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结直肠癌中N6-甲基腺苷相关长链非编码RNA的免疫浸润与PD-L1表达的综合分析

Integrated Analysis of the Immune Infiltrates and PD-L1 Expression of N6-Methyladenosine-Related Long Non-Coding RNAs in Colorectal Cancer.

作者信息

Jiang Ziting, Zhang Yitong, Chen Ke, Yang Xiujiang, Liu Jianqiang

机构信息

Department of Endoscopy, Fudan University Shanghai Cancer Center, Shanghai, People's Republic of China.

Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China.

出版信息

Int J Gen Med. 2021 Aug 29;14:5017-5028. doi: 10.2147/IJGM.S327765. eCollection 2021.

Abstract

BACKGROUND

N6-methyladenosine-related long non-coding RNAs (m6A-related lncRNAs) are involved in the occurrence and progression of various cancers. However, it remains unclear whether m6A-related lncRNAs have potential roles in tumor immune microenvironment (TIME).

METHODS

Herein, we investigated correlations of prominent m6A-related lncRNAs with immune infiltrates and PD-L1 expression and the prognostic value of m6A-related lncRNAs in colorectal cancer from The Cancer Genome Atlas (TCGA) cohort, systematically.

RESULTS

Firstly, we conducted Pearson correlation analysis to screen the m6A-related lncRNAs, and then univariate Cox regression analysis was performed to identify 72 prognostic m6A-related lncRNAs in CRC patients. Moreover, two molecular subtypes (cluster 1/2) were identified by consensus clustering for 72 m6A-related lncRNAs. The cluster 1 preferentially associated with favorable prognosis, upregulated PD-L1 expression, higher immunoscore, and distinct immune cell infiltration. Furthermore, a prognostic risk score was calculated using 19 m6A-related lncRNAs based signatures which represented an independent prognostic factor for CRC. Patients with low-risk score showed higher PD-L1 expression than patients with high-risk score. Further analysis revealed that m6A-related lncRNAs based signatures were associated with tumor-infiltrating immune cells.

CONCLUSION

Our study indicated the essential roles of m6A-related lncRNAs in TIME of CRC and provide novel insights in our understanding of m6A-related lncRNAs function in colorectal cancer.

摘要

背景

N6-甲基腺苷相关的长链非编码RNA(m6A相关lncRNA)参与多种癌症的发生和发展。然而,m6A相关lncRNA在肿瘤免疫微环境(TIME)中是否具有潜在作用仍不清楚。

方法

在此,我们系统地研究了显著的m6A相关lncRNA与免疫浸润和PD-L1表达的相关性,以及m6A相关lncRNA在癌症基因组图谱(TCGA)队列中的结直肠癌预后价值。

结果

首先,我们进行Pearson相关分析以筛选m6A相关lncRNA,然后进行单变量Cox回归分析以鉴定CRC患者中72个预后m6A相关lncRNA。此外,通过对72个m6A相关lncRNA进行一致性聚类,鉴定出两种分子亚型(簇1/2)。簇1优先与良好预后、上调的PD-L1表达、更高的免疫评分和独特的免疫细胞浸润相关。此外,使用基于19个m6A相关lncRNA的特征计算预后风险评分,其代表CRC的独立预后因素。低风险评分患者的PD-L1表达高于高风险评分患者。进一步分析表明,基于m6A相关lncRNA的特征与肿瘤浸润免疫细胞相关。

结论

我们的研究表明m6A相关lncRNA在CRC的TIME中起重要作用,并为我们理解m6A相关lncRNA在结直肠癌中的功能提供了新的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bf03/8412838/d07d24d3fdf9/IJGM-14-5017-g0001.jpg

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