NIH, National Cancer Institute, Division of Cancer Treatment and Diagnosis (DCTD) NIH - National Institutes of Health National Cancer Institute DCTD - Division of Cancer Treatment and Diagnosis

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

This paper assessed gene expression within prostate biopsies before, during, and after radical prostatectomy to determine the influence of surgical, warm ischemia, and cold ischemia durations.

Conclusion of Paper

Warm ischemia time (approximately 45-70 min) increased mRNA levels of 8% of the 91 genes analyzed in a gene-dependent manner. Of the genes affected, the majority displayed further, although modest, increases in expression after cold ischemia durations of 10-60 min.

Studies

  1. 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:
    AnalyteTechnology Platform
    RNA Real-time qRT-PCR
    RNA Automated electrophoresis/Bioanalyzer
    Pre-analytical Factors:
    ClassificationPre-analytical FactorValue(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

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