by Wei-Yi Cheng, Tai-Hsien Ou Yang, and Dimitris Anastassiou

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Date of download: 5/29/2016 Copyright © 2016 American Medical Association. All rights reserved. From: Gene Expression Signatures, Clinicopathological Features,

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Presentation transcript:

by Wei-Yi Cheng, Tai-Hsien Ou Yang, and Dimitris Anastassiou Development of a Prognostic Model for Breast Cancer Survival in an Open Challenge Environment by Wei-Yi Cheng, Tai-Hsien Ou Yang, and Dimitris Anastassiou Sci Transl Med Volume 5(181):181ra50-181ra50 April 17, 2013 Copyright © 2013, American Association for the Advancement of Science

Fig. 1 Mitotic CIN attractor metagene. Mitotic CIN attractor metagene.(A and B) Kaplan-Meier cumulative survival curves of breast cancer patients over a 15-year period on the basis of the mitotic CIN attractor metagene expression—represented by the CIN feature—in the (A) METABRIC and (B) OsloVal data sets. The patients were divided into equal-sized “high” and “low” CIN-expressing subgroups according to their ranking with respect to expression values of the CIN feature. High expression of the mitotic CIN attractor metagene was associated with poorer survival in both data sets. P values derived using the log-rank test in the two data sets were less than 2 × 10−16 and 0.041, respectively. Wei-Yi Cheng et al., Sci Transl Med 2013;5:181ra50 Copyright © 2013, American Association for the Advancement of Science

Fig. 2 LYM attractor metagene. LYM attractor metagene.(A and B) Kaplan-Meier cumulative survival curves of ER-negative breast cancer patients over a 15-year period on the basis of LYM attractor metagene expression—represented by the LYM feature—in the (A) METABRIC and (B) OsloVal data sets. The ER-negative breast cancer patients were divided into equal-sized high and low LYM-expressing subgroups according to their ranking with respect to expression values of the LYM feature. High expression of the LYM attractor metagene was associated with improved survival in both data sets. P values derived using the log-rank test in the two data sets were 0.0024 and 0.0223, respectively. (C) Kaplan-Meier cumulative survival curves of ER-positive breast cancer patients with more than four positive lymph nodes over a 15-year period on the basis of LYM attractor metagene expression—represented by the LYM feature—in the METABRIC data set. ER-positive breast cancer patients with more than four positive lymph nodes were divided into equal-sized high and low LYM-expressing subgroups according to their ranking with respect to expression values of the LYM feature. In contrast to (A), high expression of the LYM attractor metagene was associated with poorer survival in this patient subset. The P value derived using the log-rank test was 0.0278. There were only 19 corresponding samples in the OsloVal data set, insufficient for validation of this reversal relative to (B). Wei-Yi Cheng et al., Sci Transl Med 2013;5:181ra50 Copyright © 2013, American Association for the Advancement of Science

Fig. 3 FGD3-SUSD3 metagene. FGD3-SUSD3 metagene.(A) A scatter plot of the expression of SUSD3 versus FGD3 in the METABRIC data set shows a high variance in the expression of both genes at high expression levels. On the other hand, low expression of one strongly suggests low expression of the other in breast tumors. (B) ER-negative breast tumors tended not to express the FGD3-SUSD3 metagene, whereas ER-positive breast tumors may or may not express the FGD3-SUSD3 metagene. (C and D) Kaplan-Meier cumulative survival curves of breast cancer patients over a 15-year period on the basis of FGD3-SUSD3 metagene expression in the (C) METABRIC and (D) OsloVal data sets. Patients were divided into equal-sized high and low subgroups according to their ranking with respect to FGD3-SUSD3 metagene expression values. Low levels of FGD3-SUSD3 metagene expression were associated with poor survival in both data sets. P values derived using the log-rank test in the two data sets were less than 2 × 10−16 and 0.0028, respectively. Wei-Yi Cheng et al., Sci Transl Med 2013;5:181ra50 Copyright © 2013, American Association for the Advancement of Science

Fig. 4 Final ensemble model. Final ensemble model.Shown are Kaplan-Meier cumulative survival curves of breast cancer patients over a 15-year period on the basis of the predictions made by the final ensemble model in the OsloVal data set. The patients were divided into equal-sized poor and good predicted survival subgroups according to the ranking assigned by the final model, which was trained on the METABRIC data set. The P value derived using the log-rank test was less than 2 × 10−16. Wei-Yi Cheng et al., Sci Transl Med 2013;5:181ra50 Copyright © 2013, American Association for the Advancement of Science

Fig. 5 Schematic of model development. Schematic of model development.Shown are block diagrams that describe the development stages for our final ensemble prognostic model. Building a prognostic model involves derivation of relevant features, training submodels and making predictions, and combining predictions from each submodel. Our model derived the attractor metagenes using gene expression data, combined them with the clinical information through Cox regression, GBM, and KNN techniques, and eventually blended each submodel’s prediction. Wei-Yi Cheng et al., Sci Transl Med 2013;5:181ra50 Copyright © 2013, American Association for the Advancement of Science