Effect of surgical procedures on prostate tumor gene expression profiles

Abstract

Current surgical treatment of prostate cancer is typically accomplished by either open radical prostatectomy (ORP) or robotic-assisted laparoscopic radical prostatectomy (RALRP). Intra-operative procedural differences between the two surgical approaches may alter the molecular composition of resected surgical specimens, which are indispensable for molecular analysis and biomarker evaluation. The objective of this study is to investigate the effect of different surgical procedures on RNA quality and genome-wide expression signature. RNA integrity number (RIN) values were compared between total RNA samples extracted from consecutive LRP (n511) and ORP (n524) prostate specimens. Expression profiling was performed using the Agilent human whole-genome expression microarrays. Expression differences by surgical type were analyzed by Volcano plot analysis and gene ontology analysis. Quantitative reverse transcription (RT)-PCR was used for expression validation in an independent set of LRP (n58) and ORP (n58) samples. The LRP procedure did not compromise RNA integrity. Differential gene expression by surgery types was limited to a small subset of genes, the number of which was smaller than that expected by chance. Unexpectedly, this small subset of differentially expressed genes was enriched for those encoding transcription factors, oxygen transporters and other previously reported surgery-induced stress-response genes, and demonstrated unidirectional reduction in LRP specimens in comparison to ORP specimens. The effect of the LRP procedure on RNA quality and genome-wide transcript levels is negligible, supporting the suitability of LRP surgical specimens for routine molecular analysis. Blunted in vivo stress response in LRP specimens, likely mediated by CO 2 insufflation but not by longer ischemia time, is manifested in the reduced expression of stress-response genes in these specimens. Asian Journal of Andrology (2012) 14, 708-714; doi:10.1038/aja.2012.54; published online 6 August 2012Keywords: CO 2 insufflation; expression microarray; laparoscopic radical prostatectomy; open radical prostatectomy; prostate cancer; stress response INTRODUCTION Currently, for men with localized prostate cancer, surgical resection of the prostatic tumor is most often accomplished by one of two surgical approaches, open radical prostatectomy (ORP) or robot-assisted laparoscopic radical prostatectomy (RALRP), with the latter operation being increasingly practiced in developed countries. In the United States, RALRP accounts for an estimated 80% of RP surgeries. 1 In China, while RALRP is rarely performed, a substantial percentage of RP surgeries are nevertheless performed minimally invasively, via traditional laparoscopic radical prostatectomy (LRP). LRP is quite similar to RALRP and involves similar surgical approaches and steps that are different from conventional ORP. 2 The principal distinctions in sequential surgical steps between LRP and ORP are illustrated in Figure 1. During LRP, the prostate is typically devascularized earlier by ...

Biobanking of derivatives from radical retropubic and robot‐assisted laparoscopic prostatectomy tissues as part of the prostate cancer biorepository network

“…Hesitation towards the use of RALP‐derived biospecimens in prostate cancer research studies is centered on the fact that RALP specimens undergo a longer period of intra‐operative warm ischemia time. Interestingly, previous gene expression microarray studies on prostatectomy specimens exposed to longer periods of warm ischemia have demonstrated little variability in global gene expression patterns . As part of the growing trend towards RALP surgeries as opposed to RRP surgeries at our own institution and others, we aimed to assess the impact of the RALP procedure on known biomarkers of human prostate cancer, namely racemase, hepsin, ERG, TMPRSS2‐ERG fusions, and prostate‐cancer associated microRNAs.…”

Gene Panel Model Predictive of Outcome in Patients with Prostate Cancer

“…Candidate prognostic cancer models based on multiple gene panels or signatures have already been proposed (Idikio et al, 2011;Lossos et al, 2004;Ramaswamy et al, 2003;van de Vijver et al, 2002) including several for prostate cancer (Bismar et al, 2006;Cheville et al, 2008;Glinsky et al, 2004;Kosari et al, 2008;Li et al, 2012;Roobol et al, 2011;Ross et al, 2012;Singh et al, 2002).…”