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

作者：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^*

来源：2022, 12(9): 4181-4199.

DOI：10.7150/thno.73235

• APOBEC mutagenesis
• Pan-cancer analysis
• Immunotherapy
• Prognosis

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.

• 单位
  上海交通大学; 1; 南方医科大学; 电子科技大学