RNF43 p.G659fs 通过 PI3K/AKT/mTOR 信号通路和 HLA-E 上调导致 MSI-high 结直肠癌中 NK 细胞功能障碍
RNF43 p.G659fs leads to natural killer cell dysfunction in MSI-high colorectal cancer through PI3K/AKT/mTOR signaling and HLA-E up-regulation.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
通过 bulk 和单细胞 RNA 测序分析鉴定和验证与肺腺癌 M2 巨噬细胞和血红素代谢相关的预后基因
英文原题：Identification and validation of prognostic genes associated with M2 macrophage and heme metabolism in lung adenocarcinoma through bulk and single-cell RNA sequencing analysis.
查看英文原题
Identification and validation of prognostic genes associated with M2 macrophage and heme metabolism in lung adenocarcinoma through bulk and single-cell RNA sequencing analysis.
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研究概要
本研究确定了 LUAD 的五个预后基因，为预后标志物和靶向治疗的开发提供了有价值的见解。
研究思路结论见上方概要
背景
研究已证实M2巨噬细胞和血红素代谢在癌症发展中的关键作用。本研究旨在识别并验证与肺腺癌（LUAD）中M2巨噬细胞及血红素代谢相关基因（HMRGs）相关的预后基因，为靶向治疗策略的进展提供有价值的见解。
方法
LUAD相关数据集来源于公共数据库。首先，通过免疫浸润、相关性分析和回归分析确定了预后基因。随后，建立并评估了一个风险模型。最后，进行了体细胞突变分析、免疫治疗评估、单细胞RNA测序（scRNA-seq）和免疫组织化学（IHC）分析。
结果
在本研究中，EPB41、ACP5、PPOX、RBM38 和 TRIM58 被确定为 LUAD 的预后基因。构建了一个风险模型，将患者分为高风险组（HRG）和低风险组（LRG），HRG 患者表现出更差的生存结局。体细胞突变分析显示，TP53（49%）和 TTN（44%）是 HRG 和 LRG 样本中最常见的突变基因。此外，B 细胞、M2 巨噬细胞、NK 细胞、CD8 T 细胞和调节性 T 细胞（Tregs）在 HRG 样本中浸润显著更高，而 CD4 T 细胞在 HRG 样本中浸润显著更低。此外，发现 ACP5 与所有免疫检查点均呈强正相关。最后，scRNA-seq 鉴定出 14 种注释细胞类型，其中 ACP5 在 M2 巨噬细胞中表现出独特的表达。
展开英文摘要原文
BACKGROUND
Research has demonstrated the pivotal role of M2 macrophages and heme metabolism in cancer development. This study aimed to identify and validate prognostic genes linked to M2 macrophages and heme metabolism-related genes (HMRGs) in lung adenocarcinoma (LUAD), offering valuable insights for the advancement of targeted therapeutic strategies.
METHODS
LUAD-related datasets were sourced from public databases. Initially, prognostic genes were ascertained through immune infiltration, correlation analysis, and regression analyses. A risk model was subsequently developed and evaluated. Finally, somatic mutation analysis, immunotherapy assessment, single-cell RNA sequencing (scRNA-seq), and immunohistochemical (IHC) analyses were conducted.
RESULTS
In this study, EPB41, ACP5, PPOX, RBM38, and TRIM58 were identified as prognostic genes for LUAD. A risk model was developed to stratify patients into high-risk groups (HRG) and low-risk groups (LRG), with HRG patients demonstrating poorer survival outcomes. Somatic mutation analysis revealed that TP53 (49%) and TTN (44%) were the most frequently mutated genes in both HRG and LRG samples. Furthermore, B cells, M2 macrophages, natural killer cells (NK), CD8 T cells, and regulatory T cells (Tregs) exhibited significant higher infiltration in HRG samples, whereas CD4 T cells exhibited notably lower infiltration in HRG samples. Additionally, ACP5 was found to have strong positive correlations with all immune checkpoints. Finally, scRNA-seq identified 14 annotated cell types, with ACP5 showing distinct expression in M2 macrophages.
CONCLUSION
This study identified five prognostic genes for LUAD, offering valuable insights that could contribute to the development of prognostic markers and targeted therapies.
论文信息
- 作者
- Li J、Bai X、Long J、Wang J、Zhang C、Wang H、Hei R、Ma J
- 第一作者单位
- Department of General Thoracic Surgery, General Hospital of Ningxia Medical University, Yinchuan, 750004, China.China
- 通讯作者单位
- Department of Human Anatomy, Histology and Embryology, School of Basic Medicine, Ningxia Medical University, Yinchuan, 750004, China. MLJ2026@hotmail.com.China
- 期刊
- Discover oncology2026 Mar 5
- 原文标识
- PubMed 41787185 · DOI 10.1007/s12672-026-04742-6
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