IMR Press / FBL / Volume 28 / Issue 8 / DOI: 10.31083/j.fbl2808189
Open Access Original Research
RBP7 Regulated by EBF1 Affects Th2 Cells and the Oocyte Meiosis Pathway in Bone Metastases of Bladder Urothelial Carcinoma
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1 Department of Orthopaedics, The First Affiliated Hospital of Zhengzhou University, 450052 Zhengzhou, Henan, China
2 Department of Urology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200092, China
3 Shanghai Jiao Tong University School of Medicine, 200025 Shanghai, China
4 Tongji University School of Medicine, Tongji University, 200092 Shanghai, China
5 Department of Orthopedics, Naval Medical Center of PLA, Second Military Medical University, 200052 Shanghai, China
6 Division of Spine, Department of Orthopedics, Tongji Hospital affiliated to Tongji University School of Medicine, 200065 Shanghai, China
7 Department of Burn Surgery, The First Aliated Hospital of Naval Medical University, 200433, Shanghai, China
8 Research Unit of Key Techniques for Treatment of Burns and Combined Burns and Trauma Injury, Chinese Academy of Medical Sciences, 100007, Beijing, China
9 Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, 201204 Shanghai, China
*Correspondence: runzhihuang2022@163.com (Runzhi Huang); jiezhang@tongji.edu.cn (Jie Zhang); gzhuangzq@163.com (Zongqiang Huang)
These authors contributed equally.
Front. Biosci. (Landmark Ed) 2023, 28(8), 189; https://doi.org/10.31083/j.fbl2808189
Submitted: 12 July 2022 | Revised: 12 January 2023 | Accepted: 2 February 2023 | Published: 31 August 2023
Copyright: © 2023 The Author(s). Published by IMR Press.
This is an open access article under the CC BY 4.0 license.
Abstract

Background: Bladder urothelial carcinoma (BLCA) is a malignancy with a high incidence worldwide. One-third of patients may experience aggressive progression later on, and 70% of patients who have undergone surgical intervention will still suffer from metastasis. Materials and Methods: RNA sequencing profiles of BLCA samples were obtained from The Cancer Genome Atlas (TCGA) database. Differential expression and univariate Cox regression analyses were performed to identify prognosis-related differentially expressed immune genes (DEIGs). Subsequently, a proportional hazards model of DEIGs was then constructed by univariate regression analysis. Differential expression and correlation analyses, CIBERSORT, Single Sample Gene Set Enrichment Analysis (ssGSEA), GSVA were conducted on transcription factors (TFs), immune cells/pathways and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. The regulation network was then constructed. Eventually, ATAC-seq, ChIP-seq, scRNA-seq, and multiple online databases were employed for further validation. Results: A proportional hazards model of 31 DEIGs was constructed and risk score was calculated and proven to be a independent prognostic factor. Then 5 immune genes were characterized to be significantly correlated with bone metastasis, stage and TF expression simultaneously. 4 TFs were identified to be significantly correlated with prognosis and RBP7 expression. 5 immune cells/pathways were revealed to be significantly correlated with RBP7 expression. Only 1 KEGG pathway was identified to be significant in Gene Set Enrichment Analysis (GSEA) and Gene Set Variation Analysis (GSVA) analyses. The regulatory relationship was then constructed, in which the correlation between EBF1 and RBP7 (R = 0.677, p < 0.001), Th2 cells and RBP7 (R = 0.23, p < 0.001), the oocyte meiosis pathway and RBP7 (R = 0.14, p = 0.042) were the most statistically significant. The results were further confirmed by Assay for Transposase Accessible Chromatin with high-throughput sequencing (ATAC-seq), Chromatin Immunoprecipitation sequencing (ChIP-seq), single-cell RNA sequencing (scRNA-seq), and multiple online databases validation. Conclusions: This study revealed that the EBF1-RBP7 regulatory relationship had potential importance in the bone metastasis in BLCA through Th2 cells and the oocyte meiosis pathway.

Keywords
bladder urothelial carcinoma
bone metastasis
immune genes
biomarkers
retinol binding protein 7
Funding
23YF1458400/Shanghai Rising-Star Program (Sailing Special Program)
201940306/Shanghai Municipal Health Commission
201602031/Henan medical science and technology research project
SBGJ202002031/Key project of provincial and ministerial co-construction of Henan Medical Science and Technology
Figures
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