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下调的 ADARB1 在肺鳞癌中的作用。

Role of downregulated ADARB1 in lung squamous cell carcinoma.

机构信息

Department of Pharmacy, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.

Center for Molecular Medicine, Xiangya Hospital, Key Laboratory of Molecular Radiation Oncology of Hunan Province, Central South University, Changsha, Hunan 410008, P.R. China.

出版信息

Mol Med Rep. 2020 Mar;21(3):1517-1526. doi: 10.3892/mmr.2020.10958. Epub 2020 Jan 23.

Abstract

Non‑small cell lung cancer (NSCLC) is prevalent worldwide. Lung squamous cell carcinoma (LUSC) is one of the main subtypes of NSCLC yet, currently, few biomarkers are available for the diagnosis of LUSC. The present study aimed to investigate the expression and role of adenosine deaminase RNA specific B1 (ADARB1) in lung squamous cell carcinoma (LUSC). Integrative bioinformatics analysis was used to identify the effects of ADARB1 expression on the occurrence and prognosis of LUSC. The expression of ADARB1 was further examined by immunohistochemistry (IHC). Bioinformatics analysis suggested that ADARB1 was downregulated in LUSC, serving as a potential tumor suppressor, and these results were verified by IHC performed on a lung cancer tissue array. Clinical studies suggested that ADARB1 expression and methylation levels were significantly associated with patient characteristics in LUSC. Moreover, ADARB1 global methylation levels were upregulated in LUSC tissues compared with normal lung tissues. Higher methylation levels of cg24063645 were associated with shorter overall survival time of patients with LUSC. A negative correlation was identified between ADARB1 and epidermal growth factor receptor (EGFR) expression in LUSC. Using the Gene Expression Omnibus database, it was suggested that the expression of ADARB1 in LUSC was significantly different compared with that in lung adenocarcinoma. Furthermore, protein‑protein interactions were studied and a biological process annotation analysis was conducted. The present study suggested that ADARB1 was downregulated in LUSC; therefore, ADARB1 may serve as a specific biomarker and a potential therapeutic target for LUSC.

摘要

非小细胞肺癌(NSCLC)在全球范围内普遍存在。肺鳞状细胞癌(LUSC)是 NSCLC 的主要亚型之一,但目前用于 LUSC 诊断的生物标志物较少。本研究旨在探讨腺苷酸脱氨酶 RNA 特异性 B1(ADARB1)在肺鳞状细胞癌(LUSC)中的表达和作用。综合生物信息学分析用于确定 ADARB1 表达对 LUSC 发生和预后的影响。进一步通过免疫组织化学(IHC)检查 ADARB1 的表达。生物信息学分析表明 ADARB1 在 LUSC 中下调,作为一种潜在的肿瘤抑制因子,这一结果通过对肺癌组织芯片进行的 IHC 得到了验证。临床研究表明 ADARB1 的表达和甲基化水平与 LUSC 患者的特征显著相关。此外,与正常肺组织相比,LUSC 组织中 ADARB1 的全甲基化水平上调。cg24063645 的高甲基化水平与 LUSC 患者的总生存时间缩短相关。在 LUSC 中,ADARB1 与表皮生长因子受体(EGFR)的表达呈负相关。使用基因表达综合数据库,提示 ADARB1 在 LUSC 中的表达与肺腺癌显著不同。此外,还进行了蛋白质-蛋白质相互作用研究和生物学过程注释分析。本研究表明 ADARB1 在 LUSC 中下调;因此,ADARB1 可能作为 LUSC 的特异性生物标志物和潜在的治疗靶点。

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