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:Comprehensive analysis of the PD-L1 and immune infiltrates of N6-methyladenosine related long non-coding RNAs in bladder cancer.
Comprehensive analysis of the PD-L1 and immune infiltrates of N6-methyladenosine related long non-coding RNAs in bladder cancer.
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膀胱癌(BLCA)是最常见的泌尿生殖系统癌症之一,具有高发病率和死亡率。本研究广泛探讨了m6A相关lncRNA与PD-L1及肿瘤免疫微环境(TIME)在BLCA预后中的关联,这可能为进一步研究提示新的治疗靶点。通过共表达分析,从TCGA数据集中鉴定出30个具有预测价值的m6A相关lncRNA。Cluster2与不良预后、PD-L1表达上调及更高的免疫评分相关。Cluster2中静息CD4记忆活化T细胞、M2巨噬细胞、中性粒细胞和NK细胞浸润量更大。根据GSEA,“趋化因子信号通路”是最显著富集的信号通路,可能在cluster1/2之间不同免疫细胞浸润中发挥重要作用。m6A相关lncRNA的风险模型可用于预后模型以预测BLCA预后,且不受其他临床特征影响。
总体而言,m6A相关lncRNA与PD-L1和TIME相关,可动态影响肿瘤浸润免疫细胞的数量。m6A相关lncRNA可能是PD-L1表达和免疫细胞浸润的关键介质,并可能强烈影响BLCA的TIME。
Bladder cancer (BLCA) is one of the most frequent genitourinary cancers, with a high rate of morbidity and mortality. The connection of m6A-related lncRNAs with PD-L1 and tumor immune microenvironment (TIME) in BLCA prognosis was extensively investigated in this study, which could suggest novel therapeutic targets for further investigation. 30 m6A-associated lncRNAs with predictive values from the TCGA data set were identified with co-expression analysis. Cluster2 was correlated with a poor prognosis, upregulated PD-L1 expression, and higher immune ratings. Cluster2 had larger amounts of resting CD4 memory-activated T cells, M2 macrophages, neutrophils, and NK cells infiltration.
"CHEMOKINE SIGNALING PATHWAY" was the most significantly enriched signaling pathway according to GSEA, which may play an important role in the different immune cell infiltrates between cluster1/2. The risk model for m6A-related lncRNAs could be employed in a prognostic model to predict BLCA prognosis, regardless of other clinical features.
Collectively, m6A-related lncRNAs were linked to PD-L1 and TIME, which would dynamically affect the number of tumor-infiltrating immune cells. m6A-related lncRNAs may be key mediators of PD-L1 expression and immune cells infiltration and may strongly affect the TIME of BLCA.
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