Skip to main content

Characterizing the clinical relevance of an embryonic stem cell phenotype in lung adenocarcinoma.

Publication ,  Journal Article
Stevenson, MM; Mostertz, W; Acharya, C; Walters, K; Barry, W; Tuchman, S; Ready, N; Onaitis, M; Crawford, J; Potti, A
Published in: J Clin Oncol
May 20, 2009

11001 Background: Cancer cells possess traits reminiscent of those ascribed to normal stem cells. It is unclear whether these phenotypic similarities between normal/embryonic stem cells and mature tumor cells, specific to lung cancer, are a result of underlying biologic processes, such as specific molecular pathways and regulatory networks. METHODS: Using a large cohort of lung cancer cell lines with associated gene expression data, genes associated with an embryonic stem cell identity were used to develop a 'signature' representative of embryonic stemness (ES) activity specific to lung adenocarcinoma. Differential biology was evaluated using Gene Set Enrichment Analysis (GSEA) and signatures of oncogenic pathway deregulation. The ES signature was applied to three independent early (stage I - IIIa) lung adenocarcinoma data sets (N = 634) with clinically annotated gene expression data. The relationship between the ES phenotype and cisplatin sensitivity was also evaluated. RESULTS: Using Bayesian regression analysis, a 100 gene signature representative of ES activity in lung adenocarcinoma was developed and validated in a leave-one-out-analysis. GSEA identified gene sets significantly represented in the ES signature: signature of neoplastic transformation, signature of undifferentiated cancer, BRCA pathway, and fibroblast serum response pathway, all associated with cancer invasiveness. Adenocarcinomas with ES demonstrated increased activation of RAS (p = 0.0002), MYC (p = 0.0057), wound healing (angiogenesis) (p < 0.0001), chromosomal instability (p < 0.0001), and invasiveness (p < 0.0001) gene signatures. Adenocarcinomas (N= 634) with ES had a decreased survival (p<0.04). The ES signature was not prognostic in prostate, ovarian, or breast adenocarcinomas. Lung tumors (N=634) and adenocarcinoma cell lines (N=31) with ES were more resistant to cisplatin (p<0.0001 and p=0.0063, respectively). CONCLUSIONS: Lung adenocarcinomas that share a common gene expression pattern with normal stem cells were associated with decreased survival and increased likelihood of resistance to cisplatin, indicating the aggressiveness of lung tumors with a stem cell phenotype. No significant financial relationships to disclose.

Duke Scholars

Published In

J Clin Oncol

EISSN

1527-7755

Publication Date

May 20, 2009

Volume

27

Issue

15_suppl

Start / End Page

11001

Location

United States

Related Subject Headings

  • Oncology & Carcinogenesis
  • 1112 Oncology and Carcinogenesis
  • 1103 Clinical Sciences
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Stevenson, M. M., Mostertz, W., Acharya, C., Walters, K., Barry, W., Tuchman, S., … Potti, A. (2009). Characterizing the clinical relevance of an embryonic stem cell phenotype in lung adenocarcinoma. J Clin Oncol, 27(15_suppl), 11001.
Stevenson, M. M., W. Mostertz, C. Acharya, K. Walters, W. Barry, S. Tuchman, N. Ready, M. Onaitis, J. Crawford, and A. Potti. “Characterizing the clinical relevance of an embryonic stem cell phenotype in lung adenocarcinoma.J Clin Oncol 27, no. 15_suppl (May 20, 2009): 11001.
Stevenson MM, Mostertz W, Acharya C, Walters K, Barry W, Tuchman S, et al. Characterizing the clinical relevance of an embryonic stem cell phenotype in lung adenocarcinoma. J Clin Oncol. 2009 May 20;27(15_suppl):11001.
Stevenson, M. M., et al. “Characterizing the clinical relevance of an embryonic stem cell phenotype in lung adenocarcinoma.J Clin Oncol, vol. 27, no. 15_suppl, May 2009, p. 11001.
Stevenson MM, Mostertz W, Acharya C, Walters K, Barry W, Tuchman S, Ready N, Onaitis M, Crawford J, Potti A. Characterizing the clinical relevance of an embryonic stem cell phenotype in lung adenocarcinoma. J Clin Oncol. 2009 May 20;27(15_suppl):11001.

Published In

J Clin Oncol

EISSN

1527-7755

Publication Date

May 20, 2009

Volume

27

Issue

15_suppl

Start / End Page

11001

Location

United States

Related Subject Headings

  • Oncology & Carcinogenesis
  • 1112 Oncology and Carcinogenesis
  • 1103 Clinical Sciences