scholarly journals Alterations in Cell Cycle Genes in Early Stage Lung Adenocarcinoma Identified by Expression Profiling

2003 ◽  
Vol 2 (3) ◽  
pp. 291-298 ◽  
Author(s):  
Sunil Singhal ◽  
Kunjilata Amin ◽  
Robert Kruklitis ◽  
Peter DeLong ◽  
Michael E. Friscia ◽  
...  
2014 ◽  
Author(s):  
Yann Gaston-Mathé ◽  
CHARLES FERTE ◽  
benoit gauthier ◽  
mathilde bateson ◽  
david planchard ◽  
...  

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 7023-7023
Author(s):  
Carmen Behrens ◽  
Francesca Lombardi ◽  
Susanne Wagner ◽  
Junya Fujimoto ◽  
Maria G Raso ◽  
...  

7023 Background: Adjuvant treatment of patients with early-stage lung adenocarcinoma is based on post-surgical pathological staging and patient performance status. Disparate outcomes within each staging group suggest that additional prognostic markers could improve our understanding of risk-benefit and potentially lead to better treatment decisions. A proliferation-based, mRNA expression profile was applied to public microarray data of surgically treated lung adenocarcinomas and a cohort of FFPE samples to test its potential prognostic utility. Methods: Public expression data (Director’s Consortium, DC) were derived from Affymetrix HG-U133A arrays. Clinical FFPE samples were assayed by quantitative PCR. A cell cycle progression (CCP) score was calculated from the expression average of 31 cell cycle genes normalized by 15 housekeeper genes. The prognostic value of the CCP score to predict stage I and II patient outcomes was evaluated by Cox proportional hazards analysis with disease-related death as the primary outcome measure. Results: In 256 DC cases, the CCP score was a significant predictor of death in univariate (p=0.0001) and multivariate analysis (p=0.001, HR 1.57, 95%CI 1.20-2.05) using age, stage, gender, smoking status and treatment as covariates. Similarly, in a second data set (GSE31210, n=204) the CCP score was highly associated with death (univariate, p=0.001; multivariate analysis, p=0.003, HR 1.81, 95% CI 1.24-2.66). Using quantitative PCR, the signature was applied to 381 FFPE samples with a median follow-up of 5 years collected at the MD Anderson Cancer Center and the European Institute for Oncology. In the presence of clinical covariates (as above and tumor size and pleural invasion), the CCP score remained the most significant predictor of death in univariate (p=0.0003) and multivariate analysis (p=0.007, HR 1.50, 95% CI 1.11-2.02). Conclusions: A 46 gene mRNA signature is a significant predictor of disease-related death in early-stage lung adenocarcinoma, providing independent prognostic value in the presence of clinical variables. This molecular predictor of cancer survival will be studied in additional cohorts for its ability to impact clinical treatment decisions.


2013 ◽  
Vol 84 (1-2) ◽  
pp. 203-226 ◽  
Author(s):  
Hsiang-Yin Lin ◽  
Jhun-Chen Chen ◽  
Miao-Ju Wei ◽  
Yi-Chen Lien ◽  
Huang-Hsien Li ◽  
...  

Lung Cancer ◽  
2013 ◽  
Vol 80 (1) ◽  
pp. 91-98 ◽  
Author(s):  
Yafei Li ◽  
Hui Tang ◽  
Zhifu Sun ◽  
Aaron O. Bungum ◽  
Eric S. Edell ◽  
...  

2003 ◽  
Vol 2 (5) ◽  
pp. 566-571 ◽  
Author(s):  
Sunil Singhal ◽  
Kunjlata M. Amin ◽  
Robert Kruklitis ◽  
M. Blair Marshall ◽  
John C. Kucharczuk ◽  
...  

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 503-503
Author(s):  
M. Buess ◽  
M. Rajski ◽  
B. Vogel ◽  
R. Herrmann ◽  
C. Rochlitz

503 Background: The effects of tumor-endothelial interaction on global gene expression in breast cancer are not yet well characterized. We hypothesized that gene expression signatures induced by tumor-endothelial interaction might be of clinical relevance. Methods: To this aim we set up an ex vivo co-culture model with human benign and a panel of 6 malignant breast epithelial cells in combination with human venous and microvascular endothelial cells and determined associated gene expression changes with cDNA microarrays. Pretreatment gene expression profiles of 295 early stage breast cancers from the Netherlands Cancer Institute with a median follow up of 12.6 years allowed evaluating in vitro effects in vivo. Results: The most prominent response to co-culture was the induction of a set of “M-phase cell cycle” genes in a subset of breast cancer co-cultures, which were absent in co-cultures with normal breast epithelial cells. While in monoculture tumor cells containing the stem cell like CD44+/CD24- signature showed a lower expression of the “M-phase cell cycle” genes than the CD44-/CD24+ cells, in the co-cultures with CD44+/CD24- cells these genes were induced. Interestingly, these tumor cells co- expressed a set of angiogenic factors such as VEGF, PTN, and FGF12 mRNA at significantly higher levels. In vivo, the expression of the gene set derived from the co-culture was remarkably coherent providing a basis for segregation of tumors into two groups. In a univariate analysis, early stage tumors with high expression levels (n= 137) of “M-phase cell cycle” genes had a significantly lower distant metastasis-free survival (p=1.8e-5) (50 % at 10 years) and overall survival rate (p= 5e-9) (52 % at 10 years) than tumors with low expression levels (n= 158) (metastasis-free survival: 73 %; overall survival: 84 % at 10 years). Conclusions: Our results suggest that the interaction of tumor cells expressing the CD44+/CD24- stem cell like signature, implicating a low proliferative potential, with endothelial cells might explain the unexpected and paradoxical association of the CD44+/CD24- signature with highly proliferative tumors with an unfavorable prognosis. Multiple co-expressed angiogenic factors represent potentially interesting additional therapeutic targets. No significant financial relationships to disclose.


2013 ◽  
Vol 375 (1-2) ◽  
pp. 35-42 ◽  
Author(s):  
Jalal Taneera ◽  
Joao Fadista ◽  
Emma Ahlqvist ◽  
Mengze Zhang ◽  
Nils Wierup ◽  
...  

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