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

TL;DR

APOBEC mutagenesis is linked to better outcomes and immunotherapy response in bladder cancer patients, based on analysis of multiple cancer datasets.

Contribution

The study identifies APOBEC mutagenesis as a favorable biomarker for prognosis and immunotherapy in bladder cancer using pan-cancer and multi-omics data.

Findings

APOBEC mutagenesis is a dominant mutational pattern in bladder cancer.

Higher APOBEC enrichment correlates with better prognosis and immune activation in bladder cancer patients.

APOBEC3A and APOBEC3B are key in tumor progression and immune response in the tumor microenvironment.

Abstract

Background: 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.

Methods: 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).

Results: 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.

Conclusions: 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.

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