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一个与吸烟相关的 5-长链非编码 RNA 特征可预测肌层浸润性膀胱癌患者的总生存。

A 5-lncRNA Signature Associated with Smoking Predicts the Overall Survival of Patients with Muscle-Invasive Bladder Cancer.

机构信息

Department of Oncology, Shanghai Medical College, Fudan University, China.

Department of Urology, Fudan University Shanghai Cancer Center, China.

出版信息

Dis Markers. 2021 Jan 18;2021:8839747. doi: 10.1155/2021/8839747. eCollection 2021.

Abstract

Increasing evidence demonstrated that noncoding RNA is abnormally expressed in cancer tissues and serves a vital role in tumorigenesis, tumor development, and metastasis. The aim of the present study was to determine an lncRNA signature in order to predict the overall survival (OS) of patients with muscle-invasive bladder cancer (MIBC). A total of 246 patients with pathologically confirmed MIBC in The Cancer Genome Atlas (TCGA) dataset were recruited and included in the present study. We choose patients who have smoked less (including never smoking) or more than 15 years. A total of 44 differentially expressed lncRNAs were identified with a fold change larger than 1.5 and a value < 0.05 through the limma package. Subsequently, a comparison between patients with no tobacco smoke exposure for <15 years and patients who had been exposed to tobacco smoke for >15 years was performed by using the matchIt package. Among the 44 differentially expressed lncRNAs, 5 lncRNAs were identified to be significantly associated with OS. Based on the characteristic risk scores of these 5 lncRNAs, patients were divided into low-risk and high-risk groups and exhibited significant differences in OS. Multivariate Cox regression analysis demonstrated that the 5-lncRNA signature was independent of age, tumor-node metastasis (TNM) staging, lymphatic node status, and adjuvant postoperative radiotherapy. In the present study, a novel 5-lncRNA signature was developed and was demonstrated to be useful in predicting the survival of patients with MIBC. If validated, this lncRNA signature may assist in the selection of a high-risk subpopulation that requires more aggressive therapeutic intervention. The risk scores involved in several associated pathways were identified using gene set enrichment analysis (GSEA). However, the clinical implications and mechanism of these 5 lncRNAs require further investigation.

摘要

越来越多的证据表明,非编码 RNA 在癌症组织中异常表达,并在肿瘤发生、肿瘤发展和转移中发挥重要作用。本研究旨在确定一个 lncRNA 特征,以预测肌层浸润性膀胱癌(MIBC)患者的总生存期(OS)。本研究共纳入了癌症基因组图谱(TCGA)数据库中 246 例经病理证实的 MIBC 患者。我们选择吸烟时间少于 15 年(包括从不吸烟)或吸烟时间超过 15 年的患者。通过 limma 包,我们发现了 44 个差异表达的 lncRNA,其 fold change 大于 1.5, 值<0.05。随后,通过 matchIt 包对吸烟时间少于 15 年和吸烟时间超过 15 年的患者进行比较。在 44 个差异表达的 lncRNA 中,有 5 个 lncRNA 与 OS 显著相关。基于这 5 个 lncRNA 的特征风险评分,患者被分为低风险组和高风险组,两组的 OS 存在显著差异。多因素 Cox 回归分析表明,5-lncRNA 特征独立于年龄、肿瘤-淋巴结转移(TNM)分期、淋巴结状态和辅助术后放疗。在本研究中,开发了一个新的 5-lncRNA 特征,用于预测 MIBC 患者的生存情况。如果得到验证,该 lncRNA 特征可能有助于选择需要更积极治疗干预的高危亚群。使用基因集富集分析(GSEA)确定了与几个相关通路相关的风险评分。然而,这些 5 个 lncRNA 的临床意义和机制需要进一步研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/707d/7914096/67eb35d17eed/DM2021-8839747.001.jpg

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