910P - Molecular profiling of peripheral blood is associated with circulating tumor cells (CTCs) content and survival in metastatic castration-resistant pr...

Date 29 September 2012
Event ESMO Congress 2012
Session Poster presentation I
Topics Prostate Cancer
Translational Research
Presenter Lydia Gaba Garcia
Authors L. Gaba Garcia1, M. Marín-Aguilera2, J.J. Lozano3, A. Tagliapietra1, V. Ortega1, P. Gascón1, B. Mellado1
  • 1Medical Oncology, Hospital Clinic, 08036 - Barcelona/ES
  • 2Translational Oncology Laboratory, Hospital Clinic, 08036 - Barcelona/ES
  • 3Bioinformatics Platform, Ciberehd, Hospital Clinic, 08036 - Barcelona/ES

Abstract

Introduction

Detection of CTCs in peripheral blood has been demonstrated to correlate with clinical outcome in CRPC. The molecular characterization of these CTCs is essential for assessing genotypic features of mCRPC and should provide insights into the biology of tumor cell growth, invasion and metastasis.

Objective

To analyze the molecular profiling of peripheral blood from mCRPC patients with known CTC content and to identify those genes that may be related to the number of circulating cells and/or to the clinical outcome.

Material and methods

Peripheral blood from mCRPC patients was analyzed for CTC using the CellSearch System. Microarrays analysis was performed by the Human Gene 1.1 ST Array (Affymetrix) in samples with varing CTC content. Ten of the most differentially expressed genes between the < 5 and ≥ 5 CTCs groups were validated using reverse transcriptase PCR.

Results

43 patients were included. The median age was 71 years (42-88), the majority of patients had poor prognosis based on Gleason score (n = 22, 51.2%) and had recieved prior-docetaxel-based chemotherapy (n = 19, 44.2%). The median number of CTCs per patient sample was 59 (1-889), 23 patients (53.4%) presented < 5 CTCs and 20 patients (46.5%) had ≥ 5 CTCs. Overall survival (OS) in patients with ≥5 CTCs was significantly lower than those with <5 CTCs (P < 0.001). Global gene expression analysis identified the differential expression of 282 genes between samples with ≥5 CTCs vs <5 CTCs with 100 genes differentially expressed in patients with low overall survival. Gene expression of MMP8 and SELENBP1 provided the best gene combination for prediction of OS.

Conclusion

This exploratory study provides information about potential genes and pathways related with metastasis and poor prognosis. Further studies are necessary to validate the expression of MMP8 and SELENBP1 as predictors of low OS in mCRPC.

Disclosure

All authors have declared no conflicts of interest.