APOBEC-mediated mutagenesis is a favorable predictor of prognosis and immunotherapy for bladder cancer patients: evidence from pan-cancer analysis and multiple databases

The APOBEC (apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like) family-mediated mutagenesis is widespread in human cancers. However, our knowledge of the biological feature and clinical relevance of APOBECs and APOBEC mutagenesis in cancers remains limited. In this study, with a series...

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Bibliographic Details
Published in:Theranostics 2022-01, Vol.12 (9), p.4181-4199
Main Authors: Shi, Run, Wang, Xin, Wu, Yang, Xu, Bin, Zhao, Tianyu, Trapp, Christian, Wang, Xuanbin, Unger, Kristian, Zhou, Cheng, Lu, Shun, Buchner, Alexander, Schulz, Gerald Bastian, Cao, Fengjun, Belka, Claus, Su, Chuan, Li, Minglun, Shu, Yongqian
Format: Article
Language:English
Subjects:
Algorithms
Bladder cancer
Evolution
Gene expression
Genomes
Genomics
Immunotherapy
Medical prognosis
Mutagenesis
Mutation
Research Paper
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Summary:The APOBEC (apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like) family-mediated mutagenesis is widespread in human cancers. However, our knowledge of the biological feature and clinical relevance of APOBECs and APOBEC mutagenesis in cancers remains limited. In this study, with a series of bioinformatic and statistical approaches, we performed a comprehensive analysis of multiple levels of data, including whole-exome sequencing (WES) and targeted next-generation sequencing (NGS), transcriptome (bulk RNA-seq and single-cell RNA-seq), immune signatures and immune checkpoint blockade (ICB) potential, patient survival and drug sensitivity, to reveal the distribution characteristics and clinical significance of APOBECs and APOBEC mutagenesis in pan-cancer especially bladder cancer (BLCA). APOBEC mutagenesis dominates in the mutational patterns of BLCA. A higher enrichment score of APOBEC mutagenesis correlates with favorable prognosis, immune activation and potential ICB response in BLCA patients. APOBEC3A and 3B play a significant role in the malignant progression and cell differentiation within the tumor microenvironment. Furthermore, using machine learning approaches, a prognostic APOBEC mutagenesis-related model was established and validated in different BLCA cohorts. Our study illustrates the characterization of APOBECs and APOBEC mutagenesis in multiple cancer types and highlights its potential value as a promising biomarker for prognosis and immunotherapy in BLCA.
ISSN:1838-7640
1838-7640
DOI:10.7150/thno.73235