Dataset Information

Molecular profiling of peripheral blood is associated with circulating tumor cells content and poor survival in metastatic castration-resistant prostate cancer.

ABSTRACT: The enumeration of circulating tumor cells (CTCs) in peripheral blood correlates with clinical outcome in castration-resistant prostate cancer (CRPC). We analyzed the molecular profiling of peripheral blood from 43 metastatic CRPC patients with known CTC content in order to identify genes that may be related to prostate cancer progression. Global gene expression analysis identified the differential expression of 282 genes between samples with ?5 CTCs vs <5 CTCs, 58.6% of which were previously described as over-expressed in prostate cancer (18.9% in primary tumors and 56.1% in metastasis). Those genes were involved in survival functions such as metabolism, signal transduction, gene expression, cell growth, death, and movement. The expression of selected genes was evaluated by quantitative RT-PCR. This analysis revealed a two-gene model (SELENBP1 and MMP9) with a high significant prognostic ability (HR 6; 95% CI 2.61 - 13.79; P<0.0001). The combination of the two-gene signature plus the CTCs count showed a higher prognostic ability than CTCs enumeration or gene expression alone (P<0.05). This study shows a gene expression profile in PBMNC associated with CTCs count and clinical outcome in metastatic CRPC, describing genes and pathways potentially associated with CRPC progression.

SUBMITTER: Marin-Aguilera M

PROVIDER: S-EPMC4496379 | biostudies-literature | 2015 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Molecular profiling of peripheral blood is associated with circulating tumor cells content and poor survival in metastatic castration-resistant prostate cancer.

Marín-Aguilera Mercedes M Reig Òscar Ò Lozano Juan José JJ Jiménez Natalia N García-Recio Susana S Erill Nadina N Gaba Lydia L Tagliapietra Andrea A Ortega Vanesa V Carrera Gemma G Colomer Anna A Gascón Pedro P Mellado Begoña B

Oncotarget 20150401 12

The enumeration of circulating tumor cells (CTCs) in peripheral blood correlates with clinical outcome in castration-resistant prostate cancer (CRPC). We analyzed the molecular profiling of peripheral blood from 43 metastatic CRPC patients with known CTC content in order to identify genes that may be related to prostate cancer progression. Global gene expression analysis identified the differential expression of 282 genes between samples with ≥5 CTCs vs <5 CTCs, 58.6% of which were previously de ...[more]

PMID: 25871394

Similar Datasets

Project description:BackgroundMetastatic castration-resistant prostate cancer (mCRPC) is the lethal form of the disease. Several recent studies have identified genomic alterations in mCRPC, but the clinical implications of these genomic alterations have not been fully elucidated.ObjectiveTo use whole-genome sequencing (WGS) to assess the association between key driver gene alterations and overall survival (OS), and to use whole-transcriptome RNA sequencing to identify genomic drivers of enzalutamide resistance.Design, setting, and participantsWe performed survival analyses and gene set enrichment analysis (GSEA) on WGS and RNA sequencing results for a cohort of 101 mCRPC patients.Outcome measurements and statistical analysisOS was the clinical endpoint for all univariate and multivariable survival analyses. Candidate drivers of enzalutamide resistance were identified in an unbiased manner, and mutations of the top candidate were further assessed for enrichment among enzalutamide-resistant patients using Fisher's exact test.Results and limitationsHarboring two DNA alterations in RB1 was independently predictive of poor OS (median 14.1 vs 42.0mo; p=0.007) for men with mCRPC. GSEA identified the Wnt/β-catenin pathway as the top differentially modulated pathway among enzalutamide-resistant patients. Furthermore, β-catenin mutations were exclusive to enzalutamide-resistant patients (p=0.01) and independently predictive of poor OS (median 13.6 vs 41.7mo; p=0.025).ConclusionsThe presence of two RB1 DNA alterations identified in our WGS analysis was independently associated with poor OS among men with mCRPC. The Wnt/β-catenin pathway plays an important role in enzalutamide resistance, with differential pathway expression and enrichment of β-catenin mutations in enzalutamide-resistant patients. Moreover, β-catenin mutations were predictive of poor OS in our cohort.Patient summaryWe observed a correlation between genomic findings for biopsy samples from metastases from men with metastatic castration-resistant prostate cancer (mCRPC) and clinical outcomes. This work sheds new light on clinically relevant genomic alterations in mCRPC and provides a roadmap for the development of new personalized treatment regimens in mCRPC.

Dataset Information

Molecular profiling of peripheral blood is associated with circulating tumor cells content and poor survival in metastatic castration-resistant prostate cancer.

Publications

Molecular profiling of peripheral blood is associated with circulating tumor cells content and poor survival in metastatic castration-resistant prostate cancer.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure