Table 3.
Multivariate analysis of associationa between all factors and APOBEC3 members (APOBEC3A/B/C/D/F/G/H) mRNA overexpression (model A) or mutation (model B).
| A. APOBEC3 Overexpression modelb R2 = 14.0% |
B. APOBEC3 Mutation modelb R2 = 20.1% |
|||||
|---|---|---|---|---|---|---|
| Subgroups and factors | p value | OR | CI 95% | p value | OR | CI 95% |
| MICROSATELLITE STATUS | ||||||
| MSI-highc | ns | — | — | <0.0001 | 5.4 | [3–9.4] |
| POLYMERASES δ and ε | ||||||
| POLE mutated | ns | — | — | <0.0001 | 6.4 | [4.2–9.8] |
| MUTATION BURDEN | ||||||
| Number of mutations | ns | — | — | <0.0001 | 6.7 | [3.9–11.4] |
| Kataegis estimate | 0.0048 | 1.2 | [1.1–1.5] | ns | — | — |
| PD-1 LIGAND | ||||||
| Any PD-1 ligand mutated | ns | — | — | 0.0246 | 3.0 | [1.2–7.7] |
| Any PD-1 ligand overexpressed | <0.0001 | 2.6 | [2–3.2] | 0.0067 | 2.0 | [1.2–3.4] |
| AID/APOBEC FAMILY | ||||||
| APOBEC1 mutated | ns | — | — | 0.0009 | 4.0 | [1.8–9.1] |
| APOBEC2 mutated | ns | — | — | 0.0057 | 4.7 | [1.6–14.1] |
| APOBEC1 amplified | 0.0461 | 1.2 | [1–1.3] | ns | — | — |
| Any APOBEC3 amplified | <0.0001 | 2.3 | [1.9–2.7] | ns | — | — |
| AICDA overexpressed | <0.0001 | 2.2 | [1.5–3.3] | ns | — | — |
| LYMPHOCYTE MARKERS | ||||||
| CD3G overexpressed | <0.0001 | 2.0 | [1.5–2.8] | ns | — | — |
| CD4+ overexpressed | 0.0131 | 1.5 | [1.1–2] | ns | — | — |
| CD8A overexpressed | <0.0001 | 3.5 | [2.6–4.8] | ns | — | — |
| MS4A1 overexpressed | 0.0040 | 1.8 | [1.2–2.8] | ns | — | — |
| IL3RA overexpressed | 0.0025 | 1.6 | [1.2–2.1] | ns | — | — |
| CD33 overexpressed | <0.0001 | 2.1 | [1.5–2.9] | ns | — | — |
| IFNγ overexpressed | <0.0001 | 3.7 | [2.7–5] | ns | — | — |
Alterations with a p value ≤0.25 in univariate analysis were selected for multivariate analysis, respecting each model (i.e., using only single factors or single and relevant combined factors). A Fifth-corrected logistic regression with backward elimination was performed until all factors influencing the model present a p value ≤ 0.05. Only factors with p value ≤0.05 for a positive association in multivariate analysis using combined models are shown.
Combined factors as outlined in Table S2. For instance, any MMR member altered, any APOBEC3 member overexpressed, any PD-1 ligand mutated and total number of CNV represent combined factors.
MSI-status was dichotomized as MSI-high versus MSI-not high (MSS or MSI-low) and unknown versus MSI-not high (MSS or MSI-low).
Abbreviations: AID = Activation-induced deaminase; APOBEC= apolipoprotein B editing complex; CI 95% = 95% confidence interval; CNV = copy number variation; MMR = mismatch repair; MSI = microsatellite instability; MSI-High = microsatellite instability high; MSI-Low = microsatellite instability low; MSS = microsatellite stable; ns = non-significant; OR = Odds Ratio.