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全面分析 N6-甲基腺苷相关长链非编码 RNA 特征,预测结直肠癌患者的预后和免疫细胞浸润。

Comprehensive Analysis of N6-Methyladenosine-Related lncRNA Signature for Predicting Prognosis and Immune Cell Infiltration in Patients with Colorectal Cancer.

机构信息

Department of General Surgery, The First Affiliated Hospital of Jinan University, Guangzhou 510632, China.

School of Basic Medicine, Jinan University, Guangzhou 510632, China.

出版信息

Dis Markers. 2021 Oct 28;2021:8686307. doi: 10.1155/2021/8686307. eCollection 2021.

Abstract

BACKGROUND

Colorectal cancer (CRC) is the third most common tumor worldwide. Aberrant N6-methyladenosine (m6A) modification can influence the progress of the CRC. Additionally, long noncoding RNA (lncRNA) plays a critical role in CRC and has a close relationship with m6A modification. However, the prognostic potential of m6A-related lncRNAs in CRC patients still remains to be clarified.

METHODS

We use "limma" R package, "glmnet" R package, and "survival" R package to screen m6A-related-lncRNAs with prognostic potential. Then, we comprehensively analysed and integrated the related lncRNAs in different TNM stages from TCGA database using the LASSO Cox regression. Meanwhile, the relationship between functional enrichment of m6A-related lncRNAs and immune microenvironment in CRC was also investigated using the TCGA database. A prognostic model was constructed and validated to determine the association between m6A-related lncRNAs in different TNM stages and the prognosis of CRC.

RESULT

We demonstrated that three related m6A lncRNAs in different TNM stages were associated with the prognosis of CRC patients. Patients from the TCGA database were classified into the low-risk and the high-risk groups based on the expression of these lncRNAs. The patients in the low-risk group had longer overall survival than the patients in the high-risk group ( < 0.001). We further constructed and validated a prognostic nomogram based on these genes with a C-index of 0.80. The receiver operating characteristic curves confirmed the predictive capacity of the model. Meanwhile, we also found that the low-risk group has the correlation with the dendritic cell (DC). Finally, we discovered the relationship between the m6A regulators and the three lncRNAs.

CONCLUSION

The prognostic model based on three m6A-related lncRNAs exhibits superior predictive performance, providing a novel prognostic model for the clinical evaluation of CRC patients.

摘要

背景

结直肠癌(CRC)是全球第三大常见肿瘤。异常的 N6-甲基腺苷(m6A)修饰会影响 CRC 的进展。此外,长链非编码 RNA(lncRNA)在 CRC 中发挥着关键作用,与 m6A 修饰密切相关。然而,m6A 相关 lncRNA 在 CRC 患者中的预后潜力仍有待阐明。

方法

我们使用“limma”R 包、“glmnet”R 包和“survival”R 包筛选具有预后潜力的 m6A 相关 lncRNA。然后,我们综合分析并整合了 TCGA 数据库中不同 TNM 分期的相关 lncRNA,使用 LASSO Cox 回归。同时,还利用 TCGA 数据库研究了 m6A 相关 lncRNA 与 CRC 免疫微环境之间的功能富集关系。构建并验证了一个预后模型,以确定不同 TNM 分期的 m6A 相关 lncRNA 与 CRC 患者预后之间的关系。

结果

我们证实了不同 TNM 分期的三个相关 m6A lncRNA 与 CRC 患者的预后相关。根据这些 lncRNA 的表达,将 TCGA 数据库中的患者分为低风险组和高风险组。低风险组患者的总生存期长于高风险组(<0.001)。我们进一步构建并验证了一个基于这些基因的预后列线图,其 C 指数为 0.80。受试者工作特征曲线证实了该模型的预测能力。同时,我们还发现低风险组与树突状细胞(DC)有关。最后,我们发现了 m6A 调节因子与三个 lncRNA 之间的关系。

结论

基于三个 m6A 相关 lncRNA 的预后模型具有优异的预测性能,为 CRC 患者的临床评估提供了一种新的预后模型。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d5bf/8568524/606a4e97566d/DM2021-8686307.001.jpg

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