NF-κB 信号通路相关长非编码 RNA 与宫颈癌肿瘤微环境和预后的关联。

The linkage of NF-κB signaling pathway-associated long non-coding RNAs with tumor microenvironment and prognosis in cervical cancer.

机构信息

Department of Reproductive Medicine, The First Affiliated Hospital of Harbin Medical University, Harbin, 150010, China.

Department of Medical Psychology, Harbin Medical University, Harbin, 150010, China.

出版信息

BMC Med Genomics. 2023 Jul 17;16(1):169. doi: 10.1186/s12920-023-01605-9.

DOI:10.1186/s12920-023-01605-9

PMID:37461017

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10351132/

Abstract

BACKGROUND

NF-κB signaling pathway participate closely in regulating inflammation and immune response in many cancers. Long non-coding RNAs (lncRNAs) associated with NF-κB signaling have not been characterized in cervical cancer. This study revealed the linkage between tumor microenvironment and NF-κB signaling-associated lncRNAs in cervical cancer.

MATERIALS AND METHODS

The expression profiles of cervical cancer samples from The Cancer Genome Atlas (TCGA) database were downloaded. NF-κB signaling-associated lncRNAs were screened as a basis to perform molecular subtyping. Immune cell infiltration was assessed by ESTIMATE, Microenvironment Cell Populations (MCP)-counter and single sample gene set enrichment analysis (ssGSEA). The key NF-κB signaling-associated lncRNAs were identified by univariate analysis, least absolute shrinkage and selection operator, and stepAIC.

RESULTS

Three molecular subtypes or clusters (cluster 3, cluster 2, and cluster 1) were categorized based on 27 prognostic NF-κB signaling-associated lncRNAs. Cluster 2 had the worst prognosis, highest immune infiltration, as well as the highest expression of most of immune checkpoints. Three clusters showed different sensitivities to immunotherapy and chemotherapy. Six key NF-κB signaling-associated lncRNAs were screened to establish a six-lncRNA risk model for predicting cervical cancer prognosis.

CONCLUSIONS

NF-κB signaling-associated lncRNAs played an important role in regulating immune microenvironment. The subtyping based on NF-κB signaling-associated lncRNAs may assist in the selection of optimal treatments. The six key NF-κB signaling-associated lncRNAs could act as prognostic biomarkers in prognostic prediction for cervical cancer.

摘要

背景

NF-κB 信号通路在许多癌症中密切参与调控炎症和免疫反应。与 NF-κB 信号相关的长非编码 RNA（lncRNA）在宫颈癌中尚未得到描述。本研究揭示了宫颈癌中肿瘤微环境与 NF-κB 信号相关 lncRNA 之间的联系。

材料与方法

从癌症基因组图谱（TCGA）数据库下载宫颈癌样本的表达谱。筛选与 NF-κB 信号相关的 lncRNA 作为进行分子亚型分析的基础。通过 ESTIMATE、Microenvironment Cell Populations（MCP）-counter 和单样本基因集富集分析（ssGSEA）评估免疫细胞浸润。通过单变量分析、最小绝对值收缩和选择算子（least absolute shrinkage and selection operator，LASSO）和 stepAIC 鉴定关键 NF-κB 信号相关 lncRNA。

结果

基于 27 个与 NF-κB 信号相关的预后 lncRNA，将三个分子亚型或簇（cluster 3、cluster 2 和 cluster 1）进行分类。cluster 2 预后最差，免疫浸润最高，大多数免疫检查点表达也最高。三个簇对免疫治疗和化疗的敏感性不同。筛选出六个关键的 NF-κB 信号相关 lncRNA 以建立预测宫颈癌预后的六 lncRNA 风险模型。