Identification and Validation of Key Genes Involved in the Coupling of Mitochondria-Associated Endoplasmic Reticulum Membrane in Hemorrhoidal Disease.

IF 2 4区 医学 Q2 MEDICINE, GENERAL & INTERNAL
International Journal of General Medicine Pub Date : 2025-05-31 eCollection Date: 2025-01-01 DOI:10.2147/IJGM.S511281
Lihua Mao, Zhiying Rao, Yanru Wang, Jun Yang, Junmei He, Zhi Zheng, Lanyu Chen
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引用次数: 0

Abstract

Background: Hemorrhoidal disease (HD) is the most prevalent rectal disorder, with various cellular processes influenced by the mitochondria-associated endoplasmic reticulum membrane (MAM). Potential therapeutic mechanisms for HD may be associated with MAM. This study aims to identify key genes linked to MAM in HD and to provide novel therapeutic targets.

Methods: Transcriptome data and MAM-related genes (MAM-RGs) were obtained from the Gene Expression Omnibus (GEO) database and relevant literature. Differential expression analysis and single-sample Gene Set Enrichment Analysis (ssGSEA) scores were initially employed to identify candidate genes. Key genes were further refined using Least Absolute Shrinkage and Selection Operator (LASSO) and Protein-Protein Interaction (PPI) networks. A nomogram based on these key genes was developed and assessed. Additionally, CIBERSORT algorithms were utilized to evaluate immune cell infiltration abundance, differences, and correlations in the samples. Finally, the expression of key genes was validated via reverse transcription-quantitative PCR (RT-qPCR).

Results: Differential expression analysis identified 956 differentially expressed genes (DEGs), and ssGSEA identified 143 differentially expressed MAM-RGs. A total of 50 candidate genes were selected through their intersection. Machine learning identified two key genes, MUC16 and DEFA5. A nomogram with strong predictive capability was constructed. Immune cell analysis revealed two types of differential immune cells-activated dendritic cells and plasma cells-where activated dendritic cells were more highly expressed in the case group, and plasma cells showed a strong positive correlation with DEFA5. Additionally, MUC16 was significantly overexpressed in patients with HD, while DEFA5 exhibited down-regulation compared to controls.

Conclusion: This study identifies MUC16 and DEFA5 as key genes associated with HD and MAM and presents a predictive nomogram with high accuracy. These findings provide novel insights into the mechanisms and potential treatment targets for HD.

痔疮病线粒体相关内质网膜偶联关键基因的鉴定与验证。
背景:痔疮病(HD)是最常见的直肠疾病,各种细胞过程受到线粒体相关内质网膜(MAM)的影响。HD的潜在治疗机制可能与MAM有关。本研究旨在确定HD中与MAM相关的关键基因,并提供新的治疗靶点。方法:从Gene Expression Omnibus (GEO)数据库和相关文献中获取转录组数据和mam相关基因(MAM-RGs)。最初采用差异表达分析和单样本基因集富集分析(ssGSEA)评分来鉴定候选基因。使用最小绝对收缩和选择算子(LASSO)和蛋白质相互作用(PPI)网络进一步细化关键基因。基于这些关键基因,建立并评估了一个nomogram。此外,利用CIBERSORT算法评估样本中免疫细胞浸润的丰度、差异和相关性。最后,通过逆转录定量PCR (RT-qPCR)验证关键基因的表达。结果:差异表达分析鉴定出956个差异表达基因(deg), ssGSEA鉴定出143个差异表达的MAM-RGs。通过交叉筛选,共筛选出50个候选基因。机器学习确定了两个关键基因MUC16和DEFA5。构造了具有较强预测能力的nomogram。免疫细胞分析显示两种类型的差异免疫细胞-活化的树突状细胞和浆细胞-其中活化的树突状细胞在病例组中表达更高,浆细胞与DEFA5表现出强烈的正相关。此外,与对照组相比,MUC16在HD患者中显着过表达,而DEFA5表现出下调。结论:MUC16和DEFA5是HD和MAM相关的关键基因,并具有较高的预测准确率。这些发现为HD的机制和潜在治疗靶点提供了新的见解。
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来源期刊
International Journal of General Medicine
International Journal of General Medicine Medicine-General Medicine
自引率
0.00%
发文量
1113
审稿时长
16 weeks
期刊介绍: The International Journal of General Medicine is an international, peer-reviewed, open access journal that focuses on general and internal medicine, pathogenesis, epidemiology, diagnosis, monitoring and treatment protocols. The journal is characterized by the rapid reporting of reviews, original research and clinical studies across all disease areas. A key focus of the journal is the elucidation of disease processes and management protocols resulting in improved outcomes for the patient. Patient perspectives such as satisfaction, quality of life, health literacy and communication and their role in developing new healthcare programs and optimizing clinical outcomes are major areas of interest for the journal. As of 1st April 2019, the International Journal of General Medicine will no longer consider meta-analyses for publication.
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