Prognostic immune-related gene models for breast cancer: a pooled analysis

Figures & data

Figure 1 Flow chart for model selection process.

Table 1 Features of eight published models that prognosticate breast cancer outcomes

First author; publication year	Clinical subtype	Training data (n)	Validation data (n)	Gene signature
Teschendorff et al^Citation25 2007	ER−	713	343	7-gene panel: C1QA, IGIC2, LY9, TNFRSF17, SPP1, XCL2, HLA-F
Teschendorff et al^Citation26 2010	All	1,223	830	IL2, IL12, IFNG, IL4, IL13, TGFβ
Oh et al^Citation27 2012	LN−	684	616	UBE2C, PRC1, CCNB2, CDC20, CD3D, CD52, CCL19, TRBV20-1
Bianchini et al^Citation28 2010	ER+, HER2−, HER2+	684	233	15-gene panel: LYN, STK17A, CSF1R, PIM2, LCK, STK17B, BTK, HCK, PRKCB1, PRKCQ, FYN, ITK, ZAP70, MAP4K1, STK10
Nagalla et al^Citation29 2013	All	977	977	B/P metagenes, M/D metagenes, T/NK metagenes
Yau et al^Citation30 2010	ER−	199	75	14-gene panel: RG54, CXCL13, HAPLN1, HRBL, MATN1, PRTN3, SSX3, RPS28, EXOC7, ABO, CLIC5, RFXDC2, ZNF3, PRRG3
Ursini-Siegel et al^Citation31 2010	HER2+, basal	179	2,481	43-gene SRISa: CD247, CD3E, CD4, CD28, CTLA4, CXCL11, CXCL13, CXCL9, CXCR3, HLA-DQA1, IL1B, ITK, LAG3, LCK, NFATC2, PPIA, PTPRC, SLAMF6, SLAMF7, SLAMF9, TCRA, RELT, CD27, VTCN1, ATRN, CD69, ICOS, IL7R, B2M, CD8B, GZMB, IFNG, IL12B, LILRB3, TIA1, CD72, IGHG1, IGHM, IGHG2, IGJ, IL4, C1S, C3
Cheng et al^Citation32 2013	ER−	1,981	184	Lymphocyte-specific immune recruitment panel: PTPRC, CD53, LCP2, LAPTM5, DOCK2, IL10RA, CYBB, CD48, ITGB2, EVI2B

Notes:

a 43 gene ShcA-regulated immune signature (SRIS). See supplementary material for additional information.

Abbreviations: ER, estrogen receptor; HER2, human epidermal growth factor 2; LN, lymph node.

Table 2 Features of ten publicly available microarray data sets used to validate published risk scores

Data sets	Microarray platform	Sample size (n)	Information about ER	Information about LN
ETABM158	U133A	130	Yes	Yes
GSE11121	U133A	200	Yes	Yes
GSE2034	U133A	286	Yes	Yes
GSE25066	U133A	508	Yes	Yes
GSE2603	U133A	121	Yes	Yes
GSE3494-GPL96	U133A	251	Yes	Yes
GSE45255	U133A	139	Yes	Yes
GSE4922-GPL96	U133A	289	Yes	Yes
GSE6532-GPL96	U133A	327	Yes	Yes
GSE7390	U133A	198	Yes	Yes
Total		2,449	10	10

Abbreviations: ER, estrogen receptor; LN, lymph node.

Table 3 Heterogeneity analyses for eight publicly available models

First author; publication year	All data (P)	ER− (P)	ER+ (P)	LN+ (P)	LN− (P)
Nagalla et al^Citation29 2013	0.13	0.01	0.08	0.63	0.25
Teschendorff et al^Citation25 2007	0.01	0.05	0.07	0.91	0.14
Oh et al^Citation27 2012	0.12	0.02	0.07	0.68	0.01
Ursini-Siegel et al^Citation31 2010	0.18	0.13	0.30	0.47	0.01
Teschendorff et al^Citation26 2010	0.01	0.38	0.03	0.47	0.08
Bianchini et al^Citation28 2010	0.07	0.01	0.04	0.02	0.01
Cheng et al^Citation32 2013	0.01	0.08	0.33	0.67	0.97
Yau et al^Citation30 2010	0.15	0.29	0.31	0.99	0.16

Note: P-values of heterogeneity analyses in validation data sets are presented when analyzing all the data, ER−, ER+, LN+, and LN− cohorts, respectively.

Abbreviations: ER, estrogen receptor; LN, lymph node.

Figure 2 Performance assessment of published immune-related risk scores.

Notes: (A) C-indices are given for predictions of overall survival for each of eight models in each of ten microarray data sets (left panel). Data sets used as training data sets during model development are shown in black. Darker shades of orange corresponded to higher prediction levels; 0.5= random risk score, 1.0= perfect prediction. Models are ordered from the highest to the lowest summary C-index (top to bottom). Summary C-indices are given for each model with training data sets excluded (orange boxes; right panel); 95% CIs (gray lines) were obtained by resampling cases. C-indices are presented for predictions of overall survival in ER−, ER+, LN+, and LN− data sets (left panels of B–E, respectively). Summary C-indices in ER−, ER+, LN+, and LN− data sets are given for each model with training data sets excluded (orange boxes; right panels of B–E, respectively).
Abbreviations: C-indices, concordance indices; ER, estrogen receptor; LN, lymph node.

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