鉴定 m6A 相关 lncRNAs 作为结直肠癌肿瘤免疫微环境中的预后标志物。

Identification of m6A-related lncRNAs as prognostic signature within colon tumor immune microenvironment.

机构信息

Provincial Key Laboratory of Biotechnology of Shaanxi Province, Northwest University, Xi'an, China.

Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, School of Life Sciences, Northwest University, Xi'an, China.

出版信息

Cancer Rep (Hoboken). 2023 Jun;6(6):e1828. doi: 10.1002/cnr2.1828. Epub 2023 May 13.

DOI:10.1002/cnr2.1828

PMID:37178411

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10242659/

Abstract

BACKGROUND

The current study probed prognosis-related potential for m6A-related lncRNAs signatures within colon tumor immune microenvironment (TIM).

METHODS

After downloading transcriptomic datasets for colon cancer (CC) patients from The Cancer Genome Atlas (TCGA), they were divided, in a 1:1 ratio, within training or test datasets. m6A-related lncRNAs were then scrutinized across such dataset using Pearson correlation assessment before generating a m6A-related lncRNAs prognosis-related model using the training dataset. The latter was then validated with the test and the whole dataset. In addition, we compared the differences of TIM and the estimated IC50 of drug response between the high- and low-risk groups.

RESULTS

Overall survival (OS) resulted as linked with 11 m6A-related lncRNAs, while within the developed prognosis-related model, areas-under-curves were as follows: within training dataset, values at 3-, 4-, and 5-years were 0.777, 0.819, and 0.805, accordingly, and for test one, they were 0.697, 0.682, and 0.706, respectively. Finally, the values for the whole dataset were 0.675 (3-year), 0.682 (4-years), and 0.679 (5-years), accordingly. Moreover, CC cases categorized within low-risk cohort demonstrated enhanced OS (p < .0001), lower metastasis (p = 2e-06) and lower T stage (p = .0067), more instability for microsatellite status (p = .012), and downregulation for PD-L1, PD-1, CTLA-4, LAG3, and HAVCR2 (p < .05). In addition, risk scorings were significantly linked to the degree of infiltrative intensity for CD8 and CD4 (memory resting) T-cells, T-regulatory (Tregs), and Mast cells triggering (p < .05). Patients with low infiltrative propensity for CD4 T-cells also had better OS (p = .016). Moreover, six representative drugs were found to be sensitive for treating CC patients.

CONCLUSION

A robust m6A-related prognostic model with great performances was developed before exploring the TIM characteristics and its potential therapeutic drugs, which might improve the prognosis and therapeutic efficacy.

摘要

背景

本研究旨在探讨结肠癌肿瘤免疫微环境（TIM）中 m6A 相关长链非编码 RNA 标志物的预后相关潜能。

方法

从癌症基因组图谱（TCGA）下载结肠癌（CC）患者的转录组数据集后，将其按照 1:1 的比例分为训练或测试数据集。然后使用 Pearson 相关性评估在这些数据集中筛选 m6A 相关 lncRNAs，之后使用训练数据集生成 m6A 相关 lncRNAs 预后相关模型。然后使用测试数据集和全数据集对该模型进行验证。此外，我们还比较了高低风险组之间 TIM 和药物反应估计 IC50 的差异。

结果

总生存期（OS）与 11 个 m6A 相关 lncRNAs 相关，而在开发的预后相关模型中，曲线下面积如下：在训练数据集中，3 年、4 年和 5 年的数值分别为 0.777、0.819 和 0.805，在测试数据集中，相应数值分别为 0.697、0.682 和 0.706，在全数据集的相应数值分别为 0.675（3 年）、0.682（4 年）和 0.679（5 年）。此外，低风险组的 CC 病例具有更高的 OS（p<0.0001）、更低的转移（p=2e-06）和更低的 T 分期（p=0.0067）、微卫星状态更不稳定（p=0.012）以及 PD-L1、PD-1、CTLA-4、LAG3 和 HAVCR2 的表达下调（p<0.05）。此外，风险评分与 CD8 和 CD4（记忆静止）T 细胞、T 调节（Treg）和 Mast 细胞触发的浸润强度显著相关（p<0.05）。CD4 T 细胞浸润性低的患者 OS 更好（p=0.016）。此外，还发现六种代表性药物对治疗 CC 患者敏感。