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与肌层浸润性膀胱癌发生相关的预后相关基因的鉴定及免疫相关性

Identification and Immunocorrelation of Prognosis-Related Genes Associated With Development of Muscle-Invasive Bladder Cancer.

作者信息

Li Jingxian, Lou Yantao, Li Shuai, Sheng Fei, Liu Shuaibing, Du E, Zhang Zhihong

机构信息

Tianjin Institute of Urology, The Second Hospital of Tianjin Medical University, Tianjin, China.

Tianjin Hospital, The Tianjin Medical University, Tianjin, China.

出版信息

Front Mol Biosci. 2021 Jan 29;7:598599. doi: 10.3389/fmolb.2020.598599. eCollection 2020.

DOI:10.3389/fmolb.2020.598599
PMID:33604353
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7884823/
Abstract

Improved understanding of the molecular mechanisms and immunoregulation of muscle-invasive bladder cancer (MIBC) is essential to predict prognosis and develop new targets for therapies. In this study, we used the cancer genome atlas (TCGA) MIBC and GSE13507 datasets to explore the differential co-expression genes in MIBC comparing with adjacent non-carcinoma tissues. We firstly screened 106 signature genes by Weighted Gene Co-expression Network Analysis (WGCNA) and further identified 15 prognosis-related genes of MIBC using the univariate Cox progression analysis. Then we systematically analyzed the genetic alteration, molecular mechanism, and clinical relevance of these 15 genes. We found a different expression alteration of 15 genes in MIBC comparing with adjacent non-carcinoma tissues and normal tissues. Meanwhile, the biological functions and molecular mechanisms of them were also discrepant. Among these, we observed the ANLN was highly correlated with multiple cancer pathways, molecular function, and cell components, revealing ANLN may play a pivotal role in MIBC development. Next, we performed a consensus clustering of 15 prognosis-related genes; the results showed that the prognosis, immune infiltration status, stage, and grade of MIBC patients were significantly different in cluster1/2. We further identified eight-genes risk signatures using the least absolute shrinkage and selection operator (LASSO) regression analysis based on the expression values of 15 prognosis-related genes, and also found a significant difference in the prognosis, immune infiltration status, stage, grade, and age in high/low-risk cohort. Moreover, the expression of PD-1, PD-L1, and CTLA4 was significantly up-regulated in cluster1/high-risk-cohort than that in cluster2/low-risk-cohort. High normalized enrichment score of the Mitotic spindle, mTORC1, Complement, and Apical junction pathway suggested that they might be involved in the distinct tumor immune microenvironment (TIME) of cluster1/2 and high-/low-risk-cohort. Our study identified 15 prognosis-related genes of MIBC, provided a feasible stratification method to help for the future immunotherapy strategies of MIBC patients.

摘要

深入了解肌层浸润性膀胱癌（MIBC）的分子机制和免疫调节对于预测预后和开发新的治疗靶点至关重要。在本研究中，我们使用癌症基因组图谱（TCGA）的MIBC数据集和GSE13507数据集，探索MIBC与相邻非癌组织相比的差异共表达基因。我们首先通过加权基因共表达网络分析（WGCNA）筛选出106个特征基因，并使用单变量Cox进展分析进一步鉴定出15个MIBC的预后相关基因。然后，我们系统地分析了这15个基因的基因改变、分子机制和临床相关性。我们发现与相邻非癌组织和正常组织相比，MIBC中15个基因存在不同的表达改变。同时，它们的生物学功能和分子机制也存在差异。其中，我们观察到ANLN与多种癌症途径、分子功能和细胞成分高度相关，表明ANLN可能在MIBC的发生发展中起关键作用。接下来，我们对15个预后相关基因进行了一致性聚类；结果显示，MIBC患者在cluster1/2中的预后、免疫浸润状态、分期和分级存在显著差异。我们基于15个预后相关基因的表达值，使用最小绝对收缩和选择算子（LASSO）回归分析进一步鉴定出8基因风险特征，并且还发现高/低风险队列在预后、免疫浸润状态、分期、分级和年龄方面存在显著差异。此外，与cluster2/低风险队列相比，cluster1/高风险队列中PD-1、PD-L1和CTLA4的表达显著上调。有丝分裂纺锤体、mTORC1、补体和顶端连接途径的高标准化富集分数表明，它们可能参与了cluster1/2和高/低风险队列不同的肿瘤免疫微环境（TIME）。我们的研究鉴定出15个MIBC的预后相关基因，提供了一种可行的分层方法，有助于未来MIBC患者的免疫治疗策略。

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and in Muscle Invasive Bladder Cancer: A Functional and Clinical Evaluation Based on In Silico and In Vitro Data.以及在肌肉浸润性膀胱癌中：基于计算机模拟和体外数据的功能与临床评估
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The global burden of urinary bladder cancer: an update.全球膀胱癌负担：更新。
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