Candidate genes with LR test P < .05 and treatment-mRNA interaction P < .05 in models with or without adjusting for known prognostic factors
| Gene symbol . | Gene name . | Median (5%-95%) . | HR (95% CI) of R-FC vs FC . | P (from expanded model) . | |||||
|---|---|---|---|---|---|---|---|---|---|
| Gene high (>median) . | Gene low (≤median) . | LR test . | Q value of LR test . | Tx-gene interaction . | Gene effect within FC . | Gene effect within R-FC . | |||
| HIST1H3I | Histone cluster 1, H3i | 9.1 (5.4-10.6) | 0.89 (0.59-1.34) | 0.47 (0.28-0.79) | 5e-04 (.00039) | .0098 (.15) | .013 (.029) | .5 (.33) | .00072 (.00043) |
| PTK2 | Protein tyrosine kinase 2 | 5.1 (3.9-7.1) | 0.48 (0.3-0.78) | 0.94 (0.62-1.45) | 5e-04 (.0027) | .0098 (.2) | .018 (.031) | .37 (.69) | .00041 (.00085) |
| HIST1H4K | Histone cluster 1, H4k | 9.3 (7.7-10.3) | 0.79 (0.52-1.19) | 0.55 (0.33-0.91) | .00083 (.00093) | .013 (.15) | .015 (.015) | .67 (.76) | .0017 (.00034) |
| IGF1R | Insulin-like growth factor 1 receptor | 4 (3.3-5.7) | 0.46 (0.3-0.71) | 0.95 (0.59-1.52) | .00096 (.0027) | .014 (.2) | .0017 (.00082) | 6.1e-05 (.0019) | .51 (.017) |
| NR3C2 | Nuclear receptor subfamily 3, group C, member 2 | 4.8 (4.1-6.7) | 0.53 (0.35-0.81) | 0.92 (0.57-1.49) | .0014 (.01) | .016 (.3) | .022 (.019) | .00012 (.00045) | .74 (.4) |
| HIP1R | Huntingtin-interacting protein 1 related | 6.9 (6.1-8.1) | 0.41 (0.25-0.67) | 1 (0.65-1.52) | .013 (.0028) | .052 (.2) | .0064 (.015) | .18 (.86) | .015 (.0012) |
| STAP1 | Signal transducing adaptor family member 1 | 5.2 (4.2-6.3) | 0.61 (0.38-0.96) | 0.73 (0.47-1.14) | .021 (.027) | .068 (.35) | .0059 (.0078) | .032 (.068) | .072 (.082) |
| Gene symbol . | Gene name . | Median (5%-95%) . | HR (95% CI) of R-FC vs FC . | P (from expanded model) . | |||||
|---|---|---|---|---|---|---|---|---|---|
| Gene high (>median) . | Gene low (≤median) . | LR test . | Q value of LR test . | Tx-gene interaction . | Gene effect within FC . | Gene effect within R-FC . | |||
| HIST1H3I | Histone cluster 1, H3i | 9.1 (5.4-10.6) | 0.89 (0.59-1.34) | 0.47 (0.28-0.79) | 5e-04 (.00039) | .0098 (.15) | .013 (.029) | .5 (.33) | .00072 (.00043) |
| PTK2 | Protein tyrosine kinase 2 | 5.1 (3.9-7.1) | 0.48 (0.3-0.78) | 0.94 (0.62-1.45) | 5e-04 (.0027) | .0098 (.2) | .018 (.031) | .37 (.69) | .00041 (.00085) |
| HIST1H4K | Histone cluster 1, H4k | 9.3 (7.7-10.3) | 0.79 (0.52-1.19) | 0.55 (0.33-0.91) | .00083 (.00093) | .013 (.15) | .015 (.015) | .67 (.76) | .0017 (.00034) |
| IGF1R | Insulin-like growth factor 1 receptor | 4 (3.3-5.7) | 0.46 (0.3-0.71) | 0.95 (0.59-1.52) | .00096 (.0027) | .014 (.2) | .0017 (.00082) | 6.1e-05 (.0019) | .51 (.017) |
| NR3C2 | Nuclear receptor subfamily 3, group C, member 2 | 4.8 (4.1-6.7) | 0.53 (0.35-0.81) | 0.92 (0.57-1.49) | .0014 (.01) | .016 (.3) | .022 (.019) | .00012 (.00045) | .74 (.4) |
| HIP1R | Huntingtin-interacting protein 1 related | 6.9 (6.1-8.1) | 0.41 (0.25-0.67) | 1 (0.65-1.52) | .013 (.0028) | .052 (.2) | .0064 (.015) | .18 (.86) | .015 (.0012) |
| STAP1 | Signal transducing adaptor family member 1 | 5.2 (4.2-6.3) | 0.61 (0.38-0.96) | 0.73 (0.47-1.14) | .021 (.027) | .068 (.35) | .0059 (.0078) | .032 (.068) | .072 (.082) |
P values in the parentheses were derived from respective expanded models that included additional known prognostic factors (age, Binet stage, ECOG status, β2-microglobulin, IGHV mutational status, and del[17p]) as covariates, as described in “Methods.” LR test refers to the LR test with 2 degrees of freedom to test for the model with treatment (Tx) + gene + TX-gene interaction vs the treatment-only model, as a way to assess the utility of each mRNA to predict PFS. Gene effect within FC measures the prognostic effect of the gene by computing HRs and associated statistical significance in FC patients with high (≥median) vs low (<median) level of gene expression.