Table 1.

Beneficial and detrimental outcomes of the A3s in cancer.

beneficial outcomes

detrimental outcomes

—A3-mediated RNA editing is positively associated with elevated immune activity and improved survival in BRCA [22] —germline A3B deletion influence APOBEC mutational signature, neoantigen loads and relative immune cell compositions in BRCA that is beneficial for cancer immunotherapy [36] —A3B and APOBEC mutational signature is specifically enriched in patients with durable clinical benefit after immunotherapy in NSCLC [133] —increased APOBEC mutagenesis in BLCA patients have a significant positive association with neoantigen loads, the relative abundances of immune-related gene expression and the improved survival [36,134,135,192] —increased mutation loads, especially in DNA repair genes, were associated with responsiveness to neoadjuvant cisplatin-based treatment of MIBC [134] —hypermutation in BLCA (mainly by A3A) could contribute substantially to the success of immune therapies [4] —higher A3G expression sensitizes cells to cisplatin which likely contributes to the improved patient responses observed in HNSCC [231] —tumour-infiltrating lymphocytes in cervical cancer are more reactive to neoantigens than to HPV viral epitopes [235], and the abundance of those neoantigens could be associated with the deaminase activity of upregulated A3A and A3B expression —cervical infections with a greater burden of somatic HPV16 A3-induced mutations are more likely to be benign or subsequently clear [132]

—A3B overexpression is associated with adverse outcomes in ER+ BRCA [140,141] —A3B deletion increases the risk of BRCA [155,156] and increases tumour mutational burden [152] —APOBEC is a mutagenic source, fuelling cancer heterogeneity and subclonal diversification in lung adenocarcinoma, squamous cell carcinoma, BRCA, HNSCC and BLCA [172] —A3B upregulation is associated with poor NSCLC prognosis [34] —A3H Hap I may cause early clonal mutations in lung adenocarcinoma [5] —the loss of A3H Hap I activity through the K121E variant may benefit the lung cancer and be detrimental to the host [174] —the single nucleotide polymorphism, rs1014971, was associated with BLCA risk [134] —A3A expression associates with HPV16 genome integration and hypermutations in oropharyngeal cancers [219]