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鉴定内质网应激相关基因和亚型以预测炎症性肠病的风险特征并描绘免疫特征

Identification of endoplasmic reticulum stress-associated genes and subtypes for predicting risk signature and depicting immune features in inflammatory bowel disease.

作者信息

Liu Ziyu, Zeinalzadeh Zahra, Huang Tao, Han Yingying, Peng Lushan, Wang Dan, Zhou Zongjiang, Ousmane Diabate, Wang Junpu

机构信息

Department of Pathology, Xiangya Hospital, Central South University, Changsha City, Hunan Province, China.

Department of Pathology, School of Basic Medicine, Central South University, Changsha City, Hunan Province, China.

出版信息

Heliyon. 2024 Sep 1;10(17):e37053. doi: 10.1016/j.heliyon.2024.e37053. eCollection 2024 Sep 15.

Abstract

Endoplasmic reticulum stress (ERS) becomes a significant factor in inflammatory bowel disease (IBD), like Crohn's disease (CD) and ulcerative colitis (UC). Our research was aimed at identifying molecular markers to enhance our understanding of ERS and inflammation in IBD, recognizing risk factors and high-risk groups at the molecular level, and developing a predictive model on the grounds of based on ERS-associated genes. This research adopted the least absolute shrinkage and selection operator (LASSO) regression and logistic regression to build a predictive model, and categorized IBD patients into high- and low-risk groups, and then identified four gene clusters. Our key findings included a significant increase in drug target gene expression in high-risk groups, notable discrepancies in immune levels, and functions between high-risk and low-risk groups. Notably, the gene emerged as a strong predictor with the highest diagnostic value (area under the curve [AUC] = 0.941). encodes proteins required for antigenic peptide transfer across the endoplasmic reticulum (ER) membrane, and its potential as a diagnostic marker and therapeutic target is reflected by its overexpression in IBD tissues. Our study established a new ERS-associated gene model which could forecast the risk, immunological status, and treatment efficacy of patients with IBD. These findings suggest potential targets for personalized therapy and highlight the significance of ERS in the etiology and therapy of IBD. Future studies should explore the therapeutic potential of targeting and other ERS-related genes for IBD management.

摘要

内质网应激(ERS)成为炎症性肠病(IBD)如克罗恩病(CD)和溃疡性结肠炎(UC)的一个重要因素。我们的研究旨在确定分子标志物,以增强我们对IBD中ERS和炎症的理解,在分子水平上识别风险因素和高危人群,并基于与ERS相关的基因建立一个预测模型。本研究采用最小绝对收缩和选择算子(LASSO)回归和逻辑回归来构建预测模型,将IBD患者分为高风险和低风险组,然后确定了四个基因簇。我们的主要发现包括高风险组中药物靶基因表达显著增加,高风险和低风险组之间免疫水平和功能存在显著差异。值得注意的是,该基因成为具有最高诊断价值的强预测因子(曲线下面积[AUC]=0.941)。它编码抗原肽跨内质网(ER)膜转运所需的蛋白质,其在IBD组织中的过表达反映了其作为诊断标志物和治疗靶点的潜力。我们的研究建立了一个新的与ERS相关的基因模型,该模型可以预测IBD患者的风险、免疫状态和治疗效果。这些发现提示了个性化治疗的潜在靶点,并突出了ERS在IBD病因学和治疗中的重要性。未来的研究应探索靶向该基因和其他与ERS相关基因对IBD治疗的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c0f4/11409092/7f6d5ae6a122/gr1.jpg

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