Table 3. Prognostic significance of the common hypoxia metagene versus other hypoxia signatures.
Data (Table 1) | End point and significant clinical covariates (Cov.)a | In vitro hypoxia signature (Chi et al, 2006) | HN hypoxia metagene (Winter et al, 2007) | Initial seedsb | PCA scorec | CHM 51genes | Reduced CHMd k genes |
---|---|---|---|---|---|---|---|
NKI | End point: MFS Cov.: Age, tumour size, nodal status, grade, adj. treatment | 2.94 (1.39, 6.23) P=0.005 | 3.58 (1.53, 8.39) P=0.003 | 2.41 (1.05, 5.53) P=0.038 | 3.22 (1.37, 7.56) P=0.007 | 4.15 (1.73, 9.96) P=0.002 | 5.58 (2.41, 12.90) P<0.001, k=3 |
GSE2034e | End point: RFS Cov.: NA | 2.20 (1.11, 4.34) P=0.024 | 1.92 (0.97, 3.78) P=0.061 | 2.36 (0.95, 3.77) P=0.014 | 1.98 (1.01, 3.90) P=0.048 | 3.22 (1.63, 6.35) P=0.001 | 4.15 (2.10, 8.18) P<0.001, k=10 |
GSE3494e | End point: DSS Cov.: ER, PgR, tumour size, nodal status | 1.19 (0.45, 3.13) P=0.732 | 2.07 (0.77, 5.53) P=0.149 | 2.87 (1.25, 4.49) P=0.029 | 3.61 (1.33, 9.82) P=0.012 | 3.16 (1.05, 9.53) P=0.042 | 4.27 (1.53, 11.94) P=0.006, k=2 |
Chung | End point: RFS Cov.: Intrinsic sign., differentiation, batch (strata) | 3.06 (0.53, 17.6) P=0.210 | 14.83 (1.8, 122.4) P=0.012 | 6.71 (0.93, 48.4) P=0.059 | 1.25 (0.14, 11.4) P=0.840 | 6.25 (0.83, 47.2) P=0.077 | 34.66 (4.26, 281.95) P=0.001, k=2 |
Beer | End point: OS Cov.: Stage | 2.59 (1.59, 4.2) P=0.829 | 6.90 (1.34, 35.6) P=0.021 | 3.98 (0.72, 22.0) P=0.114 | 3.45 (0.59, 20.0) P=0.168 | 12.84 (1.71, 96.5) P=0.014 | 24.57 (2.83, 213.36) P=0.004, k=23 |
GSE4573 | End point: OS Cov.: Nodal status | 3.15 (1.32, 7.54) P=0.010 | 1.49 (0.65, 3.43) P=0.350 | 2.31 (0.93, 5.72) P=0.070 | 1.61 (1.14, 2.3) P=0.035 | 2.75 (1.15, 6.56) P=0.023 | 2.90 (1.27, 6.61) P=0.012, k=38 |
Abbreviations: CHM=common hypoxia metagene; DSS=disease-specific survival; ER/PgR=estrogen/progesterone receptor; MFS=metastases-free survival; RFS=recurrence-free survival; OS=overall survival.
Reduced models of clinical covariates are derived using backward-stepwise likelihood. Signature scores are entered into the reduced model; hazard ratio, 95% confidence limits and significance (model with and without the signature) are shown.
Summary score, E, is calculated for the signature including only the initial seeds.
Score obtained using principal components analysis (Supplementary Methods).
At convergence in the cumulative forest plots.
These two data sets were used to develop the signature but no training on outcome was carried out.