Identification of Potential Genes in Pathogenesis and Diagnostic Value Analysis of Partial Androgen Insensitivity Syndrome Using Bioinformatics Analysis.
Identification of Potential Genes in Pathogenesis and Diagnostic Value Analysis of Partial Androgen Insensitivity Syndrome Using Bioinformatics Analysis.
复制标题
利用生物信息学分析鉴定部分雄激素不敏感综合征发病机制的潜在基因及诊断价值
DOI：
10.3389/fendo.2021.731107
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发表时间：
2021
影响因子：
5.2
通讯作者：
Qiao J
中科院分区：
文献类型：
--
作者：
Peng Y;Zhu H;Han B;Xu Y;Liu X;Song H;Qiao J
背景雄激素不敏感综合征（Androgen insensitivity syndrome，AIS）是一种罕见的X连锁遗传病，是导致46，XY性发育障碍的原因之一。由于AIS的临床表型重叠，其诊断的不直接性和性别分配的困境仍然是该病的一个困扰。方法分离部分AIS（PAIS）患者和健康对照者的外周血单个核细胞（PBMC），采用RNA-seq技术检测其转录组变异。然后，进行组织特异性基因表达、功能富集和蛋白质-蛋白质相互作用（PPI）网络分析;并确定关键模块。最后，通过定量实时PCR（qRT-PCR）验证感兴趣的差异表达基因（DEG）的RNA表达。结果在我们的数据集中，共捕获了725个DEG，具有功能丰富的生殖和免疫相关途径和基因本体（GO）功能。最高度特异性的系统集中在血液/免疫和生殖/内分泌系统。通过PPI网络的关键基因簇和组织特异性基因表达的人工筛选，我们最终筛选出CCR 1、PPBP、PF 4、CLU、KMT 2D、GP 6和CCL 4。这些基因为AIS在免疫系统或代谢中的发病机制提供了新的见解，并为临床筛选提供了可能的分子标记。qRT-PCR结果显示PAIS患者和健康对照之间相关基因的表达水平具有一致的趋势。结论本研究揭示了AIS发病和进展的分子机制，为AIS的诊断和进一步研究提供了潜在的靶点。
Background Androgen insensitivity syndrome (AIS) is a rare X-linked genetic disease and one of the causes of 46,XY disorder of sexual development. The unstraightforward diagnosis of AIS and the gender assignment dilemma still make a plague for this disorder due to the overlapping clinical phenotypes. Methods Peripheral blood mononuclear cells (PBMCs) of partial AIS (PAIS) patients and healthy controls were separated, and RNA-seq was performed to investigate transcriptome variance. Then, tissue-specific gene expression, functional enrichment, and protein–protein interaction (PPI) network analyses were performed; and the key modules were identified. Finally, the RNA expression of differentially expressed genes (DEGs) of interest was validated by quantitative real-time PCR (qRT-PCR). Results In our dataset, a total of 725 DEGs were captured, with functionally enriched reproduction and immune-related pathways and Gene Ontology (GO) functions. The most highly specific systems centered on hematologic/immune and reproductive/endocrine systems. We finally filtered out CCR1, PPBP, PF4, CLU, KMT2D, GP6, and SPARC by the key gene clusters of the PPI network and manual screening of tissue-specific gene expression. These genes provide novel insight into the pathogenesis of AIS in the immune system or metabolism and bring forward possible molecular markers for clinical screening. The qRT-PCR results showed a consistent trend in the expression levels of related genes between PAIS patients and healthy controls. Conclusion The present study sheds light on the molecular mechanisms underlying the pathogenesis and progression of AIS, providing potential targets for diagnosis and future investigation.
影响因子：
4.4
作者：
Holterhus PM;Deppe U;Werner R;Richter-Unruh A;Bebermeier JH;Wünsch L;Krege S;Schweikert HU;Demeter J;Riepe F;Hiort O;Brooks JD
通讯作者：
Brooks JD
影响因子：
12.3
作者：
Holterhus PM;Hiort O;Demeter J;Brown PO;Brooks JD
通讯作者：
Brooks JD