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口腔鳞状细胞癌患者的环状RNA相关竞争性内源RNA网络及预后标志物

Circular RNA-related CeRNA network and prognostic signature for patients with oral squamous cell carcinoma.

作者信息

He Yaodong, Yang Dengcheng, Li Yunshan, Xiang Junwei, Wang Liecheng, Wang Yuanyin

机构信息

Key Laboratory of Oral Diseases Research of Anhui Province, College and Hospital of Stomatology, Anhui Medical University, Hefei, China.

Department of Physiology, School of Basic Medical Sciences, Anhui Medical University, Hefei, China.

出版信息

Front Pharmacol. 2022 Dec 1;13:949713. doi: 10.3389/fphar.2022.949713. eCollection 2022.

Abstract

Circular RNA (circRNA) has an important influence on oral squamous cell carcinoma (OSCC) progression as competing endogenous RNAs (ceRNAs). However, the link between ceRNAs and the OSCC immune microenvironment is unknown. The research aimed to find circRNAs implicated in OSCC carcinogenesis and progression and build a circRNA-based ceRNA network to create a reliable OSCC risk prediction model. The expression profiles of circRNA in OSCC tumors and normal tissues were assessed through RNA sequencing. From the TCGA database, clinicopathological data and expression patterns of microRNAs (miRNAs) and mRNAs were obtained. A network of circRNA-miRNA-mRNA ceRNA was prepared according to these differentially expressed RNAs and was analyzed through functional enrichment. Subsequently, based on the mRNA in the ceRNA network, the influence of the model on prognosis was then evaluated using a risk prediction model. Finally, considering survival, tumor-infiltrating immune cells (TICs), clinicopathological features, immunosuppressive molecules, and chemotherapy efficacy were analyzed. Eleven differentially expressed circRNAs were found in cancer tissues relative to healthy tissues. We established a network of circRNA-miRNA-mRNA ceRNA, and the ceRNA network includes 123 mRNAs, six miRNAs, and four circRNAs. By the assessment of Genomes pathway and Kyoto Encyclopedia of Genes, it is found that in the cellular senescence, PI3K-AKT and mTOR signaling pathway mRNAs were mainly enrichment. An immune-related signature was created utilizing seven immune-related genes in the ceRNA network after univariate and multivariate analysis. The receiver operating characteristic of the nomogram exhibited satisfactory accuracy and predictive potential. According to a Kaplan-Meier analysis, the high-risk group's survival rate was signally lower than the group with low-risk. In addition, risk models were linked to clinicopathological characteristics, TICs, immune checkpoints, and antitumor drug susceptibility. The profiles of circRNAs expression of OSCC tissues differ significantly from normal tissues. Our study established a circRNA-associated ceRNA network associated with OSCC and identified essential prognostic genes. Furthermore, our proposed immune-based signature aims to help research OSCC etiology, prognostic marker screening, and immune response evaluation.

摘要

环状RNA(circRNA)作为竞争性内源性RNA(ceRNA)对口腔鳞状细胞癌(OSCC)的进展具有重要影响。然而,ceRNA与OSCC免疫微环境之间的联系尚不清楚。本研究旨在寻找与OSCC发生发展相关的circRNA,并构建基于circRNA的ceRNA网络,以创建可靠的OSCC风险预测模型。通过RNA测序评估OSCC肿瘤组织和正常组织中circRNA的表达谱。从TCGA数据库中获取临床病理数据以及微小RNA(miRNA)和信使RNA(mRNA)的表达模式。根据这些差异表达的RNA构建circRNA-miRNA-mRNA ceRNA网络,并进行功能富集分析。随后,基于ceRNA网络中的mRNA,使用风险预测模型评估该模型对预后的影响。最后,综合生存情况,分析肿瘤浸润免疫细胞(TIC)、临床病理特征、免疫抑制分子和化疗疗效。相对于健康组织,在癌组织中发现了11种差异表达的circRNA。我们建立了circRNA-miRNA-mRNA ceRNA网络,该ceRNA网络包含123个mRNA、6个miRNA和4个circRNA。通过基因组途径和京都基因与基因组百科全书评估发现,在细胞衰老过程中,PI3K-AKT和mTOR信号通路的mRNA主要富集。在单变量和多变量分析后,利用ceRNA网络中的7个免疫相关基因创建了一个免疫相关特征。列线图的受试者工作特征显示出令人满意的准确性和预测潜力。根据Kaplan-Meier分析,高危组的生存率明显低于低危组。此外,风险模型与临床病理特征、TIC、免疫检查点和抗肿瘤药物敏感性相关。OSCC组织的circRNA表达谱与正常组织有显著差异。我们的研究建立了与OSCC相关的circRNA-ceRNA网络,并鉴定了重要的预后基因。此外,我们提出的基于免疫的特征旨在帮助研究OSCC的病因、预后标志物筛选和免疫反应评估。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ca74/9753980/8fea84059430/fphar-13-949713-g001.jpg

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