Table 1. SVM gene expression signature performance on METABRIC patients.
Patient
treatment |
# of patients | Agent:
final gene signature (C and sigma) |
Accuracy (%) | Precision | F-Measure | MCC 1 | AUC 2 |
---|---|---|---|---|---|---|---|
Both CT
and HT 3 |
84 | Paclitaxel:
ABCC1, ABCC10, BAD,
BIRC5, FN1, GBP1, MAPT, SLCO1B3, TMEM243, TUBB3, TUBB4B (C=10000, σ=10) |
78.6 | 0.787 | 0.782 | 0.559 | 0.814 |
Tamoxifen:
ABCC2, ALB, CCNA2,
E2F7, FLAD1, FMO1, NCOA2, NR1I2, PIAS4, SULT1E1 (C=100000, σ=100) |
76.2 | 0.761 | 0.760 | 0.510 | 0.701 | ||
Methotrexate:
ABCC2, ABCG2,
CDK2, DHFRL1 (C=10, σ=1) |
71.4 | 0.712 | 0.711 | 0.410 | 0.766 | ||
Epirubicin
: ABCB1, CDA, CYP1B1,
ERBB3, ERCC1, MTHFR, PON1, SEMA4D, TFDP2 (C=1000, σ=10) |
72.6 | 0.725 | 0.723 | 0.434 | 0.686 | ||
Doxorubicin:
ABCC2, ABCD3, CBR1,
FTH1, GPX1, NCF4, RAC2, TXNRD1 (C=100000, σ=100) |
75.0 | 0.749 | 0.750 | 0.488 | 0.701 | ||
5-Fluorouracil:
ABCB1, ABCC3,
MTHFR, TP53 (C=10000, σ=100) |
71.4 | 0.714 | 0.714 | 0.417 | 0.718 | ||
CT and/or
HT 3, 4, 5, 6 |
735 | Paclitaxel:
BAD, BCAP29, BCL2,
BMF, CNGA3, CYP2C8, CYP3A4, FGF2, FN1, NFKB2, NR1I2, OPRK1, SLCO1B3, TLR6, TUBB1, TUBB3, TUBB4A, TUBB4B, TWIST1 (C=10000, σ=100) |
66.1 | 0.652 | 0.643 | 0.287 | 0.660 |
Deceased
only 2, 6, 7 (CT and/or HT) |
327 | Paclitaxel:
ABCB11, BAD, BBC3,
BCL2, BCL2L1, BIRC5, CYP2C8, FGF2, FN1, GBP1, MAPT, NFKB2, OPRK1, SLCO1B3, TMEM243 (C=100, σ=10) |
75.3 | 0.752 | 0.752 | 0.505 | 0.763 |
No
treatment 3 |
304 | Paclitaxel:
ABCB1, ABCB11, BBC3,
BCL2L1, BMF, CYP3A4, FGF2, GBP1, MAP4, MAPT, NR1I2, OPRK1, SLCO1B3, TUBB4A, TUBB4B, TWIST2 (C=100, σ=10) |
73.4 | 0.734 | 0.733 | 0.467 | 0.769 |
Initial gene sets preceding feature selection: Paclitaxel - ABCB1, ABCB11, ABCC1, ABCC10, BAD, BBC3, BCAP29, BCL2, BCL2L1, BIRC5, BMF, CNGA3, CYP2C8, CYP3A4, FGF2, FN1, GBP1, MAP2, MAP4, MAPT, NFKB2, NR1I2, OPRK1, SLCO1B3, TLR6, TUBB1, TWIST1. Tamoxifen - ABCB1, ABCC2, ALB, C10ORF11, CCNA2, CYP3A4, E2F7, F5, FLAD1, FMO1, IGF1, IGFBP3, IRS2, NCOA2, NR1H4, NR1I2, PIAS4, PPARA, PROC, RXRA, SMARCD3, SULT1B1, SULT1E1, SULT2A1. Methotrexate - ABCB1, ABCC2, ABCG2, CDK18, CDK2, CDK6, CDK8, CENPA, DHFRL1. Epirubicin - ABCB1, CDA, CYP1B1, ERBB3, ERCC1, GSTP1, MTHFR, NOS3, ODC1, PON1, RAD50, SEMA4D, TFDP2. Doxorubicin - ABCB1, ABCC2, ABCD3, AKR1B1, AKR1C1, CBR1, CYBA, FTH1, FTL, GPX1, MT2A, NCF4, RAC2, SLC22A16, TXNRD1. 5-Fluorouracil - ABCB1, ABCC3, CFLAR, IL6, MTHFR, TP53, UCK2. 1MCC: Matthews Correlation Coefficient. 2AUC: Area under receiver operating curve. 3 Surviving patients; 4 Analysis included patients in the METABRIC ‘discovery’ dataset only; 5 SVMs tested with 9 fold cross-validation, all others tested with leave-one-out cross-validation; 6 Includes all patients treated with HT,CT, combination CT/HT, either with or without combination radiotherapy; 7 Median time after treatment until death (> 4.4 years) was used to distinguish favorable outcome, ie. sensitivity to therapy.