JCO Early Release, published online ahead of print Mar 20 2006
Journal of Clinical Oncology, 10.1200/JCO.2005.03.8224
Received August 12, 2005
Accepted October 27, 2005
Expression Profile-Defined Classification of Lung Adenocarcinoma Shows Close Relationship With Underlying Major Genetic Changes and Clinicopathologic Behaviors
Toshiyuki Takeuchi , Shuta Tomida , Yasushi Yatabe , Takayuki Kosaka , Hirotaka Osada , Kiyoshi Yanagisawa , Tetsuya Mitsudomi , and Takashi Takahashi *
From the Division of Molecular Carcinogenesis, Center for Neurological Diseases and Cancer, Nagoya University Graduate School of Medicine; Department of Pathology and Molecular Diagnostics, Aichi Cancer Center Hospital; Department of Thoracic Surgery, Aichi Cancer Center Hospital; Division of Molecular Oncology, Aichi Cancer Center Research Institute, Nagoya, Japan; and the Japan Biological Informatics Consortium, Tokyo, Japan.
* To whom correspondence should be addressed. E-mail: tak{at}med.nagoya-u.ac.jp
Purpose: This study was conducted to gain insight into the relationship between expression profiles and underlying genetic changes, which are known to be important for the pathogenesis of lung cancers.
Methods: Expression profiles of 18,175 unique genes and three major targets for genetic changes, p53, epidermal growth factor receptor (EGFR), and K-ras, were investigated in 149 patients with non-small-cell lung cancer, including 90 patients with adenocarcinoma to determine their relationships with various clinicopathologic features and Gene Ontology (GO) terms.
Results: This study successfully established a basis for expression profile-defined classification, which can classify adenocarcinomas into two major types, terminal respiratory unit (TRU) type and non-TRU type. Our GO term-based identifier of particular biologic processes, molecular functions, and cellular compartments clearly showed characteristic retention of normal peripheral lung features in TRU type, in sharp contrast to the significant association of non-TRU type with cell cycling and proliferation-related features. While significantly higher frequency of EGFR mutation was observed in TRU type, we found that the presence of EGFR mutations was a significant predictor of shorter postoperative survival for TRU type, independent of disease stage. We were also able to identify a set of genes in vivo with significant upregulation in the presence of EGFR mutations.
Conclusion: This study has shed light on heterogeneity in lung cancers, especially in adenocarcinomas, by establishing a molecularly, genetically, and clinically relevant, expression profile-defined classification. Future studies using independent patient cohorts are warranted to confirm the prognostic significance of EGFR mutations in TRU-type adenocarcinoma.
 CiteULike  Complore  Connotea  Del.icio.us  Digg  Facebook  Reddit  Technorati  Twitter What's this?
This article has been cited by other articles:
|
|
|
|
 
S. Tomida, T. Takeuchi, Y. Shimada, C. Arima, K. Matsuo, T. Mitsudomi, Y. Yatabe, and T. Takahashi
Relapse-Related Molecular Signature in Lung Adenocarcinomas Identifies Patients With Dismal Prognosis
J. Clin. Oncol.,
June 10, 2009;
27(17):
2793 - 2799.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. Brambilla and A. Gazdar
Pathogenesis of lung cancer signalling pathways: roadmap for therapies
Eur. Respir. J.,
June 1, 2009;
33(6):
1485 - 1497.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Dubey and C. A. Powell
Update in Lung Cancer 2008
Am. J. Respir. Crit. Care Med.,
May 15, 2009;
179(10):
860 - 868.
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Ebi, S. Tomida, T. Takeuchi, C. Arima, T. Sato, T. Mitsudomi, Y. Yatabe, H. Osada, and T. Takahashi
Relationship of Deregulated Signaling Converging onto mTOR with Prognosis and Classification of Lung Adenocarcinoma Shown by Two Independent In silico Analyses
Cancer Res.,
May 1, 2009;
69(9):
4027 - 4035.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. C. Borczuk, R. L. Toonkel, and C. A. Powell
Genomics of Lung Cancer
Proceedings of the ATS,
April 15, 2009;
6(2):
152 - 158.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Z. Hammoud, B. Tan, S. Badve, and R. M Bigsby
Estrogen promotes tumor progression in a genetically defined mouse model of lung adenocarcinoma
Endocr. Relat. Cancer,
June 1, 2008;
15(2):
475 - 483.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Yatabe, T. Takahashi, and T. Mitsudomi
Epidermal Growth Factor Receptor Gene Amplification Is Acquired in Association with Tumor Progression of EGFR-Mutated Lung Cancer
Cancer Res.,
April 1, 2008;
68(7):
2106 - 2111.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Osada, S. Tomida, Y. Yatabe, Y. Tatematsu, T. Takeuchi, H. Murakami, Y. Kondo, Y. Sekido, and T. Takahashi
Roles of Achaete-Scute Homologue 1 in DKK1 and E-cadherin Repression and Neuroendocrine Differentiation in Lung Cancer
Cancer Res.,
March 15, 2008;
68(6):
1647 - 1655.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Tanaka, K. Yanagisawa, K. Shinjo, A. Taguchi, K. Maeno, S. Tomida, Y. Shimada, H. Osada, T. Kosaka, H. Matsubara, et al.
Lineage-Specific Dependency of Lung Adenocarcinomas on the Lung Development Regulator TTF-1
Cancer Res.,
July 1, 2007;
67(13):
6007 - 6011.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. C. Borczuk and C. A. Powell
Expression Profiling and Lung Cancer Development
Proceedings of the ATS,
January 1, 2007;
4(1):
127 - 132.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. N. Hayes, S. Monti, G. Parmigiani, C. B. Gilks, K. Naoki, A. Bhattacharjee, M. A. Socinski, C. Perou, and M. Meyerson
Gene Expression Profiling Reveals Reproducible Human Lung Adenocarcinoma Subtypes in Multiple Independent Patient Cohorts
J. Clin. Oncol.,
November 1, 2006;
24(31):
5079 - 5090.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Albini and U. Pfeffer
A new tumor suppressor gene: invasion, metastasis, and angiogenesis as potential key targets.
J Natl Cancer Inst,
June 21, 2006;
98(12):
800 - 801.
[Full Text]
[PDF]
|
|
|
|
