Table 5 Association of APOBEC3 expression and APOBEC3-induced mutations with clinical outcomes by cancer type
From: APOBEC3-mediated mutagenesis in cancer: causes, clinical significance and therapeutic potential
Cancer type | APOBEC3(s)* | Outcome type | Immunotherapy context? | Clinical outcome | References |
|---|---|---|---|---|---|
Adrenal | 3B | Adverse | No | Shorter overall and disease-free survival | [44] |
Bladder | 3B | Positive | No | Longer survival with APOBEC3B-enhancing SNP (rs101497) | [61] |
Mutation burden | Positive | No | Longer survival in muscle-invasive disease cohort | [170] | |
Mutation burden | Positive | No | Longer survival | [46] | |
3D and 3H | Positive | No | Better overall survival | [171] | |
3B | Adverse | No | Shorter progression-free survival with mutagenic A3B1 isoform | [1] | |
Mutation burden | Adverse | No | Higher risk of class 2a tumors and poor outcomes for non-muscle invasive disease | [172] | |
3A and 3B | Adverse | No | Increased risk of class 2a tumors | [173] | |
Mutation burden | Positive | Yes | Longer survival overall and better response to immune checkpoint blockade therapy | [160] | |
Mutation burden | Positive | Yes | Increased responsiveness to immunotherapy | [174] | |
Breast | 3A | Adverse | No | Advanced tumor stage, higher histological grade, and more lymph node involvement | [64] |
3A | Adverse | No | Shorter overall survival | [175] | |
3B | Adverse | No | Higher tumor grade with lymph node involvement and worse prognosis | [105] | |
3B | Adverse | No | Higher nuclear grade and more frequent lymph node metastasis | [176] | |
3B | Adverse | No | Shorter disease-free, metastasis-free, and overall survival. Lower overall survival in ER+ subgroup | [177] | |
3B | Adverse | No | Shorter survival in ER+ but not ER- group | [161] | |
3B | Adverse | No | Lower recurrence-free survival in a combined analysis and ER+ subgroup | [178] | |
3A/B | Adverse | No | Higher histological grade with 3A/B chimera | [64] | |
3A-H | Mixed | No | Aggressive pathology and shorter survival (3A and 3B). Improved survival (3C-H) | [48] | |
3B | Mixed | No | Shorter replace-free, metastasis-free, and overall survival (mRNA). Increased disease-free survival (protein) | [165] | |
3B | Mixed | No | Higher nuclear grade and Ki-67 labeling index, but improved responsiveness to neoadjuvant chemotherapy | [179] | |
Mutation burden | Adverse (overall) | Yes | Shorter survival with first-line endocrine and CDK4/6i therapy, but improved response to immune checkpoint blockade therapy | [180] | |
Positive (immunotherapy) | |||||
Mutation burden | Positive | Yes | Improved response to immunotherapy | [181] | |
Esophageal | 3B | Adverse/none | No | Higher histological grade | [39] |
Gastric | 3B | Adverse (overall) | No | Shorter overall and progression-free survival, but improved response to fluorouracil-based adjuvant chemotherapy and PD-1 blockade therapy | [37] |
Positive (immunotherapy) | Yes | ||||
3B | Adverse | No | Aggressive pathology and poor survival | [38] | |
Glioma | 3B, 3C, 3D, 3F, 3G, 3H | Adverse | No | Poor prognosis, especially in the low-grade subtype | [51] |
Head and neck | Mutation burden | Positive | Yes | Improved responsiveness to immunotherapy | [174] |
Lung | 3B | Adverse | No | Shorter survival | [182] |
3B | Adverse | No | Shorter disease-free and overall survival with more with lymph node involvement and higher TNM stage | [183] | |
3B | Adverse | No | Shorter overall survival | [175] | |
Mutation burden | Adverse | No | Worse overall survival | [184] | |
Mutation burden | Adverse | No | Signature 2 (but not 13) burden associated with poor prognosis | [185] | |
3B | None | No | No association with pathological features or clinical outcomes | [54] | |
Mutation burden | Positive | Yes | Increased response to immune checkpoint blockade therapy | [166] | |
3B | Positive | Yes | Improved responsiveness to immune checkpoint blockade therapy | [36] | |
Nasopharyngeal | 3B | Adverse | No | Aggressive disease and poor outcomes | [55] |
Neuroendocrine tumor | 3B | Adverse | No | More lymph node metastasis | [40] |
Ovarian | Mutation burden | Positive | No | Improved progression-free and overall survival | [186] |
3B | Adverse | No | Shorter disease-free and overall survival | [42] | |
3B | Positive | No | Longer progression-free (significant) and overall (not significant) | [41] | |
3G | Positive | No | Favorable clinical outcomes with A3G, but no association for A3B | [167] | |
Pancreatic | 3G | None | No | No association with tumor stage, tumor type, or prognosis | [49] |
Renal | 3B | Adverse | No | More frequent recurrence | [169] |