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European Journal of Medical Research

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Open Access 01-12-2024 | Research

TFRC, associated with hypoxia and immune, is a prognostic factor and potential therapeutic target for bladder cancer

Authors: Runhua Tang, Haoran Wang, Jianyong Liu, Liuqi Song, Huimin Hou, Ming Liu, Jianye Wang, Jianlong Wang

Published in: European Journal of Medical Research | Issue 1/2024

Abstract

Background

Bladder cancer is a common malignancy of the urinary system, and the survival rate and recurrence rate of patients with muscular aggressive (MIBC) bladder cancer are not ideal. Hypoxia is a pathological process in which cells acquire special characteristics to adapt to anoxic environment, which can directly affect the proliferation, invasion and immune response of bladder cancer cells. Understanding the exact effects of hypoxia and immune-related genes in BLCA is helpful for early assessment of the prognosis of BLCA. However, the prognostic model of BLCA based on hypoxia and immune-related genes has not been reported.

Purpose

Hypoxia and immune cell have important role in the prognosis of bladder cancer (BLCA). The aim of this study was to investigate whether hypoxia and immune related genes could be a novel tools to predict the overall survival and immunotherapy of BLCA patients.

Methods

First, we downloaded transcriptomic data and clinical information of BLCA patients from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. A combined hypoxia and immune signature was then constructed on the basis of the training cohort via least absolute shrinkage and selection operator (LASSO) analysis and validated in test cohort. Afterwards, Kaplan–Meier curves, univariate and multivariate Cox and subgroup analysis were employed to assess the accuracy of our signature. Immune cell infiltration, checkpoint and the Tumor Immune Dysfunction and Exclusion (TIDE) algorithm were used to investigate the immune environment and immunotherapy of BLCA patients. Furthermore, we confirmed the role of TFRC in bladder cancer cell lines T24 and UMUC-3 through cell experiments.

Results

A combined hypoxia and immune signature containing 8 genes were successfully established. High-risk group in both training and test cohorts had significantly poorer OS than low-risk group. Univariate and multivariate Cox analysis indicated our signature could be regarded as an independent prognostic factor. Different checkpoint was differently expressed between two groups, including CTLA4, HAVCR2, LAG3, PD-L1 and PDCD1. TIDE analysis indicated high-risk patients had poor response to immunotherapy and easier to have immune escape. The drug sensitivity analysis showed that high-risk group patients were more potentially sensitive to many drugs. Meanwhile, TFRC could inhibit the proliferation and invasion ability of T24 and UMUC-3 cells.

Conclusion

A combined hypoxia and immune-related gene could be a novel predictive model for OS and immunotherapy estimation of BLCA patients and TFRC could be used as a potential therapeutic target in the future.

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Title: TFRC, associated with hypoxia and immune, is a prognostic factor and potential therapeutic target for bladder cancer
Authors: Runhua Tang
Haoran Wang
Jianyong Liu
Liuqi Song
Huimin Hou
Ming Liu
Jianye Wang
Jianlong Wang
Publication date: 01-12-2024
Publisher: BioMed Central
Published in: European Journal of Medical Research / Issue 1/2024
Electronic ISSN: 2047-783X
DOI: https://doi.org/10.1186/s40001-024-01688-9

Keynote webinar | Spotlight on medication adherence

Springer Medicine

TFRC, associated with hypoxia and immune, is a prognostic factor and potential therapeutic target for bladder cancer

Abstract

Background

Purpose

Methods

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Purpose

Methods

Results

Conclusion

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