合并肺间质病变或恶性肿瘤皮肌炎患者的外周血差异基因表达分析

Differentially expressed genes in peripheral blood of patients with dermatomyositis complicated by interstitial lung disease or malignant tumors

目的研究合并肺间质病变或恶性肿瘤的皮肌炎/临床无肌病性皮肌炎(DM/CADM)患者的差异表达基因及相关信号通路。方法2017年1月至2018年1月于上海交通大学医学院附属瑞金医院皮肤科确诊的DM/CADM患者27例,按照合并症状分为3组,即合并肺间质病变组10例,合并恶性肿瘤组8例,无肺间质病变和恶性肿瘤组9例。同时收集7例健康对照。采用高通量RNA测序技术筛选上述4组受试者外周血中差异表达基因,进行基因本体论(GO)分析以及京都基因与基因组百科全书(KEGG)通路富集分析。结果与健康对照相比,DM/CADM患者4820条基因表达上调,137条基因表达下调;GO分析获得显著富集条目49个,其中37个(75.5%)与生物过程相关;KEGG分析差异基因富集于感染、肿瘤以及免疫相关通路。与无肺间质病变和恶性肿瘤组相比,合并肺间质病变组272条基因表达上调,158条基因下调;GO分析获得显著富集条目157个,其中114个(72.6%)与生物过程相关;KEGG分析差异基因富集于细菌感染和自身免疫/炎症通路。合并恶性肿瘤组398条基因表达上调,68条基因表达下调;GO分析获得显著富集条目117个,其中94个(80.3%)与生物过程相关;KEGG分析差异基因富集于糖基化、代谢以及肿瘤相关信号通路。结论DM/CADM患者与健康对照组间、合并肺间质病变或恶性肿瘤的DM/CADM组与无合并症患者组间转录组基因及通路存在差异,细菌感染、细胞因子/趋化因子通路在合并ILD的DM/CADM患者中显著富集,而糖基化、蛋白代谢以及抗原提呈和自然杀伤细胞的细胞毒作用在合并恶性肿瘤的DM/CADM患者中显著富集。

Objective To investigate differentially expressed genes and related signaling pathways in patients with dermatomyositis/clinical amyopathic dermatomyositis(DM/CADM)complicated by interstitial lung disease or malignant tumors.Methods From January 2017 to January 2018,27 DM/CADM patients were enrolled from Department of Dermatology,Ruijin Hospital,Shanghai Jiao Tong University School of Medicine,and divided into 3 groups according to the complications:10 with interstitial lung disease,8 with malignant tumors,and 9 without interstitial lung disease or malignant tumors.Meanwhile,7 healthy controls were enrolled into this study.High-throughput RNA sequencing was performed to screen differentially expressed genes in peripheral blood in the above 4 groups.Then,these genes were subjected to gene ontology(GO)analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis.Results Compared with the healthy controls,4820 up-regulated genes and 137 down-regulated genes were identified in DM/CADM patients;GO analysis revealed 49 significantly enriched items in the DM/CADM patients,37(75.5%)of which were associated with biological processes;KEGG analysis showed that differentially expressed genes were mainly enriched in infection-,tumor-and immune-related pathways in DM/CADM patients.Compared with the patients without interstitial lung disease or malignant tumors,272 up-regulated genes and 158 down-regulated genes were identified in the patients with interstitial lung disease;GO analysis revealed 157 significantly enriched items,114(72.6%)of which were associated with biological processes;KEGG analysis showed that differentially expressed genes were mainly enriched in bacterial infection-and autoimmune/inflammatory-related pathways in the patients with interstitial lung disease.Compared with the patients without interstitial lung disease or malignant tumors,398 up-regulated genes and 68 down-regulated genes were identified in the patients with malignant tumors;GO analysis revealed 117 significantly enriched items,94(80.3%)of which were associated with biological processes;KEGG analysis showed that differentially expressed genes were mainly enriched in glycosylation-,metabolism-and tumor-related signaling pathways in the patients with malignant tumors.Conclusions Differences existed in transcriptomes and pathways between the DM/CADM patients and healthy controls,as well as between the patients with interstitial lung disease or malignant tumors and patients without these complications.Bacterial infection-and cytokine/chemokine-related pathways were significantly enriched in the patients with DM/CADM complicated by interstitial lung disease,while those pathways related to glycosylation,protein metabolism,angtigen presentation and cytotoxic effects of natural killer cells were significantly enriched in the patients with DM/CADM complicated by malignant tumors.