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Open Access 01-12-2022 | Insulins | Primary research

Comprehensive analysis of N⁶-methyladenosine regulators with the tumor immune landscape and correlation between the insulin-like growth factor 2 mRNA-binding protein 3 and programmed death ligand 1 in bladder cancer

Authors: Jianfeng Cui, Yaofeng Zhu, Xiaochen Liu, Wenfu Wang, Xuewen Jiang, Yangyang Xia, Guanwen Zhou, Shouzhen Chen, Benkang Shi

Published in: Cancer Cell International | Issue 1/2022

Abstract

Background

N⁶-methyladenosine (m⁶A) is one of the most abundant post-transcriptional modifications of RNA. However, there is limited information about the potential roles of m⁶A regulators in tumor immunity. Therefore, in this study, we aimed to testify the functions of m⁶A regulators in bladder cancer as well as their association with the tumor immune landscape.

Methods

We reported the variation and expression levels of m6A regulators in the TCGA database and GTEx database of bladder cancer. Clusters, risk score patterns, and nomograms were constructed to evaluate the function and prognostic value of m⁶A regulators. Furthermore, we constructed nomogram to evaluate the prognosis of the individual patients. The correlation between insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) and programmed cell death ligand 1 (PD-L1) was evaluated both in vitro and in vivo.

Results

We found that the tumor grade and DNA damage pathways were strongly correlated with distinct clusters. Furthermore, two risk score groups with six m⁶A regulators were identified using the least absolute shrinkage and selection operator (LASSO) and multivariable Cox regression analysis, which could be regarded as independent prognostic markers in patients with bladder cancer. The risk score pattern was linked to the tumor immune landscape, indicating a correlation between immune checkpoints and m⁶A regulators. Moreover, an m⁶A regulator, IGF2BP3, was found to be highly expressed in the tumor samples, regulating both the total and membrane-bound PD-L1 expression levels.

Conclusions

The results of this study revealed that the m⁶A clusters and patterns play crucial roles in the regulation of tumor immunity, which may be used to develop comprehensive treatment strategies for the management of bladder cancer.

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Title: Comprehensive analysis of N6-methyladenosine regulators with the tumor immune landscape and correlation between the insulin-like growth factor 2 mRNA-binding protein 3 and programmed death ligand 1 in bladder cancer
Authors: Jianfeng Cui
Yaofeng Zhu
Xiaochen Liu
Wenfu Wang
Xuewen Jiang
Yangyang Xia
Guanwen Zhou
Shouzhen Chen
Benkang Shi
Publication date: 01-12-2022
Publisher: BioMed Central
Keywords: Insulins
Insulins
Published in: Cancer Cell International / Issue 1/2022
Electronic ISSN: 1475-2867
DOI: https://doi.org/10.1186/s12935-022-02456-7

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