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

Cancer Cell International

Benkang Shi¹  Jianfeng Cui¹  Shouzhen Chen¹  Xuewen Jiang¹  Wenfu Wang¹  Yangyang Xia¹  Guanwen Zhou¹  Yaofeng Zhu¹  Xiaochen Liu² 

[1] Department of Urology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, 250012, Jinan, Shandong, China;Key Laboratory of Urinary Precision Diagnosis and Treatment in Universities of Shandong, 250012, Jinan, Shandong, China;The Key Laboratory of Experimental Teratology, Ministry of Education and Department of Molecular Medicine and Genetics, School of Basic Medical Sciences, Shandong University, 250012, Jinan, Shandong, China;

关键词: mA;    Immune landscape;    Bladder cancer;    IGF2BP3;    PD-L1;   

DOI  :  10.1186/s12935-022-02456-7

来源: Springer

【 摘 要 】

BackgroundN6-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.MethodsWe 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.ResultsWe 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.ConclusionsThe 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.

【 授权许可】

CC BY