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Prostate cancer genomics – identification of prognostic markers from the bone marrow

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Sources of Funding: none

Introduction

Disseminated tumor cells (DTC) can be detected in the bone marrow of a high proportion of patients with prostate cancer. The prognostic value of these DTCs, however, remains a matter of debate. Moreover, robust DTC-specific biomarker are not yet identified. The aim of this study was to evaluate gene expression differences in bone marrow derived from patients with early tumor recurrence after radical prostatectomy (RP) and patients without recurrence, respectively.

Methods

The initial discovery cohort of patients was subdivided into two groups: one with early recurrence after RP and one without recurrence. All patients underwent intraoperative bone marrow (BM) aspiration biopsy. RNA was isolated from nine BM biopsies of each cohort using the PAXgene RNA isolation kit. To identify differently expressed genes the TaqMan® OpenArray® Human cancer panel was used. Identified genes were further validated in a validation cohort encompassing 30 BM biopsies for each group. Quantitative PCR was performed to evaluate the significance of previously identified differentially expressed genes.

Results

Of 245 patients with intraoperative BM biopsy nine patients showed an early recurrence within two years after RP. We correlated the results with nine patients with high risk PC (Gleason ? 8) and no recurrence within five years after RP. Altogether, 13 overexpressed and two downregulated genes in the recurrence group were identified. The validation with 58 patients resulted in a significant overexpression of CHPT1 (p=.0029), MYC (p<.0001), MCM6 (p<.0001) and CTNNB1 (p<.0001).

Conclusions

For the first time, gene expression profiling of BM biopsies from patients with recurrence after RP was performed. In this single-center cohort of patients with recurrence after radical prostatectomy CHPT1, MYC, MCM6 and CTNNB1 were significantly overexpressed compared to a cohort without recurrence after RP. Thus, our data implicate a predictive valence of target genes MYC, CTNNB1, MCM6 and CHPT1 with regard to prostate cancer recurrence after RP.

Funding

none

Authors
Simone Bier
Jörg Hennenlotter
Ursula Haerle
Eleni Karpatsi
Arnulf Stenzl
Tilman Todenhöfer
Christian Schmees
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