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
英文原题:A bioinformatics analysis and experimental validation of PDGFD as a promising diagnostic biomarker for acute myeloid leukemia.
A bioinformatics analysis and experimental validation of PDGFD as a promising diagnostic biomarker for acute myeloid leukemia.
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。
急性髓系白血病(AML)是一种由白血病干细胞(LSCs)取代正常干细胞而导致的恶性血液肿瘤。血小板衍生生长因子(PDGFs)对LSCs具有重要作用,但在AML发生发展中尚未被研究。
本研究从癌症基因组图谱(TCGA)和GTEx数据库获取PDGFs的转录组数据,并使用R软件包和在线工具(UCSC-Xena Shiny工具、GEPIA2、Kaplan-Meier Plotter数据库等)进行相关差异表达和预后分析。随后,我们聚焦于PDGFD在AML中的表达,及其临床和诊断意义、耐药研究以及与免疫治疗的关联。采用实时定量聚合酶链反应(RT-qPCR)验证PDGFD的表达和临床特征。公共数据和临床样本分析显示,与其他PDGF基因相比,PDGFD表达上调,且仅此上调与AML不良预后相关。PDGFD高表达与中高危细胞遗传学风险、NPM1突变、FLT3-ITD突变及不良预后呈显著正相关。ROC曲线分析表明PDGFD对AML患者具有重要的诊断潜力。功能富集分析揭示了PDGFD在钙和Rap1信号通路中的作用。
此外,PDGFD表达与NK 细胞和树突状细胞呈显著正相关。进一步地,我们提出靶向PDGFD的MiR-203-3p在AML中具有潜在的抗白血病作用。
总之,PDGFD可作为AML可能的诊断和预后生物标志物,以及细胞免疫治疗的靶点。
Acute myeloid leukemia (AML) is a malignant blood cancer resulting from leukemia stem cells (LSCs) supplanting normal stem cells. Platelet-derived growth factors (PDGFs) are important for LSCs but have not been studied in the development of AML. In this study, transcriptome data of PDGFs were sourced from The Cancer Genome Atlas (TCGA) and GTEx databases, and relevant differential expression and prognosis analysis were performed using R software packages and online tools (UCSC-Xena Shiny tools, GEPIA2, Kaplan-Meier Plotter databases, etc.) . Then, we focused on PDGFD expression in AML, along with its clinical and diagnostic importance, drug resistance studies, and association with immunotherapy.
The real-time quantitative polymerase chain reaction (RT-qPCR) was performed to verify the expression and clinical characteristics of PDGFD. Analyses of public data and clinical samples revealed that PDGFD expression was upregulated compared with other PDGF genes, and only this upregulation was associated with poor prognosis in AML.
High expression of PDGFD showed a significant positive correlation with intermediate-high cytogenetic risk, NPM1 mutation, FLT3-ITD mutation, and unfavorable prognosis. ROC curve analysis indicated that PDGFD holds substantial diagnostic potential for AML patients. Functional enrichment analysis revealed the role of PDGFD in calcium and Rap1 signaling pathways.
Additionally, PDGFD expression exhibited a significant positive correlation with natural killer cells and dendritic cells.
Furthermore, we propose that MiR-203-3p targeting PDGFD has potential anti-leukemic effects in AML.
In conclusion, PDGFD serves as a possible diagnostic and prognostic biomarker, as well as a target for cellular immunotherapy in AML.
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 →
MEMBER ACCOUNT
登录成功会直接打开下一页。