Dissecting novel mechanisms of hepatitis B virus related hepatocellular carcinoma using meta-analysis of public data.
Dissecting novel mechanisms of hepatitis B virus related hepatocellular carcinoma using meta-analysis of public data.
复制标题
使用公共数据的荟萃分析剖析乙型肝炎病毒相关肝细胞癌的新机制。
DOI：
10.4251/wjgo.v14.i9.1856
复制
发表时间：
2022-09-15
影响因子：
3
通讯作者：
Mumtaz K
中科院分区：
文献类型：
--
作者：
Aljabban J;Rohr M;Syed S;Cohen E;Hashi N;Syed S;Khorfan K;Aljabban H;Borkowski V;Segal M;Mukhtar M;Mohammed M;Boateng E;Nemer M;Panahiazar M;Hadley D;Jalil S;Mumtaz K
B型肝炎病毒（HBV）是肝细胞癌（HCC）的一种病因。有趣的是，这个过程不一定是通过肝硬化介导的，事实上可能涉及致癌过程。先前的研究表明，特定的致癌基因表达途径受到病毒调节蛋白的影响。因此，识别这些基因和相关通路可以突出HCC转化的预测因素，并对早期诊断和治疗具有意义。阐明HBV在HCC中的致癌作用并确定潜在的治疗靶点。我们利用我们的搜索，标记，分析，资源平台进行荟萃分析的公共数据从国家生物技术信息中心的基因表达综合。我们进行了荟萃分析，包括155个肿瘤样本与185个相邻的非肿瘤样本进行比较，并使用独创性途径分析分析结果。我们的分析显示，肝脏X受体/类维生素A X受体（RXR）激活和法尼醇X受体/RXR激活是其中最重要的经典途径。已鉴定的上游调控因子包括Ras家族基因rab-like蛋白6（RABL 6）。RABL 6在肿瘤发生中的作用开始显现，但其在HBV相关HCC中的具体作用仍不明确。我们的因果分析表明RABL 6通过促进细胞分裂、表观遗传调控和Akt信号转导相关基因介导HBV相关HCC的发病机制。我们进行了生存分析，证实了RABL 6表达越高，死亡率越高。此外，同源框A10（HOXA 10）是一个顶级的上游调控因子，并在我们的分析中强烈上调。HOXA 10最近已被证明有助于体外HCC发病机制。我们的因果分析表明，在体内的作用，通过下调肿瘤抑制因子和其他机制。本荟萃分析描述了RABL 6和HOXA 10在HBV相关HCC发病机制中的可能作用。RABL 6和HOXA 10代表了潜在的治疗靶点，需要进一步研究。
Hepatitis B virus (HBV) is a cause of hepatocellular carcinoma (HCC). Interestingly, this process is not necessarily mediated through cirrhosis and may in fact involve oncogenic processes. Prior studies have suggested specific oncogenic gene expression pathways were affected by viral regulatory proteins. Thus, identifying these genes and associated pathways could highlight predictive factors for HCC transformation and has implications in early diagnosis and treatment. To elucidate HBV oncogenesis in HCC and identify potential therapeutic targets. We employed our Search, Tag, Analyze, Resource platform to conduct a meta-analysis of public data from National Center for Biotechnology Information’s Gene Expression Omnibus. We performed meta-analysis consisting of 155 tumor samples compared against 185 adjacent non-tumor samples and analyzed results with ingenuity pathway analysis. Our analysis revealed liver X receptors/retinoid X receptor (RXR) activation and farnesoid X receptor/RXR activation as top canonical pathways amongst others. Top upstream regulators identified included the Ras family gene rab-like protein 6 (RABL6). The role of RABL6 in oncogenesis is beginning to unfold but its specific role in HBV-related HCC remains undefined. Our causal analysis suggests RABL6 mediates pathogenesis of HBV-related HCC through promotion of genes related to cell division, epigenetic regulation, and Akt signaling. We conducted survival analysis that demonstrated increased mortality with higher RABL6 expression. Additionally, homeobox A10 (HOXA10) was a top upstream regulator and was strongly upregulated in our analysis. HOXA10 has recently been demonstrated to contribute to HCC pathogenesis in vitro. Our causal analysis suggests an in vivo role through downregulation of tumor suppressors and other mechanisms. This meta-analysis describes possible roles of RABL6 and HOXA10 in the pathogenesis of HBV-related HCC. RABL6 and HOXA10 represent potential therapeutic targets and warrant further investigation.
登录
查看更多内容
影响因子：
64.5
作者：
CHEN, LP;ASHE, S;LINSLEY, PS
通讯作者：
LINSLEY, PS
DOI：
10.1073/pnas.090102397
发表时间：
2000-05-09
影响因子：
11.1
作者：
Gaudet, S;Branton, D;Lue, RA
通讯作者：
Lue, RA
影响因子：
5.7
作者：
Deng, Ying-Bing;Nagae, Genta;Kaneda, Atsushi
通讯作者：
Kaneda, Atsushi
微阵列数据的综合分析以揭示肝细胞癌发病机理中的调节模式。
影响因子：
3.4
作者：
Chen J;Qian Z;Li F;Li J;Lu Y
通讯作者：
Lu Y
影响因子：
5.2
作者：
Hishida, Mitsuhiro;Nomoto, Shuji;Kodera, Yasuhiro
通讯作者：
Kodera, Yasuhiro