Bladder cancer-derived exosomal KRT6B promotes invasion and metastasis by inducing EMT and regulating the immune microenvironment

Background 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-encapsulat...

Full description

Saved in:
Bibliographic Details
Published in:Journal of translational medicine 2022-07, Vol.20 (1), p.1-308, Article 308
Main Authors: Song, Qiang, Yu, Hao, Cheng, Yidong, Han, Jie, Li, Kai, Zhuang, Juntao, Lv, Qiang, Yang, Xiao, Yang, Haiwei
Format: Article
Language:English
Subjects:
Analysis
Angiogenesis
Antibodies
Bladder cancer
Cancer
Care and treatment
Correlation analysis
Datasets
Diagnosis
Drug resistance
Epithelial–mesenchymal transition
Exosome
Exosomes
Gene expression
Genetic aspects
Genomes
Genomics
Immune response
krt6b
Mesenchyme
Metastases
Metastasis
Microenvironments
Prevention
Prognosis marker
Proteins
Risk factors
Software
Statistical analysis
Survival
Survival analysis
Therapeutic targets
Tumor microenvironment
Tumorigenesis
Tumors
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Background 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. Methods 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. Results 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. Conclusion 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. Keywords: Bladder cancer, Exosome, krt6b, Epithelial-mesenchymal transition, Immune response, Prognosis marker
ISSN:1479-5876
1479-5876
DOI:10.1186/s12967-022-03508-2