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肺腺癌的两种RNA修饰模式鉴定及肿瘤微环境浸润特征分析

The Identification of Two RNA Modification Patterns and Tumor Microenvironment Infiltration Characterization of Lung Adenocarcinoma.

作者信息

He Wan, Lin Gengpeng, Pan Chaohu, Li Wenwen, Shen Jing, Liu Yangli, Li Hui, Wu Dongfang, Lin Xuejia

机构信息

Department of Oncology, Shenzhen People's Hospital, Shenzhen, China.

Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Sun Yat-sen University, Institute of Pulmonary Diseases, Sun Yat-sen University, Guangzhou, China.

出版信息

Front Genet. 2022 Jan 28;13:761681. doi: 10.3389/fgene.2022.761681. eCollection 2022.

DOI:10.3389/fgene.2022.761681
PMID:35154267
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8831702/
Abstract

RNA modification plays an important role in many diseases. A comprehensive study of tumor microenvironment (TME) characteristics mediated by RNA modification regulators will improve the understanding of TME immune regulation. We selected 26 RNA modification "writers" of lung adenocarcinoma (LUAD) samples and performed unsupervised clustering analysis to explore RNA modification patterns in LUAD. Differentially expressed genes (DEGs) with RNA modification patterns were screened to develop a "writers" of RNA modification score (WM score) system. The infiltration ratio of TME cell subsets was analyzed by CIBERSORT. We identified two RNA modification modes showing different characteristics of overall survival (OS) and TME cell infiltration. According to WM score, LUAD patients were divided into a high-WM score group and a low-WM score group. High-scored patients had a poor prognosis and higher tumor mutation burden (TMB), they were more sensitive to four LUAD therapies (erlotinib, XA V939, gefitinib, and KU-55933) and more clinically responsive to PD-L1 treatment. Those with a low WM score showed higher stromal scores, ESTIMATE scores, and survival chance. Our work revealed the potential role of RNA modification patterns in TME, genetic variation, targeted inhibitor therapy, and immunotherapy. Identifying RNA modification pattern of LUAD patients help understand the characteristics of TME and may promote the development of immunotherapy strategies.

摘要

RNA修饰在许多疾病中发挥着重要作用。对由RNA修饰调节因子介导的肿瘤微环境（TME）特征进行全面研究，将有助于提高对TME免疫调节的理解。我们选择了肺腺癌（LUAD）样本中的26种RNA修饰“书写器”，并进行了无监督聚类分析，以探索LUAD中的RNA修饰模式。筛选出具有RNA修饰模式的差异表达基因（DEG），以建立RNA修饰评分（WM评分）系统。通过CIBERSORT分析TME细胞亚群的浸润率。我们确定了两种显示出不同总生存期（OS）和TME细胞浸润特征的RNA修饰模式。根据WM评分，将LUAD患者分为高WM评分组和低WM评分组。高分患者预后较差且肿瘤突变负担（TMB）较高，他们对四种LUAD治疗（厄洛替尼、XA V939、吉非替尼和KU-55933）更敏感，对PD-L1治疗的临床反应性更高。低WM评分者显示出更高的基质评分、ESTIMATE评分和生存机会。我们的工作揭示了RNA修饰模式在TME、基因变异、靶向抑制剂治疗和免疫治疗中的潜在作用。识别LUAD患者的RNA修饰模式有助于了解TME的特征，并可能促进免疫治疗策略的发展。

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