Marked gene transcript level alterations occur early during radical prostatectomy.
Author(s): Schlomm T, Näkel E, Lübke A, Buness A, Chun FK, Steuber T, Graefen M, Simon R, Sauter G, Poustka A, Huland H, Erbersdobler A, Sültmann H, Hellwinkel OJ
Publication: Eur Urol, 2008, Vol. 53, Page 333-44
PubMed ID: 17448597 PubMed Review Paper? No
Purpose of Paper
Conclusion of Paper
Studies
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Study Purpose
The purpose of this study was to assess potential alterations in gene expression induced by prostatectomy, associated warm ischemia time, as well as subsequent cold ischemia durations at room temperature.
Summary of Findings:
RNA quality, determined by 28S/18S ratio, was unaffected by the duration of surgery. Of the 91 genes analyzed by low density array (LDA) of pooled samples, 7 increased 2-fold or more within 80 min of blood flow restriction (warm ischemia time), with modest increases induced further by subsequent cold ischemia. Expression of targeted house-keeping genes (GAPDH, HPRT, TFRC) remained stable through out and after surgery. Real-time quantitative RT-PCR (qRT-PCR) analysis in individual samples supported LDA results, with significant increases in EGR1, KRT 17, PIM1, p21, WFDC2, S100P, TNFRSF, and TRIM29 expression after 45-70 min of warm ischemia. Comparisons among biopsies collected during and after surgery with those procured 1 d prior to surgery buttressed the observed changes in gene expression. Statistical analysis revealed that surgical duration (warm ischemia) alone was strongly associated with the observed differences in expression.
Biospecimens
Preservative Types
- Frozen
Diagnoses:
- Neoplastic - Carcinoma
- Neoplastic - Normal Adjacent
Platform:
Analyte Technology Platform RNA Real-time qRT-PCR RNA Automated electrophoresis/Bioanalyzer Pre-analytical Factors:
Classification Pre-analytical Factor Value(s) Preaquisition Patient age 50-68 y
Preaquisition Biomarker level 3-30 ng/ml PSA
Preaquisition Surgery duration 112-171 min
Preaquisition Warm ischemia time 0 min
45 min
70 min
80 min
Biospecimen Acquisition Cold ischemia time 10 min
20 min
30 min
60 min
Preaquisition Blood loss amount 300-1300 ml
Real-time qRT-PCR Specific Targeted nucleic acid GAPDH
HPRT
TFRC
EGR1
KRT17
PIM1
p21
WFDC2
S100P
TNFRSF
TRIM29
Biospecimen Acquisition Organ measurements 25-65 ml Prostate gland volume