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鉴定和验证七个 RNA 结合蛋白基因作为口腔鳞状细胞癌的预后标志物。

Identification and validation of seven RNA binding protein genes as a prognostic signature in oral cavity squamous cell carcinoma.

机构信息

Hospital of Stomatology, Guanghua School of Stomatology, Guangdong Province Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou, Guangdong, China.

Department of Oral and Maxillofacial Surgery, Sun Yat-sen Memorial Hospital of Sun Yat-Sen University, Guangzhou China.

出版信息

Bioengineered. 2021 Dec;12(1):7248-7262. doi: 10.1080/21655979.2021.1974328.

Abstract

RNA binding proteins (RBPs) play a pivotal role in various biological processes, and aberrant expression of RBPs is closely associated with tumorigenesis and progression. However, the role of RBPs in oral cavity squamous cell carcinoma (OCSCC) is yet unveiled. In this study, RNA sequences and clinical information of OCSCC samples were acquired from The Cancer Genome Atlas (TCGA) database. A total of 650 RBPs, with significantly different expression between healthy and OCSCC samples, were identified using the limma package. A prognostic model was constructed by Lasso-Cox analysis, resulting in the determination of 7 prognosis-related RBPs: ERMP1, RNASE3, ARL4D, CSRP2, ULK1, ZC3H12D, and RPS28. Based on the prognostic model, the risk scores of the OCSCC samples were calculated. The capability of the prognostic model was further evaluated using the receiver operating characteristic curve (ROC). The areas under ROC were 0.764, 0.771, and 0.809 at 1, 3 and 5-year respectively in the TCGA dataset. Internal and external validation showed satisfactory predictive capability for prognosis in OCSCC. In addition, a nomogram was created to graphically present the model. To further validate the analytical data, qRT-PCR was performed on normal and OCSCC cell lines. The mRNA expression of the 7 prognostic genes was in accordance with the analytical results. Functional analysis and gene connection networks were used to describe the biological functions and underlying interactions among the 7 prognostic genes Overall, 7 prognosis-related RBPs were identified, which could be used to predict clinical prognosis and to identify potential therapeutic targets for OCSCC.

摘要

RNA 结合蛋白 (RBPs) 在各种生物过程中发挥着关键作用,并且 RBP 的异常表达与肿瘤发生和进展密切相关。然而,RBPs 在口腔鳞状细胞癌 (OCSCC) 中的作用尚未揭示。在这项研究中,从癌症基因组图谱 (TCGA) 数据库中获取了 OCSCC 样本的 RNA 序列和临床信息。使用 limma 包鉴定了 650 个在健康和 OCSCC 样本之间表达差异显著的 RBP。通过 Lasso-Cox 分析构建了预后模型,确定了 7 个与预后相关的 RBP:ERMP1、RNASE3、ARLD、CSRP2、ULK1、ZC3H12D 和 RPS28。基于预后模型,计算了 OCSCC 样本的风险评分。使用接收器操作特征曲线 (ROC) 进一步评估了预后模型的能力。在 TCGA 数据集,ROC 的 AUC 在 1、3 和 5 年时分别为 0.764、0.771 和 0.809。内部和外部验证显示了该模型对 OCSCC 预后的良好预测能力。此外,还创建了一个列线图来直观地呈现模型。为了进一步验证分析数据,对正常和 OCSCC 细胞系进行了 qRT-PCR。7 个预后基因的 mRNA 表达与分析结果一致。功能分析和基因连接网络用于描述 7 个预后基因之间的生物学功能和潜在相互作用。总之,确定了 7 个与预后相关的 RBP,可用于预测临床预后,并为 OCSCC 识别潜在的治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/099c/8806873/d6c3526a96f8/KBIE_A_1974328_F0001_B.jpg

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