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

Marín-Aguilera M, Reig Ò, Lozano JJ, Jiménez N, García-Recio S, Erill N, Gaba L, Tagliapietra A, Ortega V, Carrera G, Colomer A, Gascón P, Mellado B - Oncotarget (2015)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Translational Genomics Group and Targeted Therapeutics in Solid Tumors Group, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.

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.

No MeSH data available.


Related in: MedlinePlus

Receiver operating characteristic (ROC) curves illustrating CTCs count and two-gene signature (MMP9+SELENBP1) alone and combined for the prediction of OS
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Figure 5: Receiver operating characteristic (ROC) curves illustrating CTCs count and two-gene signature (MMP9+SELENBP1) alone and combined for the prediction of OS

Mentions: The combination of SELENBP1 and MMP9 gene expression data was the best gene signature to indicate poorer prognosis, since elevated expression of both markers significantly correlated with a lower OS (Fig. 4). The predictive accuracy of the two-gene signature for OS was assessed by the ROC curve (AUC: 0.79) (Fig. 5). Taking into account the whole series of patients (N=70), the predictive accuracy of the two-gene expression model was similar than in the subset of 43 initial patients (AUC: 0.77; data not shown).


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

Marín-Aguilera M, Reig Ò, Lozano JJ, Jiménez N, García-Recio S, Erill N, Gaba L, Tagliapietra A, Ortega V, Carrera G, Colomer A, Gascón P, Mellado B - Oncotarget (2015)

Receiver operating characteristic (ROC) curves illustrating CTCs count and two-gene signature (MMP9+SELENBP1) alone and combined for the prediction of OS
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4496379&req=5

Figure 5: Receiver operating characteristic (ROC) curves illustrating CTCs count and two-gene signature (MMP9+SELENBP1) alone and combined for the prediction of OS
Mentions: The combination of SELENBP1 and MMP9 gene expression data was the best gene signature to indicate poorer prognosis, since elevated expression of both markers significantly correlated with a lower OS (Fig. 4). The predictive accuracy of the two-gene signature for OS was assessed by the ROC curve (AUC: 0.79) (Fig. 5). Taking into account the whole series of patients (N=70), the predictive accuracy of the two-gene expression model was similar than in the subset of 43 initial patients (AUC: 0.77; data not shown).

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Translational Genomics Group and Targeted Therapeutics in Solid Tumors Group, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.

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.

No MeSH data available.


Related in: MedlinePlus