肿瘤来源的外泌体最近被证明参与不同癌症过程的形成和进展,包括肿瘤微环境重塑,血管生成,入侵,转移,和抗药性。然而,外泌体包裹的核酸和蛋白质在膀胱癌中的功能和机制尚不清楚.本研究旨在探讨肿瘤来源的外泌体在膀胱癌发生发展中的作用。
在这项研究中,从癌症基因组图谱(TCGA)数据库和两个独立的基因表达综合(GEO)数据集收集基因表达谱和临床信息。从ExoCarta数据库获得包封在膀胱癌衍生的外泌体中的核酸和蛋白质。基于这些数据库,分析了外泌体mRNA和蛋白质的表达模式以及匹配的临床病理特征。此外,我们进行了一系列实验以验证相关发现。
在TCGA数据中发现了总共7280个差异表达的mRNA,其中52个mRNAs被证实包裹在膀胱癌来源的外泌体中。基于UALCAN数据库的生存分析表明,在前10个上调和前10个下调的外泌体基因中,只有KRT6B的表达对膀胱癌患者的生存率有统计学意义.此外,临床相关分析显示,KRT6B水平升高与膀胱癌分期密切相关,grade,和转移状态。GSEA显示,KRT6B不仅参与上皮-间质转化相关途径,而且参与膀胱癌的免疫反应。最终,我们的实验结果也与生物信息学分析一致。
KRT6B,可以在膀胱癌来源的外泌体中检测到,在膀胱癌的上皮间质转化和免疫反应中起重要作用。进一步的研究将使其成为膀胱癌的潜在预后标志物和治疗靶标。
Tumour-derived exosomes have recently been shown to participate in the formation and progression of different cancer processes, including tumour microenvironment remodelling, angiogenesis, invasion, metastasis, and drug resistance. However, the function and mechanism of exosome-encapsulated nucleic acids and proteins in bladder cancer remain unclear. This study aimed to investigate the effects of tumour-derived exosomes on the tumorigenesis and development of bladder cancer.
In this study, gene expression profiles and clinical information were collected from The Cancer Genome Atlas (TCGA) database and two independent Gene Expression Omnibus (GEO) datasets. The nucleic acids and proteins encapsulated in bladder cancer-derived exosomes were obtained from the ExoCarta database. Based on these databases, the expression patterns of exosomal mRNAs and proteins and the matched clinicopathological characteristics were analysed. Furthermore, we carried out a series of experiments to verify the relevant findings.
A total of 7280 differentially expressed mRNAs were found in TCGA data, of which 52 mRNAs were shown to be encapsulated in bladder cancer-derived exosomes. Survival analysis based on the UALCAN database showed that among the top 10 upregulated and the top 10 downregulated exosomal genes, only the expression of
KRT6B had a statistically significant effect on the survival of bladder cancer patients. Additionally, clinical correlation analysis showed that the elevated level of
KRT6B was highly associated with bladder cancer stage, grade, and metastasis status. GSEA revealed that
KRT6B was involved not only in epithelial-mesenchymal transition-related pathways but also in the immune response in bladder cancer. Ultimately, our experimental results were also consistent with the bioinformatic analysis.
KRT6B, which can be detected in bladder cancer-derived exosomes, plays an important role in the epithelial-mesenchymal transition and immune responses in bladder cancer. Further research will enable its potentially prognostic marker and therapeutic target for bladder cancer.