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:Integrative single-cell transcriptomics and co-expression network analysis identify SIMALR as a prognostic immune-related lncRNA in breast cancer: in silico analysis and validation.
Integrative single-cell transcriptomics and co-expression network analysis identify SIMALR as a prognostic immune-related lncRNA in breast cancer: in silico analysis and validation.
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本研究旨在识别和表征与乳腺癌预后和免疫调节相关的irlncRNAs。我们整合了单细胞RNA测序、hdWGCNA和bulk RNA-seq差异表达分析结果,以识别候选irlncRNAs。对排名最高的候选分子SIMALR,进一步通过免疫分析、生存分析、突变分析和GSEA进行了研究。对患者组织进行了RT-qPCR初步验证。SIMALR与良好的生存相关,并富集于免疫通路,包括T细胞受体信号传导、自然杀伤(NK)细胞细胞毒性和抗原加工。Pearson分析显示SIMALR相关基因(CD8A、CD4、TNF、LCP2、ITGB2)在关键免疫细胞群中共表达。肿瘤细胞中SIMALR高表达与Th1招募趋化因子(CXCL9/10/11、CCL5)分泌增强、CD8+ T细胞招募、活化树突状细胞以及M1/M2巨噬细胞相关。RT-qPCR证实肿瘤中SIMALR表达较高。由于临床标本有限,RT-qPCR分析仅在六名患者的配对组织样本上进行,因此结果应视为初步验证。SIMALR可能有助于抗肿瘤免疫,突显其作为乳腺癌有前景的生物标志物和治疗靶点的潜力。
This study aimed to identify and characterize irlncRNAs associated with prognosis and immune modulation in breast cancer.
We integrated single-cell RNA sequencing, hdWGCNA, and bulk RNA-seq differential expression analysis results to identify candidate irlncRNAs. The top candidate, SIMALR, was further investigated using immune, survival, mutation analysis, and GSEA. RT-qPCR preliminary validation was performed on patient tissues. SIMALR was linked to favorable survival and enriched in immune pathways, including T-cell receptor signaling, Natural Killer (NK) cell cytotoxicity, and antigen processing. Pearson analysis showed co-expression of SIMALR-related genes (CD8A, CD4, TNF, LCP2, ITGB2) in key immune populations. High SIMALR As per standard instruction, "Statement of Significance" section should not be captured.
Hence, the "Clinical significance" section was deleted. Please check and confirm if presented correctly; otherwise, please amend. expression in tumor cells is associated with enhanced secretion of Th1-attracting chemokines (CXCL9/10/11, CCL5), recruitment of CD8 + T cells, activated dendritic cells, and both M1/M2 macrophages. RT-qPCR confirmed higher SIMALR expression in tumors.
Due to limited availability of clinical specimens, the RT-qPCR analysis was performed on paired tissue samples from six patients, and therefore the results should be considered a preliminary validation. SIMALR may contribute to anti-tumor immunity, highlighting its potential as a promising biomarker and therapeutic target in breast cancer.
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