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:Construction of an N6-methyladenosine lncRNA- and immune cell infiltration-related prognostic model in colorectal cancer.
Construction of an N6-methyladenosine lncRNA- and immune cell infiltration-related prognostic model in colorectal cancer.
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本文旨在阐明N6-甲基腺苷(m6A)长链非编码RNA(lncRNA)及免疫细胞浸润对结直肠癌(CRC)的影响。我们从癌症基因组图谱计划中下载了CRC的工作流型数据和xml格式的临床数据。利用Perl和R软件鉴定lncRNA与m6A之间的关系。进行了京都基因与基因组百科全书富集分析。利用Lasso回归构建预后模型。采用生存分析探讨m6A lncRNA聚类与临床生存数据之间的关系。通过肿瘤微环境差异分析和免疫相关性分析,确定不同聚类中免疫细胞浸润水平及其与临床预后的相关性。lncRNA的表达与m6A密切相关。单因素Cox回归分析显示lncRNA是预后的危险因素。差异表达分析表明m6A lncRNA在肿瘤组织中部分高表达。m6A lncRNA相关预后模型可独立预测CRC的预后。ECM_RECEPTOR_INTERACTION是最显著富集的基因集。PARP8在肿瘤组织和高风险聚类中过表达。CD4记忆T细胞、活化静息NK细胞和记忆B细胞在高风险聚类中高度聚集。所有评分在低风险组中均较高。m6A lncRNA与CRC的发生和进展密切相关。相应的预后模型可用于评估CRC的预后。m6A lncRNA及肿瘤微环境中相关免疫细胞浸润可为进一步研究提供新的治疗靶点。
The present paper aims to shed light on the influence of N6-methyladenosine (m6A) long non-coding RNAs (lncRNAs) and immune cell infiltration on colorectal cancer (CRC).
We downloaded workflow-type data and xml-format clinical data on CRC from The Cancer Genome Atlas project. The relationship between lncRNA and m6A was identified by using Perl and R software. Kyoto Encyclopedia of Genes and Genomes enrichment analysis was performed. Lasso regression was utilized to construct a prognostic model. Survival analysis was used to explore the relationship between clusters of m6A lncRNAs and clinical survival data. Differential analysis of the tumor microenvironment and an immune correlation analysis were used to determine immune cell infiltration levels in different clusters and their correlation with clinical prognosis. The expression of lncRNA was tightly associated with m6A. The univariate Cox regression analysis showed that lncRNA was a risk factor for the prognosis.
Differential expression analysis demonstrated that m6A lncRNAs were partially highly expressed in tumor tissue. m6A lncRNA-related prognostic model could predict the prognosis of CRC independently. "ECM_RECEPTOR_INTERACTION" was the most significantly enriched gene set. PARP8 was overexpressed in tumor tissue and high-risk cluster. CD4 memory T cells, activated resting NK cells, and memory B cells were highly clustered in the high-risk cluster.
All of the scores were higher in the low-risk group. m6A lncRNA is closely related to the occurrence and progression of CRC. The corresponding prognostic model can be utilized to evaluate the prognosis of CRC. m6A lncRNA and related immune cell infiltration in the tumor microenvironment can provide novel therapeutic targets for further research.
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