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Clinically relevant characterization of lung adenocarcinoma subtypes based on cellular pathways: an international validation study.

Bryant CM, Albertus DL, Kim S, Chen G, Brambilla C, Guedj M, Arima C, Travis WD, Yatabe Y, Takahashi T, Brambilla E, Beer DG - PLoS ONE (2010)

Bottom Line: Further, AD with increased cell proliferation demonstrate significantly poorer outcome and an increased solid AD subtype component.Additional results suggest the ability to use a similar approach to determine a patient's sensitivity to targeted treatment.We then demonstrated the consistency of these findings using two independent AD cohorts from Asia (N = 87) and Europe (N = 89) using the identical analytic procedures.

View Article: PubMed Central - PubMed

Affiliation: Thoracic Surgery, Department of Surgery, University of Michigan Medical School, Ann Arbor, Michigan, United States of America.

ABSTRACT
Lung adenocarcinoma (AD) represents a predominant type of lung cancer demonstrating significant morphologic and molecular heterogeneity. We sought to understand this heterogeneity by utilizing gene expression analyses of 432 AD samples and examining associations between 27 known cancer-related pathways and the AD subtype, clinical characteristics and patient survival. Unsupervised clustering of AD and gene expression enrichment analysis reveals that cell proliferation is the most important pathway separating tumors into subgroups. Further, AD with increased cell proliferation demonstrate significantly poorer outcome and an increased solid AD subtype component. Additionally, we find that tumors with any solid component have decreased survival as compared to tumors without a solid component. These results lead to the potential to use a relatively simple pathological examination of a tumor in order to determine its aggressiveness and the patient's prognosis. Additional results suggest the ability to use a similar approach to determine a patient's sensitivity to targeted treatment. We then demonstrated the consistency of these findings using two independent AD cohorts from Asia (N = 87) and Europe (N = 89) using the identical analytic procedures.

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Clusters show survival differences.Kaplan-Meier survival curves for 432 lung adenocarcinomas (AD) showing a significant difference between clusters (log-rank test: p = 0.000194). Abbreviations: Cluster 1, left most cluster in Figure 2; Cluster 2, middle cluster is Figure 2; Cluster 3, right most cluster in Figure 2.
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pone-0011712-g003: Clusters show survival differences.Kaplan-Meier survival curves for 432 lung adenocarcinomas (AD) showing a significant difference between clusters (log-rank test: p = 0.000194). Abbreviations: Cluster 1, left most cluster in Figure 2; Cluster 2, middle cluster is Figure 2; Cluster 3, right most cluster in Figure 2.

Mentions: Hierarchical clustering of all 432 samples with the 16,660 most variably expressed genes yielded three distinct lung AD groups. A dendrogram of the three clusters including a heat-map of the 200 most significantly over-expressed genes in each cluster is shown in Figure 2. The patients within each cluster demonstrated a significant (p-value <0.001) difference in overall survival (Figure 3). Cluster 3 includes patients with worse overall survival and more poorly-differentiated whereas those in cluster 1 were more well-differentiated and had a more favorable outcome. Complete clinical and pathological descriptive statistics for each cluster are provided in Table 1.


Clinically relevant characterization of lung adenocarcinoma subtypes based on cellular pathways: an international validation study.

Bryant CM, Albertus DL, Kim S, Chen G, Brambilla C, Guedj M, Arima C, Travis WD, Yatabe Y, Takahashi T, Brambilla E, Beer DG - PLoS ONE (2010)

Clusters show survival differences.Kaplan-Meier survival curves for 432 lung adenocarcinomas (AD) showing a significant difference between clusters (log-rank test: p = 0.000194). Abbreviations: Cluster 1, left most cluster in Figure 2; Cluster 2, middle cluster is Figure 2; Cluster 3, right most cluster in Figure 2.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2908611&req=5

pone-0011712-g003: Clusters show survival differences.Kaplan-Meier survival curves for 432 lung adenocarcinomas (AD) showing a significant difference between clusters (log-rank test: p = 0.000194). Abbreviations: Cluster 1, left most cluster in Figure 2; Cluster 2, middle cluster is Figure 2; Cluster 3, right most cluster in Figure 2.
Mentions: Hierarchical clustering of all 432 samples with the 16,660 most variably expressed genes yielded three distinct lung AD groups. A dendrogram of the three clusters including a heat-map of the 200 most significantly over-expressed genes in each cluster is shown in Figure 2. The patients within each cluster demonstrated a significant (p-value <0.001) difference in overall survival (Figure 3). Cluster 3 includes patients with worse overall survival and more poorly-differentiated whereas those in cluster 1 were more well-differentiated and had a more favorable outcome. Complete clinical and pathological descriptive statistics for each cluster are provided in Table 1.

Bottom Line: Further, AD with increased cell proliferation demonstrate significantly poorer outcome and an increased solid AD subtype component.Additional results suggest the ability to use a similar approach to determine a patient's sensitivity to targeted treatment.We then demonstrated the consistency of these findings using two independent AD cohorts from Asia (N = 87) and Europe (N = 89) using the identical analytic procedures.

View Article: PubMed Central - PubMed

Affiliation: Thoracic Surgery, Department of Surgery, University of Michigan Medical School, Ann Arbor, Michigan, United States of America.

ABSTRACT
Lung adenocarcinoma (AD) represents a predominant type of lung cancer demonstrating significant morphologic and molecular heterogeneity. We sought to understand this heterogeneity by utilizing gene expression analyses of 432 AD samples and examining associations between 27 known cancer-related pathways and the AD subtype, clinical characteristics and patient survival. Unsupervised clustering of AD and gene expression enrichment analysis reveals that cell proliferation is the most important pathway separating tumors into subgroups. Further, AD with increased cell proliferation demonstrate significantly poorer outcome and an increased solid AD subtype component. Additionally, we find that tumors with any solid component have decreased survival as compared to tumors without a solid component. These results lead to the potential to use a relatively simple pathological examination of a tumor in order to determine its aggressiveness and the patient's prognosis. Additional results suggest the ability to use a similar approach to determine a patient's sensitivity to targeted treatment. We then demonstrated the consistency of these findings using two independent AD cohorts from Asia (N = 87) and Europe (N = 89) using the identical analytic procedures.

Show MeSH
Related in: MedlinePlus