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European Urology

European Urology

Volume 53, issue 2, pages 231-456, February 2008

Prostate Cancer

Marked Gene Transcript Level Alterations Occur Early During Radical Prostatectomy

Thorsten Schlomm, Esther Näkel, Andreas Lübke, Andreas Buness, Felix K.-H. Chun, Thomas Steuber, Markus Graefen, Ronald Simon, Guido Sauter, Annemarie Poustka, Hartwig Huland, Andreas Erbersdobler, Holger Sültmann and Olaf J.C. Hellwinkel

Accepted 28 March 2007, Published online 9 April 2007, pages 333 - 346


Abstract

Objectives

Gene expression analyses have become an important approach to understand the biology of cancer. However, transcript level patterns and RNA quality could rapidly change in response to ischemic and mechanical stress. Studies have shown that this occurs both perioperatively and after surgical removal of organs.

Methods

To better understand the relative importance of perioperative and postoperative gene expression changes, we performed quantitative reverse transcription-polymerase chain reactions on the transcripts of 91 cancer-related genes from normal and cancerous prostate tissues from 10 patients at eight different time points during surgical manipulation and after removal of the prostate.

Results

The mRNA levels of 8 (EGR1, p21, KRT17, PIM1, S100P, TNFRSF, WFDC2, and TRIM29) of 91 genes changed significantly with time of surgery in normal and tumor tissue. Remarkably, all eight genes were up-regulated, a reaction that was most prominent during the early intraoperative period. Additional changes occurred but were much less prominent during the first postoperative hour.

Conclusions

Our results substantially challenge the utility of immediate postoperative tissue sampling. At least for prostate cancer, the data suggest that preoperative tissue collection by core biopsies is optimal for studying molecular changes in normal and neoplastic prostate tissues.

Take Home Message

Major expression alterations of a significant subset of cancer-related genes occur early during surgery. This important bias needs to be considered for the planning and interpretation of gene expression studies in tissue samples.

Keywords: Degradation, Gene, Gene expression, Ischemia, Prostate cancer, RNA, Surgery.


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