A comprehensive analysis of FBN2 in bladder cancer: A risk factor and the tumour microenvironment influencer

IF 1.9 4区 生物学 Q4 CELL BIOLOGY IET Systems Biology Pub Date : 2023-06-19 DOI:10.1049/syb2.12067
Zechao Lu, Zeguang Lu, Yongchang Lai, Haobin Zhou, Zhibiao Li, Wanyan Cai, Zeyao Xu, Hongcheng Luo, Yushu Chen, Jianyu Li, Jishen Zhang, Zhaohui He, Fucai Tang
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Abstract

Bladder cancer (BLCA) is a common and difficult-to-manage disease worldwide. Most common type of BLCA is urothelial carcinoma (UC). Fibrillin 2 (FBN2) was first discovered while studying Marfan syndrome, and its encoded products are associated with elastin fibres. To date, the role of FBN2 in BLCA remains unclear. The authors first downloaded data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). The patients were divided into high FBN2 expression and low FBN2 expression groups, and the survival curve, clinical characteristics, tumour microenvironment (TME), and immune cell differences were analysed between the two groups. Then, the differentially expressed genes (DEGs) were filtered, and functional enrichment for DEGs was performed. Finally, chemotherapy drug susceptibility analysis based on the high and low FBN2 groups was conducted. The authors found upregulated expression of FBN2 in BLCA and proved that FBN2 could be an independent prognostic factor for BLCA. TME analysis showed that the expression of FBN2 affects several aspects of the TME. The upregulated expression of FBN2 was associated with a high stromal score, which may lead to immunosuppression and be detrimental to immunotherapy. In addition, the authors found that NK cells resting, macrophage M0 infiltration, and other phenomena of immune cell infiltration appeared in the high expression group of FBN2. The high expression of FBN2 was related to the high sensitivity of some chemotherapy drugs. The authors systematically investigated the effects and mechanisms of FBN2 on BLCA and provided a new understanding of the role of FBN2 as a risk factor and TME influencer in BLCA.

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膀胱癌中FBN2的综合分析:一个危险因素和肿瘤微环境影响者
膀胱癌(BLCA)是世界范围内常见且难以治疗的疾病。最常见的BLCA类型是尿路上皮癌(UC)。纤维蛋白2 (FBN2)是在研究马凡氏综合征时首次发现的,其编码产物与弹性蛋白纤维有关。迄今为止,FBN2在BLCA中的作用尚不清楚。作者首先从癌症基因组图谱(TCGA)和基因表达图谱(GEO)下载数据。将患者分为FBN2高表达组和FBN2低表达组,分析两组患者的生存曲线、临床特征、肿瘤微环境(TME)、免疫细胞差异。然后,对差异表达基因(differential expression genes, deg)进行过滤,并对其进行功能富集。最后,根据FBN2高、低组进行化疗药物敏感性分析。作者发现FBN2在BLCA中表达上调,证明FBN2可能是BLCA的独立预后因素。TME分析表明,FBN2的表达影响TME的几个方面。FBN2表达上调与高基质评分相关,可能导致免疫抑制,不利于免疫治疗。此外,作者发现FBN2高表达组出现NK细胞静息、巨噬细胞M0浸润等免疫细胞浸润现象。FBN2的高表达与部分化疗药物的高敏感性有关。作者系统地研究了FBN2在BLCA中的作用和机制,并对FBN2作为BLCA的危险因素和TME影响因素的作用有了新的认识。
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来源期刊
IET Systems Biology
IET Systems Biology 生物-数学与计算生物学
CiteScore
4.20
自引率
4.30%
发文量
17
审稿时长
>12 weeks
期刊介绍: IET Systems Biology covers intra- and inter-cellular dynamics, using systems- and signal-oriented approaches. Papers that analyse genomic data in order to identify variables and basic relationships between them are considered if the results provide a basis for mathematical modelling and simulation of cellular dynamics. Manuscripts on molecular and cell biological studies are encouraged if the aim is a systems approach to dynamic interactions within and between cells. The scope includes the following topics: Genomics, transcriptomics, proteomics, metabolomics, cells, tissue and the physiome; molecular and cellular interaction, gene, cell and protein function; networks and pathways; metabolism and cell signalling; dynamics, regulation and control; systems, signals, and information; experimental data analysis; mathematical modelling, simulation and theoretical analysis; biological modelling, simulation, prediction and control; methodologies, databases, tools and algorithms for modelling and simulation; modelling, analysis and control of biological networks; synthetic biology and bioengineering based on systems biology.
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