Integrated bioinformatic analysis reveals YWHAB as a novel diagnostic biomarker for idiopathic pulmonary arterial hypertension
Integrated bioinformatic analysis reveals YWHAB as a novel diagnostic biomarker for idiopathic pulmonary arterial hypertension
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综合生物信息分析揭示 YWHAB 作为特发性肺动脉高压的新型诊断生物标志物
DOI：
10.1002/jcp.27381
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发表时间：
2019
影响因子：
5.6
通讯作者：
Zeng Hesong
中科院分区：
文献类型：
--
作者：
Wang Tao;Zheng Xuan;Li Ruidong;Liu Xintian;Wu Jinhua;Zhong Xiaodan;Zhang Wenjun;Liu Yujian;He Xingwei;Liu Wanjun;Wang Hongjie;Zeng Hesong
特发性肺动脉高压是一种严重威胁人类生命的心血管疾病。然而，具体的诊断生物标记物尚未完全阐明，IPAH的候选调控靶点也尚未确定。本研究的目的是探索IPAH潜在的诊断生物标志物和可能的调控靶点。基于公共微阵列数据集(GSE703)，我们进行了加权基因共表达网络分析，并计算了模块-性状相关性，发现有6个模块与IPAH相关。进一步分析了与IPAH相关性最强的两个模块，并确定了这两个模块中排名前10位的HUB基因。此外，我们通过定量实时聚合酶链式反应(qRT-PCR)在来自我们研究中心的独立样本集中验证了数据。总的来说，qRT-PCR结果与微阵列分析的大部分结果是一致的。有趣的是，YWHAB基因的变化最大，该基因编码一种属于14-3-3蛋白质家族的蛋白质，其成员通过与含磷酸丝氨酸的蛋白质结合来介导信号转导。因此，YWHAB随后被选中进行验证。与基因表达分析一致的是，IPAH患者血浆14-3-3β浓度显著高于健康对照组，且14-3-3β表达与平均肺动脉压呈正相关(R2= 0.8783；p <；0.001)。综上所述，使用加权基因共表达分析，YWHAB被识别和验证与IPAH的进展相关，这可能作为IPAH的生物标记物和/或治疗靶点。
Idiopathic pulmonary arterial hypertension (IPAH) is a severe cardiovascular disease that is a serious threat to human life. However, the specific diagnostic biomarkers have not been fully clarified and candidate regulatory targets for IPAH have not been identified. The aim of this study was to explore the potential diagnostic biomarkers and possible regulatory targets of IPAH. We performed a weighted gene coexpression network analysis and calculated module‐trait correlations based on a public microarray data set (GSE703) and six modules were found to be related to IPAH. Two modules which have the strongest correlation with IPAH were further analyzed and the top 10 hub genes in the two modules were identified. Furthermore, we validated the data by quantitative real‐time polymerase chain reaction (qRT‐PCR) in an independent sample set originated from our study center. Overall, the qRT‐PCR results were consistent with most of the results of the microarray analysis. Intriguingly, the highest change was found forYWHAB, a gene encodes a protein belonging to the 14‐3‐3 family of proteins, members of which mediate signal transduction by binding to phosphoserine‐containing proteins. Thus,YWHABwas subsequently selected for validation. In congruent with the gene expression analysis, plasma 14‐3‐3β concentrations were significantly increased in patients with IPAH compared with healthy controls, and 14‐3‐3β expression was also positively correlated with mean pulmonary artery pressure (R2= 0.8783;p <0.001). Taken together, using weighted gene coexpression analysis,YWHABwas identified and validated in association with IPAH progression, which might serve as a biomarker and/or therapeutic target for IPAH.