Transcriptome comparison of isotretinoin-effective and isotretinoin-ineffective severe acne vulgaris patients
Transcriptome comparison of isotretinoin-effective and isotretinoin-ineffective severe acne vulgaris patients
复制标题
异维A酸有效和异维A酸无效的重度寻常痤疮患者的转录组比较
DOI：
10.1111/jocd.13898
复制
发表时间：
2020-12-22
影响因子：
2.3
通讯作者：
Zheng, Yue
中科院分区：
文献类型：
--
作者：
Jiang, Yuchen;Zhang, Jie;Zheng, Yue
背景口服异维甲酸是治疗严重结节性痤疮的一线药物。然而，患者口服异维甲酸无效或效果不佳仍是临床难题，其分子遗传机制尚不清楚。目的比较异维a酸有效和无效的重度寻常痤疮患者的转录组谱，分析其潜在的生理作用，以更好地了解异维a酸疗效差异的机制。方法采集43例重度痤疮患者治疗前外周血。在异维a酸治疗8周后，选择对异维a酸治疗有效和无效的患者，并对其预处理外周血进行分析。采用高通量测序检测基因表达谱。利用Gene Ontology和KEGG进行功能标注和通路富集分析。结果10例痤疮患者（男3例，女7例，年龄31±9.2岁）口服异维甲酸有效，10例痤疮患者（男4例，女6例，年龄28±7.7岁）无效。比较异维a酸有效和无效患者的基因谱，发现2779个差异表达基因：2723个表达上调，56个表达下调。差异表达基因富集于RNA降解途径、自噬途径、蛋白泛素化途径、内质网蛋白加工途径、t细胞受体信号途径、剪接体途径、mRNA监视途径、细胞周期途径、长时程增强途径和FoxO信号途径。结论转录组表达差异不仅参与了痤疮的发病机制，而且影响异维甲酸的治疗效果。这些发现可能为探索痤疮患者的个体化治疗提供一些证据。
Background Oral isotretinoin is the first-line treatment of severe nodular acne. However, patients presenting ineffective or poor effective to oral isotretinoin are still a clinical problem, and its molecular genetic mechanisms remain unclear.Aims To compare the transcriptome profiles of isotretinoin-effective and isotretinoin-ineffective severe acne vulgaris patients and analyze the potential physiological roles to better understand the mechanisms of isotretinoin efficacy differences.Patients/Methods Peripheral blood of 43 patients with severe acne was collected before treatment. After 8-week isotretinoin, patients presented effective and ineffective to isotretinoin treatment were selected and their pretreatment peripheral blood was analyzed. High-throughput sequencing was used to detect gene expression profiles. Gene Ontology and KEGG were used to perform functional annotation and pathway enrichment analysis.Results Ten acne patients (3 male and 7 female, age 31 +/- 9.2) presented effectiveness by oral isotretinoin and 10 acne patients (4 male and 6 female, age 28 +/- 7.7) presented ineffectiveness were included. Comparison of gene profiles of isotretinoin-effective and isotretinoin-ineffective patients revealed 2779 differentially expressed genes: 2723 upregulated and 56 downregulated. Differentially expressed genes were enriched in RNA degradation pathway, autophagy pathway, protein ubiquitination pathway, protein processing in endoplasmic reticulum pathway, T-cell receptor signaling pathway, spliceosome pathway, mRNA surveillance pathway, cell cycle pathway, long-term potentiation pathway, and FoxO signaling pathway.Conclusion Transcriptome expression differences not only participated in the acne pathogenesis, but also influenced the isotretinoin therapeutic effects. These findings might provide some evidence for exploring individualized therapy for acne patients.