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通过创新预测模型识别糖代谢相关长链非编码RNA作为膀胱癌的预后标志物

Recognition of Glycometabolism-Associated lncRNAs as Prognosis Markers for Bladder Cancer by an Innovative Prediction Model.

作者信息

Tang Dongdong, Li Yangyang, Tang Ying, Zheng Haoxiang, Luo Weihan, Li Yuqing, Li Yingrui, Wang Zhiping, Wu Song

机构信息

Department of Urology, Lanzhou University Second Hospital, Lanzhou, China.

Institute of Urology, The Third Affiliated Hospital of Shenzhen University (Luohu Hospital Group), Shenzhen University, Shenzhen, China.

出版信息

Front Genet. 2022 Jul 19;13:918705. doi: 10.3389/fgene.2022.918705. eCollection 2022.

Abstract

The alteration of glycometabolism is a characteristic of cancer cells. Long non-coding RNAs (lncRNAs) have been documented to occupy a considerable position in glycometabolism regulation. This research aims to construct an effective prediction model for the prognosis of bladder cancer (BC) based on glycometabolism-associated lncRNAs (glyco-lncRNAs). Pearson correlation analysis was applied to get glyco-lncRNAs, and then, univariate cox regression analysis was employed to further filtrate survival time-associated glyco-lncRNAs. Multivariate cox regression analysis was utilized to construct the prediction model to divide bladder cancer (BC) patients into high- and low-risk groups. The overall survival (OS) rates of these two groups were analyzed using the Kaplan-Meier method. Next, gene set enrichment analysis and Cibersortx were used to explore the enrichment and the difference in immune cell infiltration, respectively. pRRophetic algorithm was applied to explore the relation between chemotherapy sensitivity and the prediction model. Furthermore, reverse transcriptase quantitative polymerase chain reaction was adopted to detect the lncRNAs constituting the prediction signature in tissues and urine exosomal samples of BC patients. A powerful model including 6 glyco-lncRNAs was proposed, capable of suggesting a risk score for each BC patient to predict prognosis. Patients with high-risk scores demonstrated a shorter survival time both in the training cohort and testing cohort, and the risk score could predict the prognosis without depending on the traditional clinical traits. The area under the receiver operating characteristic curve of the risk score was higher than that of other clinical traits (0.755 > 0.640, 0.485, 0.644, or 0.568). The high- and low-risk groups demonstrated very distinct immune cells infiltration conditions and gene set enriched terms. Besides, the high-risk group was more sensitive to cisplatin, docetaxel, and sunitinib. The expression of lncRNA AL354919.2 featured with an increase in low-grade patients and a decrease in T3-4 and Stage III-IV patients. Based on the experiment results, lncRNA AL355353.1, AC011468.1, and AL354919.2 were significantly upregulated in tumor tissues. This research furnishes a novel reference for predicting the prognosis of BC patients, assisting clinicians with help in the choice of treatment.

摘要

糖代谢改变是癌细胞的一个特征。长链非编码RNA(lncRNAs)已被证明在糖代谢调节中占据相当重要的地位。本研究旨在基于糖代谢相关lncRNAs(糖基化lncRNAs)构建一种有效的膀胱癌(BC)预后预测模型。应用Pearson相关分析来获取糖基化lncRNAs,然后采用单因素cox回归分析进一步筛选与生存时间相关的糖基化lncRNAs。利用多因素cox回归分析构建预测模型,将膀胱癌(BC)患者分为高风险组和低风险组。使用Kaplan-Meier方法分析这两组的总生存率(OS)。接下来,分别使用基因集富集分析和Cibersortx来探索免疫细胞浸润的富集情况和差异。应用pRRophetic算法来探索化疗敏感性与预测模型之间的关系。此外,采用逆转录定量聚合酶链反应检测BC患者组织和尿液外泌体样本中构成预测特征的lncRNAs。提出了一个包含6个糖基化lncRNAs的强大模型,能够为每个BC患者给出一个风险评分以预测预后。高风险评分的患者在训练队列和测试队列中的生存时间均较短,且风险评分可以独立于传统临床特征预测预后。风险评分的受试者工作特征曲线下面积高于其他临床特征(0.755 > 0.640、0.485、0.644或0.568)。高风险组和低风险组表现出非常不同的免疫细胞浸润情况和基因集富集术语。此外,高风险组对顺铂、多西他赛和舒尼替尼更敏感。lncRNA AL354919.2的表达在低级别患者中升高,在T3-4期和III-IV期患者中降低。基于实验结果,lncRNA AL355353.1、AC011468.1和AL354919.2在肿瘤组织中显著上调。本研究为预测BC患者的预后提供了新的参考,有助于临床医生选择治疗方案。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ee93/9343799/e396eef362fc/fgene-13-918705-g001.jpg

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