Influence of hypoxia induced by minimally invasive prostatectomy on gene expression: Implications for biomarker analysis Journal Article

   


Authors: Erickson, H. S.; Josephson, J. W.; Vira, M.; Albert, P. S.; Gillespie, J. W.; Rodriguez-Canales, J.; Pinto, P. A.; Chuaqui, R. F.; Emmert-Buck, M. R.; Coleman, J. A.
Article Title: Influence of hypoxia induced by minimally invasive prostatectomy on gene expression: Implications for biomarker analysis
Abstract: Handling and processing of clinical specimens during and after surgical resection may significantly skew the molecular data obtained from analysis of those samples. Minimally invasive prostatectomy was used as a model to specifically study effects of surgical ischemia on gene expression in human clinical samples. Normal prostatic urethra cup biopsies were procured from 12 patients at three time points during laparoscopic radical prostatectomy. Homogeneous cells (stroma and epithelium) were microdissected. Transcript analysis of 3 oxygen-dependent, 3 oxygen-independent, and 3 control class genes was performed using quantitative RT-PCR. Data were analyzed by relative quantitation and two-sided t-test. Patient demographic and time covariates were fit by a linear mixed model. VEGF, an oxygen-dependent gene, showed significant expression alterations across three time points in epithelium (p=0.008), but not in stroma (p=0.66). Expression levels of VHL, STAT5B, and CYPA showed significant changes at the p<0.05 level in the stroma only. Effects of age, PSA, prostate size, Gleason score, surgery type, total surgery time, total ischemia time, and estimated blood loss on VEGF expression over time were not significant at the p<0.01 level. Therefore, surgical manipulation and tissue processing methods need to be taken into account when assessing prostatic biomarkers; however, resection does not dramatically alter mRNA profiles in prostate specimens.
Keywords: adult; clinical article; controlled study; human tissue; aged; human cell; laparoscopic surgery; genetic analysis; biological marker; prostate specific antigen; protein analysis; reverse transcription polymerase chain reaction; gene expression; bleeding; genetic transcription; prostate cancer; hypoxia; gleason score; ischemia; warm ischemia; messenger rna; prostatectomy; quantitative analysis; nucleotide sequence; prostate biopsy; operation duration; vasculotropin a; epithelium cell; minimally invasive surgery; stroma cell; hypoxia inducible factor 1alpha; urethra; von hippel lindau protein; sampling; microdissection; beta actin; gene expression analysis; tissue microdissection; 5 methyltetrahydrofolate homocysteine methyltransferase; cyclophilin a; lysosome associated membrane protein 2; rna 18s; stat5b protein; transferrin receptor; housekeeping gene
Journal Title: American Journal of Translational Research
Volume: 2
Issue: 3
ISSN: 1943-8141
Publisher: e-Century Publishing Corporation  
Date Published: 2010-01-01
Start Page: 210
End Page: 222
Language: English
PROVIDER: scopus
PMCID: PMC2892411
DOI/URL:

http://www.scopus.com/inward/record.url?eid=2-s2.0-77954674283&partnerID=40&md5=5f3c17c09c2226d3f5a0debb71a56ceb
Notes: --- - "Export Date: 20 April 2011" - "Source: Scopus"