Influence of Surgical Manipulation on Prostate Gene Expression: Implications for Molecular Correlates of Treatment Effects and Disease Prognosis

Author(s): Lin Daniel W, Coleman Ilsa M, Hawley Sarah, Dumpit Ruth, Gifford David, Kezele Philip, Hung Hau, Knudsen Beatrice S, Kristal Alan R, Nelson Peter S

Publication: Journal of Clinical Oncology, 2006, Vol. 24, Page 3763

PubMed ID: 16822846 PubMed Review Paper? No

Purpose of Paper

Conclusion of Paper

Studies

1. Study Purpose

   The purpose of this study was to determine if gene expression, as measured by cDNA microarray, is altered following surgical resection. Biospies were collected in situ from the prostate prior to vascular clamp placement or ex vivo after radical prostatectomy in twelve patients.

   Summary of Findings:

   Of the 5,753 cDNAs examined by cDNA microarray, 88 cDNAs representing 62 genes were altered in biopsies obtained from surgically resected specimens compared to biopsies procured in situ prior to vascular clamp placement. The false-discovery rate was estimated to be approximately 10%. Affected genes included several that are involved in acute phase response, IER2 and JUNB, cell proliferation regulation, P21Cip1 and KLF6, as well as those associated with the JNK stress-response pathway. No transcripts exhibiting a significant reduction in expression following surgical resection were observed.

   Biospecimens

   • Tissue - Prostate

   Preservative Types

   • OCT

   Diagnoses:

   • Neoplastic - Carcinoma

   Platform:

   Analyte	Technology Platform
   RNA	DNA microarray

   Pre-analytical Factors:

   Classification	Pre-analytical Factor	Value(s)
   Biospecimen Acquisition	Method of tissue acquisition	Biopsy Surgical resection

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2. Study Purpose

   The purpose of this study was to determine if expression of a subset of genes identified by microarray (of DUSP1, KLF6, and AMACR) in fact differ among case-matched biopsy specimens procured in situ before vascular clamp placement or ex vivo after radical prostatectomy. A total of 8 cores were obtained from each of the 12 patients assessed.

   Summary of Findings:

   Quantitative RT-PCR (qRT-PCR) analysis revealed that DUSP1 and KLF6 expression were significantly upregulated, by 14- and 4-fold respectively, in biopsy specimens procured after surgical resection compared to those collected before vascular clamp placement. AMACAR expression did not differ significantly among biopsy specimens collected pre-and post-resection. QRT-PCR results are consistent with those reported for microarray.

   Biospecimens

   • Tissue - Prostate

   Preservative Types

   • OCT

   Diagnoses:

   • Neoplastic - Carcinoma

   Platform:

   Analyte	Technology Platform
   RNA	Real-time qRT-PCR

   Pre-analytical Factors:

   Classification	Pre-analytical Factor	Value(s)
   Real-time qRT-PCR Specific	Targeted nucleic acid	DUSP1 KLF6 AMACR
   Biospecimen Acquisition	Method of tissue acquisition	Biopsy Surgical resection

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3. Study Purpose

   The purpose of this study was to examine the potential influence of patient-related variables (including patient age, prostate gland volume, prostate-specific antigen concentration), and surgery-related factors (including warm ischemia time, estimated blood loss amount, and surgical duration) on gene expression as measured by microarray. Microarray analysis was limited to a subset of 62 genes that displayed differential expression as a result of time of procurement, pre- versus post-surgical resection. Four core biopsies were obtained from each of the 12 patients assessed before vascular clamp placement and again after completion of a radical prostatectomy.

   Summary of Findings:

   Statistically relevant correlations between clinical and operative variables and gene expression were limited to prostate gland volume. The magnitude of change induced by surgical resection when compared to biopsies taken in situ was negatively correlated to prostate gland volume for 55 (or 89%) of the 62 genes examined, translating to smaller differences in transcript expression for larger prostate gland volumes. Conversely, age, PSA concentration, total operative time, warm ischemia time, and estimated blood loss were not associated with differences in gene expression, although statistical power was modest.

   Biospecimens

   • Tissue - Prostate

   Preservative Types

   • OCT

   Diagnoses:

   • Neoplastic - Carcinoma

   Platform:

   Analyte	Technology Platform
   RNA	DNA microarray

   Pre-analytical Factors:

   Classification	Pre-analytical Factor	Value(s)
   Preaquisition	Blood loss amount	450 ml 600 ml 650 ml 700 ml 800 ml 950 ml 1000 ml 1100 ml 1500 ml 1600 ml 2100 ml
   Preaquisition	Warm ischemia time	19 min 20 min 25 min 26 min 27 min 29 min 30 min 33 min 35 min 36 min 40 min
   Preaquisition	Patient age	53 59 60 62 64 65 67 68 69
   Preaquisition	Biomarker level	2.5 ng/dL 3.5 ng/dL 4.2 ng/dL 4.6 ng/dL 4.7 ng/dL 5.0 ng/dL 5.4 ng/dL 5.6 ng/dL 6.3 ng/dL 8.2 ng/dL 16.0 ng/dL
   Preaquisition	Surgery duration	164 min 176 min 180 min 185 min 187 min 196 min 201 min 203 min 210 min 221 min 237 min
   Biospecimen Acquisition	Organ measurements	Prostate gland volume (31 ml) 35 ml 36 ml 37 ml 39 ml 43 ml 49 ml 50 ml 65 ml 78 ml 149 ml

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