与细胞周期过程的上调一致相关，如染色体分离、DNA复制、胞质分裂等。在蛋白质组水平，7种蛋白质在预后不良的样本中显著富集，包括乙酰化α-微管蛋白、p62-LCK-配体、ARID 1 A、MSH 6、B-Raf、Cyclin B1、PEA15。乙酰化α-微管蛋白在HCC组织中频繁表达，并作为HCC的一个有希望的预后因子。这些改变为制定相关的治疗策略奠定了基础，并提高了我们对HCC发病机制的认识。
Patient survival time generally reflects the tumor progression and represents a key clinical parameter. In this study, we aimed to comprehensively characterize the prognosis-associated molecular alterations in hepatocellular carcinoma (HCC). In this study, copy-number changes, gene mutations, mRNA expression, and reverse phase protein arrays data in HCC samples profiled by The Cancer Genome Atlas (TCGA) were obtained. Tumors were then stratified into two groups based on the clinical outcome and identified genomic, transcriptomic, and proteomic traits associated to HCC prognosis. We found that several copy number amplifications and deletions can discriminate HCC patients with poor prognosis from those with better prognosis. Mutated DNAH8 showed a worse prognosis-specific pattern and correlated with a reduced disease-free survival in HCC. By integrating RNA sequencing data, we found that HCC samples with poor prognosis are consistently associated with the up-regulation of cell cycle process, such as chromosome separation, DNA replication, cytokinesis, and etc. At the proteomic level, seven proteins were significantly enriched in samples with poor prognosis, including acetylated alpha-Tubulin, p62-LCK-ligand, ARID1 A, MSH6, B-Raf, Cyclin B1, and PEA15. Acetylated alpha-Tubulin was frequently expressed in HCC tissues and acted as a promising prognostic factor for HCC. These alterations lay a foundation for developing relevant therapeutic strategies and improve our knowledge of the pathogenesis of HCC.