Lu Jicheng, Lu Xu, Chen Bin
Department of Oncology, Suzhou Ninth People's Hospital, Suzhou, 215200, China.
Department of Radiotherapy, Suzhou Ninth People's Hospital, Suzhou, 215200, China.
Endocr Metab Immune Disord Drug Targets. 2025 Jan 8. doi: 10.2174/0118715303355042241208171133.
Liquid-Liquid Phase Separation (LLPS) is a process involved in the formation of established organelles and various condensates that lack membranes; however, the relationship between LLPS and Ulcerative Colitis (UC) remains unclear.
This study aimed to comprehensively clarify the correlation between ulcerative colitis (UC) and liquid-liquid phase separation (LLPS).
In this study, bioinformatics analyses and public databases were applied to screen and validate key genes associated with LLPS in UC. Furthermore, the roles of these key genes in UC were comprehensively analyzed.
Based on the single-cell transcriptomic data of UC obtained from the Gene Expression Omnibus (GEO) database, differences between patients with UC and their controls were compared using the limma package. The single-cell data were then filtered and normalized by the 'Seurat' package and subjected to dimension reduction by the Uniform Manifold Approximation and Projection (UMAP) algorithm. The LLPS-related genes (LLPSRGs) were searched on the Dr- LLPS website to obtain cross-correlated genes, which were scored using the ssGSEA algorithm. Next, functional enrichment, interaction network, immune landscape, and diagnostic and drug prediction of the LLPSRGs were comprehensively explored. Finally, the results were validated using external datasets and quantitative real-time PCR (qRT-PCR).
A total of eight cell types in UC were classified, namely, fibroblasts, macrophages, endothelial cells, neutrophils, NK cells, B cells, epithelial cells, and T cells. The intersection between differently expressed genes (DEGs) among the eight cell types identified 44 key genes, which were predominantly enriched in immune- and infection-related pathways. According to receiver operating characteristic (ROC) curves, PLA2G2A, GZMK, CD69, HSP90B1, and S100A11 reached an AUC value of 0.94, 0.95, 0.86, 0.89, and 0.93, respectively. Drug prediction revealed that decitabine, tetrachlorodibenzodioxin, tetradecanoylphorbol acetate, thapsigargin, and cisplatin were the potential small molecular compounds for PLA2G2A, GZMK, CD69, HSP90B1, and S100A11. Immune cell infiltration analysis demonstrated that the infiltration of CD4 memory T cell activation, macrophage M1, T macrophage M0, neutrophils, and mast cell activation was higher in the UC group than in the normal group.
The LLPSRGs play crucial roles in UC and can be used as prognostic and diagnostic markers for UC. The current findings contribute to the management of UC.
液-液相分离（LLPS）是一个参与形成成熟细胞器和各种无膜凝聚物的过程；然而，LLPS与溃疡性结肠炎（UC）之间的关系仍不清楚。
本研究旨在全面阐明溃疡性结肠炎（UC）与液-液相分离（LLPS）之间的相关性。
在本研究中，应用生物信息学分析和公共数据库来筛选和验证与UC中LLPS相关的关键基因。此外，还全面分析了这些关键基因在UC中的作用。
基于从基因表达综合数据库（GEO）获得的UC单细胞转录组数据，使用limma软件包比较UC患者与其对照组之间的差异。然后，通过'Seurat'软件包对单细胞数据进行过滤和标准化，并通过均匀流形近似和投影（UMAP）算法进行降维。在Dr-LLPS网站上搜索LLPS相关基因（LLPSRGs）以获得交叉相关基因，使用ssGSEA算法对其进行评分。接下来，全面探索LLPSRGs的功能富集、相互作用网络、免疫景观以及诊断和药物预测。最后，使用外部数据集和定量实时PCR（qRT-PCR）对结果进行验证。
UC中共分类出八种细胞类型，即成纤维细胞、巨噬细胞、内皮细胞、中性粒细胞、自然杀伤细胞、B细胞、上皮细胞和T细胞。八种细胞类型中差异表达基因（DEGs）的交集确定了44个关键基因，这些基因主要富集在免疫和感染相关途径中。根据受试者工作特征（ROC）曲线，PLA2G2A、GZMK、CD69、HSP90B1和S100A11的AUC值分别达到0.94、0.95、0.86、0.89和0.93。药物预测显示，地西他滨、四氯二苯并二恶英、十四酰佛波醇乙酸酯、毒胡萝卜素和顺铂是PLA2G2A、GZMK、CD69、HSP90B1和S100A11的潜在小分子化合物。免疫细胞浸润分析表明，UC组中CD4记忆T细胞活化、巨噬细胞M1、T巨噬细胞M0、中性粒细胞和肥大细胞活化的浸润高于正常组。
LLPSRGs在UC中起关键作用，可作为UC的预后和诊断标志物。目前的研究结果有助于UC的管理。
