|
|||||
|
|
||||||
Originally published as JCO Early Release 10.1200/JCO.2005.05.1458 on July 5 2006 © 2006 American Society of Clinical Oncology. Influence of Surgical Manipulation on Prostate Gene Expression: Implications for Molecular Correlates of Treatment Effects and Disease Prognosis
From the Divisions of Human Biology and Public Health Sciences, Fred Hutchinson Cancer Research Center; and the Departments of Urology and Epidemiology, University of Washington, Seattle, WA Address reprint requests to Daniel W. Lin, MD, Department of Urology, Box 356510, 1959 NE Pacific St, University of Washington, Seattle, WA 98195; e-mail: dlin{at}u.washington.edu Purpose: Measurements of tissue gene expression are increasingly used for disease stratification, clinical trial eligibility, and assessment of neoadjuvant therapy response. However, the method of tissue acquisition alone could significantly influence the expression of specific transcripts or proteins. This study examines whether there are transcript alterations associated with surgical resection of the prostate gland by radical retropubic prostatectomy. Materials and Methods: Twelve patients with clinically localized prostate cancer underwent immediate in situ prostate biopsy after induction of anesthesia for radical prostatectomy. Ex vivo prostate biopsies were performed immediately after surgical removal. Prostate epithelium was acquired by laser-capture microdissection, and transcript abundance levels were quantitated by cDNA microarray hybridization and confirmed by quantitative polymerase chain reaction. Data were analyzed by paired, two-sample t test using Statistical Analysis of Microarray algorithms, and linear models were fit as a function of clinical characteristics.
Results: Of 5,753 cDNAs with measurable expression in prostate epithelium, 88 (1.5%) were altered as a result of surgery (false-discovery rate Conclusion: Surgical manipulation results in significant gene expression changes. Molecular analyses of surgical samples should recognize that transcript alterations occur rapidly, and these results are important when designing and analyzing molecular correlates of clinical studies. published online ahead of print at www.jco.org on July 5, 2006. Supported by Grant No. DK65083 (D.W.L.), the Pacific Northwest Prostate Cancer SPORE Grant No. CA97186 (D.W.L. and P.S.N.), and Grant No. CA85859 (P.S.N.). Terms in blue are defined in the glossary, found at the end of this article and online at www.jco.org. Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article. This article has been cited by other articles:
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||
|
Copyright © 2006 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
|