基于生物信息学筛选肠易激综合征免疫浸润下的染色质调节因子

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摘要目的：通过生物信息学分析，筛选出肠易激综合征(irritable bowel syndrome，IBS)免疫浸润下的潜在染色质调控因子(chromatin regulators，CRs)，并阐述其与免疫细胞、免疫功能之间的联系。方法：整合CRs文件和IBS基因表达矩阵，进行加权基因共表达分析和差异性分析，取其交集CRs；基于交集CRs，进行蛋白质蛋白质相互作用(proteinprotein interaction，PPI)分析并构建网络图；利用基因表达矩阵进行免疫浸润的提取和量化，分析免疫细胞之间和免疫功能之间的相关性和差异性，并与PPI网络图中的CRs进行相关性分析；构建风险模型，分析与免疫浸润密切相关的CRs的风险概率，从而筛选出潜在的CRs。结果： PPI分析共确定13个IBS中存在相互作用的CRs；免疫细胞中，B细胞与滤泡辅助性T细胞的相关系数值最高，呈正相关(r=0.90)；免疫功能中，检查点与T细胞共抑制的相关系数值最高，呈正相关(r=0.89)；与健康受试者相比，IBS患者树突状细胞、未成熟树突状细胞、Th1细胞和抗原呈递共刺激显著增高(P均＜0.05)；CRs与免疫浸润相关性分析结果显示，SIN3转录调节因子家族成员B（SIN3B）与自然杀伤细胞呈正相关，丝氨酸/精氨酸重复基质蛋白2（SRRM2）与Th1细胞、抗原呈递共刺激呈正相关，而DPY30与辅助性T细胞、Th1细胞呈负相关；风险模型结果显示，SIN3B、SRRM2可能是IBS的独立风险因素。结论： SIN3B、SRRM2为IBS免疫浸润的潜在CRs，其可能通过调控自然杀伤细胞、Th1细胞和抗原呈递共刺激，从而调节IBS的发生发展。

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	彭剑岚
	朱永苹
	林寿宁
	廖冬燕
	姜俊玲
	吴月霞

关键词 ： , 肠易激综合征 83, 179), font-family: ????, font-weight: 700, text-align: -webkit-right, background-color: rgb(212, 226, 255), ')" href="#">">, 免疫浸润 83, 179), font-family: ????, font-weight: 700, text-align: -webkit-right, background-color: rgb(212, 226, 255), ')" href="#">">, 染色质调控因子 83, 179), font-family: ????, font-weight: 700, text-align: -webkit-right, background-color: rgb(212, 226, 255), ')" href="#">">, 生物信息学 83, 179), font-family: ????, font-weight: 700, text-align: -webkit-right, background-color: rgb(212, 226, 255), ')" href="#">">, SIN3B 83, 179), font-family: ????, font-weight: 700, text-align: -webkit-right, background-color: rgb(212, 226, 255), ')" href="#">">, SRRM2

Abstract： Objective： To screen out potential chromatin regulators (CRs) under immune infiltration in irritable bowel syndrome (IBS) by bioinformatics analysis and to evaluate their links with immune cells and immune functions. Methods： The CRs file and IBS gene expression matrix were integrated, and weighted gene coexpression analysis and differential analysis were performed to take the intersection CRs; based on the CRs obtained from the intersection, proteinprotein interaction (PPI) analysis was performed and the network diagram was constructed. Immune infiltration was extracted and quantified using a gene expression matrix to analyze the correlation and variability between immune cells and between immune functions; and the correlation with CRs in the PPI network diagram was analysed. By constructing a risk model, we analyzed the risk probability of CRs closely related to immune infiltration, and thus screened out the potential CRs. Results： PPI analysis identified a total of 13 interacting CRs in IBS. Among immune cells, the correlation ship between B cells and follicular T helper cells was the strongest and positively correlated (r=0.90). In immune function, the correlation ship between checkpoint and T cell coinhibition was the strongest and positively correlated (r=0.89). Compared with healthy subjects, IBS patients showed a significant increase in co-stimulation of dendritic cells, immature dendritic cells, Th1 cells, and antigen presentation (all P<0.05). The correlation analysis between CRs and immune infiltration showed that SIN3 transcription regulator family member B gene (SIN3B) was positively correlated with natural killer cells, serine/arginine repetitive matrix protein 2 (SRRM2) was positively correlated with Th1 cells and antigen--presenting cells co-stimulation, while DPY30 was negatively correlated with helper T cells and Th1 cells. Risk model results showed that SIN3B and SRRM2 may be independent risk factors for IBS. Conclusion： SIN3B and SRRM2 are potential CRs for immune infiltration in IBS, which may regulate the occurrence and development of IBS by regulating natural killer cells, Th1 cells and antigen presentation co-stimulation.

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收稿日期: 2022-10-06

基金资助: 全国名老中医药专家传承工作室建设项目［国中医药人教函(2022)75号］；桂派中医大师培养项目［桂中医药科教发(2022)6号］；广西壮族自治区中医药管理局自筹课题(Z20210250)

通讯作者: 朱永苹(通讯作者)，主任医师，硕士生导师，E-mail： 529090217@qq.com

作者简介: 彭剑岚(1995—)，女，硕士，住院医师，主要从事消化系统疾病的中西医结合诊治研究

引用本文:

彭剑岚，朱永苹，林寿宁，廖冬燕，姜俊玲，吴月霞. 基于生物信息学筛选肠易激综合征免疫浸润下的染色质调节因子[J]. 江苏大学学报:医学版, 2024, 34(02): 166-175. PENG Jianlan, ZHU Yongping, LIN Shouning, LIAO Dongyan, JIANG Junling, WU Yuexia. Screening of potential chromatin regulators under immune infiltration in irritable bowel syndrome based on bioinformatics

. Journal of Jiangsu University(Medicine Edition), 2024, 34(02): 166-175.

链接本文:

http://zzs.ujs.edu.cn/xbyxb/CN/ 或 http://zzs.ujs.edu.cn/xbyxb/CN/Y2024/V34/I02/166

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