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使用整合的单细胞和批量RNA测序对结直肠癌中乙酰化的分子特征进行全面表征。

Comprehensive characterization of the molecular feature of acetylation in colorectal cancer using integrated single-cell and bulk RNA sequencing.

作者信息

Li Kai, Song Wei, Zhang Yuefeng, Luo Jianfei

机构信息

Department of Gastrointestinal Surgery, Renmin Hospital of Wuhan University, No. 238, Jiefang Road, Wuhan, 430060, Hubei, China.

Department of Hepatobiliary Surgery, Renmin Hospital of Wuhan University, Wuhan, 430060, Hubei, China.

出版信息

Sci Rep. 2025 Sep 23;15(1):32638. doi: 10.1038/s41598-025-21081-8.

Abstract

Colorectal cancer (CRC) remains a major global health burden with high mortality rates, underscoring the need for effective therapies. This study explores the acetylation characteristics in CRC using single-cell RNA sequencing (scRNA-seq) and weighted gene co-expression network analysis (WGCNA), assessing their relationship with prognosis and the immune microenvironment. We analyzed two scRNA-seq datasets from the GEO database to identify distinct cell subtypes. Acetylation activity scores were calculated using the ssGSEA method. A WGCNA was constructed to identify gene modules associated with acetylation. An acetylation-related prognostic signature (ARPS) was developed, and its clinical significance was evaluated through survival analysis and immune landscape characterization. Acetylation activity was significantly elevated in epithelial, endothelial, and stromal cells. Based on the results of scRNA-seq, WGCNA identified 169 acetylation-related genes. Intersection with 1,691 acetylation-related differentially expressed genes (DEGs) yielded 131 common genes. Combining clinical data with the expression profiles of these genes, we employed 101 machine learning algorithms to develop an ARPS that accurately predicts the prognosis of CRC patients. Low-risk patients showed increased infiltration of immune cells, enhanced immune function, and better responses to immunotherapy. These findings underscore the clinical significance of acetylation features in CRC prognosis and immune response, highlighting their potential as biomarkers and therapeutic targets.

摘要

结直肠癌(CRC)仍然是一个主要的全球健康负担,死亡率很高,这突出了对有效治疗方法的需求。本研究利用单细胞RNA测序(scRNA-seq)和加权基因共表达网络分析(WGCNA)探索CRC中的乙酰化特征,评估它们与预后和免疫微环境的关系。我们分析了来自GEO数据库的两个scRNA-seq数据集,以识别不同的细胞亚型。使用ssGSEA方法计算乙酰化活性评分。构建WGCNA以识别与乙酰化相关的基因模块。开发了一种乙酰化相关预后特征(ARPS),并通过生存分析和免疫景观特征评估其临床意义。上皮细胞、内皮细胞和基质细胞中的乙酰化活性显著升高。基于scRNA-seq的结果,WGCNA识别出169个与乙酰化相关的基因。与1691个与乙酰化相关的差异表达基因(DEG)相交,得到131个共同基因。将临床数据与这些基因的表达谱相结合,我们采用101种机器学习算法开发了一种ARPS,能够准确预测CRC患者的预后。低风险患者显示免疫细胞浸润增加、免疫功能增强以及对免疫治疗的反应更好。这些发现强调了乙酰化特征在CRC预后和免疫反应中的临床意义,突出了它们作为生物标志物和治疗靶点的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2135/12457583/8903a9040bb9/41598_2025_21081_Fig1_HTML.jpg

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