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
非裔美国人和高加索美国人胰腺导管腺癌的差异基因表达谱
英文原题：Differential gene expression profiles of pancreatic ductal adenocarcinomas among African American and Caucasian American patients.
查看英文原题
Differential gene expression profiles of pancreatic ductal adenocarcinomas among African American and Caucasian American patients.
分数与星级只用于站内排序 —— 不代表疗效、安全性或个人适用性。
研究概要
这些发现显示了 AA 和 CA PDAC 中不同的基因表达谱和受调控的通路，支持基于种族的治疗靶点的开发。
研究思路结论见上方概要
目的
在美国，非裔美国人（AA）的胰腺导管腺癌（PDAC）发病率和死亡率高于白人美国人（CA）。本研究旨在识别AA和CA PDAC中不同的基因表达特征和差异调控通路。
方法
对来自AA（9例PDAC/3例正常）和CA（31例PDAC/5例正常）组织的PDAC（n = 40）FFPE切片进行了转录组分析，以评估种族组内和组间的差异表达和信号通路，并识别独特和共同的基因/通路。
结果
我们在两个种族群体中识别出独特的差异表达基因。与各自正常组织相比，AA和CA PDAC中调控了不同的基因集。在AA PDACs与CA PDACs比较中，有13个基因（7个上调，6个下调）受到差异性调控。CIBERSORT分析揭示了不同的免疫细胞组成，AA PDACs中静息NK细胞和活化肥大细胞增加，而CA PDACs中CD4记忆T细胞较高。经典亚型分析表明，AA PDACs中亚型分布更为异质，而CA PDACs则显示经典亚型占主导。利用公开数据库，我们分析了AA和CA种族群体中前25个上调基因（正常 vs. 肿瘤）以及AA PDACs与CA PDACs比较中7个差异上调基因与生存结局的关联。8个基因（CHST15、PARP15、NUDT16、SERPINB3、PADI1、H3C8、ZNF488和LETM2）与患者不良生存相关。
展开英文摘要原文
PURPOSE
In the United States, African Americans (AA) have higher Pancreatic ductal adenocarcinoma (PDAC) incidence and mortality rates than Caucasian Americans (CA). This study aimed to identify distinct gene expression signatures and differentially regulated pathways in AA and CA PDACs.
METHODS
Transcriptomic analyses were conducted on FFPE sections of PDACs (n = 40) from AA (9 PDACs/3 normal) and CA (31 PDACs/5 normal) tissues to evaluate the differential expression and signaling pathways within and between racial groups and to identify distinctive and common genes/pathways.
RESULTS
We identified unique differentially expressed genes in both racial groups. Distinct set genes were modulated in AA and CA PDACs, compared to their respective normal tissues. Thirteen genes (seven upregulated and six downregulated) were differentially modulated in AA PDACs vs. CA PDACs. CIBERSORT analysis revealed distinct immune cell composition, with increased resting NK cells and activated mast cells, in AA PDACs, and higher CD4 memory T cells present in CA PDACs. Canonical subtype analyses indicated a more heterogenous subtype distribution in AA PDACs, whereas CA PDACs showed a predominance of classical subtypes. Using a publicly available database, we analyzed the top 25 upregulated genes (normal vs. tumor) for AA and CA racial groups and seven differentially upregulated genes in AA PDACs vs. CA PDACs comparison for associations with survival outcomes. Eight genes (CHST15, PARP15, NUDT16, SERPINB3, PADI1, H3C8, ZNF488, and LETM2) correlated with poor patient survival.
CONCLUSION
These findings show distinct gene expression profiles and modulated pathways in AA and CA PDACs, supporting development of race-based therapeutic targets.
论文信息
- 作者
- Bajpai P、Paluri R、Diffalha SA、Chandrashekar DS、Afaq F、Otali D、Elkholy A、Miller CR
- 第一作者单位
- Department of Pathology, Division of Anatomic Pathology, University of Alabama at Birmingham, Birmingham, AL, USA.United States
- 通讯作者单位
- Department of Pathology, Division of Anatomic Pathology, University of Alabama at Birmingham, Birmingham, AL, USA; UAB O'Neal Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL, USA. Electronic address: upendermanne@uabmc.edu.United States
- 期刊
- Translational oncology2025 Sep
- 原文标识
- PubMed 40616988 · DOI 10.1016/j.tranon.2025.102466
在 PubMed 查看 → 出版商原文（DOI） 全文 PDF（PMC）· 可下载 治疗专题与资料阅读指南 资料来源与翻译说明 报告译文或资料问题 →