Clinically relevant characterization of lung adenocarcinoma subtypes based on cellular pathways: An international validation study Journal Article
| Authors: | Bryant, C. M.; Albertus, D. L.; Kim, S.; Chen, G.; Brambilla, C.; Guedj, M.; Arima, C.; Travis, W. D.; Yatabe, Y.; Takahashi, T.; Brambilla, E.; Beer, D. G. |
| Article Title: | Clinically relevant characterization of lung adenocarcinoma subtypes based on cellular pathways: An international validation study |
| 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. © 2010 Bryant et al. |
| Keywords: | signal transduction; survival; platelet derived growth factor; somatomedin; adult; cancer survival; controlled study; human tissue; aged; survival analysis; survival rate; gene cluster; overall survival; genetics; clinical feature; mortality; cancer growth; solid tumor; cancer staging; adenocarcinoma; cell proliferation; metabolism; vasculotropin receptor; cluster analysis; classification; embryonic stem cell; logistic models; lung neoplasms; sonic hedgehog protein; genetic association; notch receptor; pathology; validation study; physiology; cancer invasion; europe; lung tumor; gene expression regulation; cytokine; lung adenocarcinoma; asia; statistical model; lymphocyte count; genetic heterogeneity; complement; cancer growth factor |
| Journal Title: | PLoS ONE |
| Volume: | 5 |
| Issue: | 7 |
| ISSN: | 1932-6203 |
| Publisher: | Public Library of Science |
| Date Published: | 2010-07-22 |
| Start Page: | e11712 |
| Language: | English |
| DOI: | 10.1371/journal.pone.0011712 |
| PUBMED: | 20661423 |
| PROVIDER: | scopus |
| PMCID: | PMC2908611 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 2" - "Export Date: 20 April 2011" - "Art. No.: e11712" - "Source: Scopus" |
