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

Theranostics. 2022 May 16;12(9):4181-4199. doi: 10.7150/thno.73235. eCollection 2022.


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.

Keywords: APOBEC mutagenesis; Immunotherapy; Pan-cancer analysis; Prognosis.

MeSH terms

  • Cytidine Deaminase / genetics
  • Humans
  • Immunotherapy
  • Mutagenesis
  • Proteins
  • Tumor Microenvironment
  • Urinary Bladder Neoplasms* / genetics
  • Urinary Bladder Neoplasms* / pathology
  • Urinary Bladder Neoplasms* / therapy


  • Proteins
  • APOBEC3A protein, human
  • Cytidine Deaminase