Network Integration Analysis and Immune Infiltration Analysis Reveal Potential Biomarkers for Primary Open-Angle Glaucoma.
Network Integration Analysis and Immune Infiltration Analysis Reveal Potential Biomarkers for Primary Open-Angle Glaucoma.
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DOI：
10.3389/fcell.2021.793638
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发表时间：
2021
影响因子：
5.5
通讯作者：
Sun H
中科院分区：
文献类型：
--
作者：
Wang L;Yu T;Zhang X;Cai X;Sun H
原发性开角型青光眼(POAG)是一种进行性视神经病变，对视力的损害不可逆转。因此，在生物标志物的辅助下进行早期诊断至关重要。尽管对POAG生物标志物的识别有多种研究，但从基因转录前后的角度系统揭示POAG的转录组失调机制的研究很少。在这里，我们收集了多组POAG房水(AH)组织转录图谱，包括长非编码RNA(LncRNA)、mRNA和mircoRNA(MiRNA)。通过差异表达分析，我们在POAG和非青光眼的AH组织中发现了数千个显著差异表达基因(DEG)。进一步，利用DEGS构建了竞争内源RNA(Cerna)调控网络，并鉴定了1,653个合格的lncRNA-miRNA-mRNA调控单元。基于随机游走算法识别了两个CERNA调控子网，并发现它们参与了多种复杂疾病的调控。在转录前调控水平，构建了转录调控网络，并鉴定了三个转录因子(FOS、ATF4和RELB)来调控多个基因的表达，参与T细胞的调控。此外，我们通过免疫渗透分析揭示了POAG患者AH组织的免疫沙漠状态，发现AL590666.2-hsa−miR−339−5p-UROD轴可作为POAG的生物标志物。总之，调控机制和生物标志物的识别将有助于POAG的个体化诊断和治疗。
Primary open-angle glaucoma (POAG) is a progressive optic neuropathy and its damage to vision is irreversible. Therefore, early diagnosis assisted by biomarkers is essential. Although there were multiple researches on the identification of POAG biomarkers, few studies systematically revealed the transcriptome dysregulation mechanism of POAG from the perspective of pre- and post-transcription of genes. Here, we have collected multiple sets of POAG’s aqueous humor (AH) tissue transcription profiles covering long non-coding RNA (lncRNA), mRNA and mircoRNA (miRNA). Through differential expression analysis, we identified thousands of significant differentially expressed genes (DEGs) between the AH tissue of POAG and non-glaucoma. Further, the DEGs were used to construct a competing endogenous RNA (ceRNA) regulatory network and 1,653 qualified lncRNA-miRNA-mRNA regulatory units were identified. Two ceRNA regulatory subnets were identified based on the random walk algorithm and revealed to be involved in the regulation of multiple complex diseases. At the pre-transcriptional regulation level, a transcriptional regulatory network was constructed and three transcription factors (FOS, ATF4, and RELB) were identified to regulate the expression of multiple genes and participate in the regulation of T cells. Moreover, we revealed the immune desert status of AH tissue for POAG patients based on immune infiltration analysis and identified a specific AL590666.2-hsa−miR−339−5p-UROD axis can be used as a biomarker of POAG. Taken together, the identification of regulatory mechanisms and biomarkers will contribute to the individualized diagnosis and treatment for POAG.
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DOI：
10.1038/nrc.2017.99
发表时间：
2018-01
期刊：
Nature reviews. Cancer
影响因子：
--
作者：
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通讯作者：
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影响因子：
3.5
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影响因子：
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