为肝细胞癌武装 GPC3 CAR-T 细胞:多少才足够,下一步是什么?
Armouring GPC3 CAR T cells for hepatocellular carcinoma: how much is enough and what comes next?
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 N6-methyladenosine -related long non-coding RNAs and immune cell infiltration in hepatocellular carcinoma.
Comprehensive analysis of N6-methyladenosine -related long non-coding RNAs and immune cell infiltration in hepatocellular carcinoma.
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我们旨在阐明N6-甲基腺苷(m6A)长链非编码RNA(lncRNA)及免疫细胞浸润在肝细胞癌(HCC)中的影响。通过使用PERL和R包进行基因表达分析,确定了lncRNA与m6A的关系。通过基因集富集分析进行了京都基因与基因组百科全书基因表达富集分析。利用Lasso回归构建预后模型。分析肿瘤微环境差异和免疫相关性,以阐明不同聚类中的免疫细胞浸润及其与临床预后的相关性。共表达分析显示,lncRNA表达与m6A密切相关。许多lncRNA是HCC预后的预测风险因素。m6A-lncRNA在肿瘤组织中部分高表达,可用于预后模型预测HCC预后,且独立于其他临床特征。根据GSEA,'NOTCH SIGNALING PATHWAY'富集最为显著。CKLF样MARVEL跨膜结构域包含成员3(CMTM3)在肿瘤组织中过表达。免疫细胞,如活化的CD4记忆T细胞、CD8 T细胞和滤泡辅助T细胞,在聚类2中高度浸润组织。聚类2中所有相关评分均较高,表明肿瘤细胞纯度较低,肿瘤微环境中免疫相关细胞密度较高。m6A-lncRNA与HCC的发生和进展密切相关。相应的预后模型有助于预测HCC预后。m6A-lncRNA及肿瘤微环境中相关的免疫细胞浸润可为HCC提供新的治疗靶点,需进一步研究。[图:见文本]。
We aimed to illustrate the influence of N6-methyladenosine (m6A) long non-coding RNAs (lncRNAs) and immune cell infiltration in hepatocellular carcinoma (HCC). The relationship of lncRNAs and m6A was identified through gene expression analysis using PERL and R packages. The Kyoto Encyclopedia of Genes and Genomes gene expression enrichment analysis was performed via gene set enrichment analysis. Lasso regression was utilized to construct prognostic model. Differences in the tumor microenvironment and the immune correlation were analyzed to clarify immune cell infiltration in different clusters and their correlation with the clinical prognosis. Co-expression analysis showed that lncRNA expression was associated closely with m6A. Many lncRNAs were predictive risk factors of prognosis in HCC.
m6A-lncRNAs were partially highly expressed in tumor tissue and could be used in a prognostic model to predict HCC prognosis, independent of other clinical characteristics. 'NOTCH SIGNALING PATHWAY' was most significantly enriched according to GSEA. CKLF-like MARVEL transmembrane domain-containing member 3 (CMTM3) was overexpressed in tumor tissue. Immune cells, such as activated CD4 memory T cells, CD8 T cells, and follicular helper T cells, highly infiltrated tissues in cluster 2.
All related scores were higher in cluster 2, indicating a lower purity of tumor cells and higher density of immune-related cells in the tumor microenvironment. m6A-lncRNAs are closely related to HCC occurrence and progression. Corresponding prognostic models can help predict HCC prognosis. m6A-lncRNAs and the related immune cell infiltration in the tumor microenvironment can provide novel therapeutic targets in HCC that need to be further studied. [Figure: see text].
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