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Adverse Drug Events-based Tumor Stratification for Ovarian Cancer Patients Receiving Platinum Therapy.

Wang C, Zimmermann MT, Chute CG, Jiang G - AMIA Jt Summits Transl Sci Proc (2015)

Bottom Line: The underlying molecular mechanisms of adverse drug events (ADEs) associated with cancer therapy drugs may overlap with their antineoplastic mechanisms.We identified a cohort of ovarian cancer patients receiving cisplatin (a standard platinum therapy) from The Cancer Genome Atlas (TCGA) (n=156).We demonstrated that somatic variant prioritization guided by known ADEs associated with cisplatin could be used to stratify patients treated with cisplatin and uncover tumor subtypes with different clinical outcomes.

View Article: PubMed Central - PubMed

Affiliation: Department of Health Sciences Research, Mayo Clinic, Rochester, MN.

ABSTRACT
The underlying molecular mechanisms of adverse drug events (ADEs) associated with cancer therapy drugs may overlap with their antineoplastic mechanisms. In a previous study, we developed an ADE-based tumor stratification framework (known as ADEStrata) with a case study of breast cancer patients receiving aromatase inhibitors, and demonstrated that the prediction of per-patient ADE propensity simultaneously identifies high-risk patients experiencing poor outcomes. In this study, we aim to evaluate the ADEStrata framework with a different tumor type and chemotherapy class - ovarian cancer treated with platinum chemotherapeutic drugs. We identified a cohort of ovarian cancer patients receiving cisplatin (a standard platinum therapy) from The Cancer Genome Atlas (TCGA) (n=156). We demonstrated that somatic variant prioritization guided by known ADEs associated with cisplatin could be used to stratify patients treated with cisplatin and uncover tumor subtypes with different clinical outcomes.

No MeSH data available.


Related in: MedlinePlus

An ordered heatmap showing pathway-level clustering of 92 patients treated with cisplatin across ADE relevant variants. The color of heatmap from white to red indicates low to high percentages (0% to 100%) of genes affected by ADE relevant variants. Column color-bar on top of the heatmap indicates two clusters of samples: Cluster 1 (green) and Cluster 2 (black). Note that the number of the patients (n=92) with pathway enrichment is less than total number of the identified cohort (n=156) is because not all patients have prioritized variants listed.
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f1-2092016: An ordered heatmap showing pathway-level clustering of 92 patients treated with cisplatin across ADE relevant variants. The color of heatmap from white to red indicates low to high percentages (0% to 100%) of genes affected by ADE relevant variants. Column color-bar on top of the heatmap indicates two clusters of samples: Cluster 1 (green) and Cluster 2 (black). Note that the number of the patients (n=92) with pathway enrichment is less than total number of the identified cohort (n=156) is because not all patients have prioritized variants listed.

Mentions: By hierarchical clustering, 2 distinct patient clusters, organized by pathways (affected by prioritized variants), were identified and are displayed in Figure 1 containing 16 and 76 patients each. Table 2 shows the results of the univariate and multivariate cox-regression analysis for the three clusters. We found that Cluster 2 has a relatively large number of patients (n=76), and is significantly association with poorer survival time in both univariate and multivariate analysis. Table 3 shows the distribution of age and stage in the 2 clusters identified. There is no significant association between the 3 clusters and age/stage, although we noticed that Cluster 2 is enriched with more Stage IIIC and Grade 3 patient cases. Figure 2 shows a Kaplan-Meier plot of survival time for the 2 clusters, derived from our pathway-level analysis, indicating Cluster 2 had the worse survival outcome associated.


Adverse Drug Events-based Tumor Stratification for Ovarian Cancer Patients Receiving Platinum Therapy.

Wang C, Zimmermann MT, Chute CG, Jiang G - AMIA Jt Summits Transl Sci Proc (2015)

An ordered heatmap showing pathway-level clustering of 92 patients treated with cisplatin across ADE relevant variants. The color of heatmap from white to red indicates low to high percentages (0% to 100%) of genes affected by ADE relevant variants. Column color-bar on top of the heatmap indicates two clusters of samples: Cluster 1 (green) and Cluster 2 (black). Note that the number of the patients (n=92) with pathway enrichment is less than total number of the identified cohort (n=156) is because not all patients have prioritized variants listed.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4525249&req=5

f1-2092016: An ordered heatmap showing pathway-level clustering of 92 patients treated with cisplatin across ADE relevant variants. The color of heatmap from white to red indicates low to high percentages (0% to 100%) of genes affected by ADE relevant variants. Column color-bar on top of the heatmap indicates two clusters of samples: Cluster 1 (green) and Cluster 2 (black). Note that the number of the patients (n=92) with pathway enrichment is less than total number of the identified cohort (n=156) is because not all patients have prioritized variants listed.
Mentions: By hierarchical clustering, 2 distinct patient clusters, organized by pathways (affected by prioritized variants), were identified and are displayed in Figure 1 containing 16 and 76 patients each. Table 2 shows the results of the univariate and multivariate cox-regression analysis for the three clusters. We found that Cluster 2 has a relatively large number of patients (n=76), and is significantly association with poorer survival time in both univariate and multivariate analysis. Table 3 shows the distribution of age and stage in the 2 clusters identified. There is no significant association between the 3 clusters and age/stage, although we noticed that Cluster 2 is enriched with more Stage IIIC and Grade 3 patient cases. Figure 2 shows a Kaplan-Meier plot of survival time for the 2 clusters, derived from our pathway-level analysis, indicating Cluster 2 had the worse survival outcome associated.

Bottom Line: The underlying molecular mechanisms of adverse drug events (ADEs) associated with cancer therapy drugs may overlap with their antineoplastic mechanisms.We identified a cohort of ovarian cancer patients receiving cisplatin (a standard platinum therapy) from The Cancer Genome Atlas (TCGA) (n=156).We demonstrated that somatic variant prioritization guided by known ADEs associated with cisplatin could be used to stratify patients treated with cisplatin and uncover tumor subtypes with different clinical outcomes.

View Article: PubMed Central - PubMed

Affiliation: Department of Health Sciences Research, Mayo Clinic, Rochester, MN.

ABSTRACT
The underlying molecular mechanisms of adverse drug events (ADEs) associated with cancer therapy drugs may overlap with their antineoplastic mechanisms. In a previous study, we developed an ADE-based tumor stratification framework (known as ADEStrata) with a case study of breast cancer patients receiving aromatase inhibitors, and demonstrated that the prediction of per-patient ADE propensity simultaneously identifies high-risk patients experiencing poor outcomes. In this study, we aim to evaluate the ADEStrata framework with a different tumor type and chemotherapy class - ovarian cancer treated with platinum chemotherapeutic drugs. We identified a cohort of ovarian cancer patients receiving cisplatin (a standard platinum therapy) from The Cancer Genome Atlas (TCGA) (n=156). We demonstrated that somatic variant prioritization guided by known ADEs associated with cisplatin could be used to stratify patients treated with cisplatin and uncover tumor subtypes with different clinical outcomes.

No MeSH data available.


Related in: MedlinePlus