Clinically Relevant Characterization of Lung Adenocarcinoma Subtypes Based on Cellular Pathways: An International Validation Study

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 pathw...

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Vydáno v:PloS one Ročník 5; číslo 7; s. e11712
Hlavní autoři: Bryant, Christopher M., Albertus, Daniel L., Kim, Sinae, Chen, Guoan, Brambilla, Christian, Guedj, Mickael, Arima, Chinatsu, Travis, William D., Yatabe, Yasushi, Takahashi, Takashi, Brambilla, Elisabeth, Beer, David G.
Médium: Journal Article
Jazyk:angličtina
Vydáno: United States Public Library of Science 22.07.2010
Public Library of Science (PLoS)
Témata:
Adenocarcinoma
Adenocarcinoma - classification
Adenocarcinoma - metabolism
Adenocarcinoma - mortality
Adenocarcinoma - pathology
Advertising executives
Analysis
Cancer
Cell proliferation
Classification
Cluster Analysis
Clustering
Disease
Gene expression
Genes
Genetics and Genomics/Gene Expression
Genomes
Heterogeneity
Humans
Logistic Models
Lung cancer
Lung diseases
Lung Neoplasms - classification
Lung Neoplasms - metabolism
Lung Neoplasms - mortality
Lung Neoplasms - pathology
Medical prognosis
Medical schools
Molecular Biology/Bioinformatics
Morphogenesis
Mutation
Oncology/Lung Cancer
Pathology
Pathology/Surgical Pathology
Pathways
Signal Transduction - genetics
Signal Transduction - physiology
Stem cells
Studies
Subgroups
Surgery
Survival
Survival Analysis
Thoracic surgery
Tumors
New York
Ann Arbor Michigan
United States > US
Michigan
ISSN:1932-6203, 1932-6203
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Popis
Shrnutí: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.
Bibliografie:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
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Conceived and designed the experiments: CMB DLA DB. Analyzed the data: CMB DLA SK GC MG CA WT YY. Contributed reagents/materials/analysis tools: CB YY TT EB. Wrote the paper: CMB DLA DB.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0011712