Overexpression of certain transient receptor potential and Orai channels in prostate cancer is associated with decreased risk of systemic recurrence after radical prostatectomy
Corresponding Author
M. A. Perrouin-Verbe MD, PhD
Department of Urology, CHRU-Université de Brest, Brest, France
INSERM UMR1078, Université de Bretagne Occidentale, Brest, France
Department of Urology, CHU-Université de Nantes, Nantes, France
Correspondence Marie-Aimée Perrouin-Verbe, MD, PhD, Department of Urology, CHU-Université de Nantes 1 place Alexis Ricordeau, 44000 Nantes, France.
Email: [email protected]
Search for more papers by this authorN. Schoentgen MD
Department of Urology, CHRU-Université de Brest, Brest, France
INSERM UMR1078, Université de Bretagne Occidentale, Brest, France
Search for more papers by this authorM. Talagas MD, PhD
Department of Pathology, CHRU-Université de Brest, Brest, France
EA 4685 – LIEN, Université de Bretagne Occidentale, Brest, France
Search for more papers by this authorR. Garlantezec MD, PhD
INSERM UMR1085-IRSET, Université Rennes 1, Rennes, France
Search for more papers by this authorA. Uguen MD, PhD
Department of Pathology, CHRU-Université de Brest, Brest, France
Search for more papers by this authorL. Doucet MD
Department of Pathology, CHRU-Université de Brest, Brest, France
Search for more papers by this authorS. Rosec
INSERM UMR1412, Centre d’Investigation Clinique, CHRU-Université de Brest, Brest, France
Search for more papers by this authorP. Marcorelles MD, PhD
Department of Pathology, CHRU-Université de Brest, Brest, France
Search for more papers by this authorM. Potier-Cartereau PhD
INSERM UMR1069, Université François Rabelais, Tours, France
Search for more papers by this authorC. Vandier PhD
INSERM UMR1069, Université François Rabelais, Tours, France
Search for more papers by this authorC. Ferec MD, PhD
INSERM UMR1078, Université de Bretagne Occidentale, Brest, France
Search for more papers by this authorG. Fromont MD, PhD
INSERM UMR1069, Université François Rabelais, Tours, France
Department of Pathology, CHRU-Université de Tours, Tours, France
Search for more papers by this authorG. Fournier MD
Department of Urology, CHRU-Université de Brest, Brest, France
Search for more papers by this authorA. Valeri MD, PhD
Department of Urology, CHRU-Université de Brest, Brest, France
Search for more papers by this authorO. Mignen PhD
INSERM UMR1078, Université de Bretagne Occidentale, Brest, France
INSERM UMR1227, Université de Bretagne Occidentale, Brest, France
Search for more papers by this authorCorresponding Author
M. A. Perrouin-Verbe MD, PhD
Department of Urology, CHRU-Université de Brest, Brest, France
INSERM UMR1078, Université de Bretagne Occidentale, Brest, France
Department of Urology, CHU-Université de Nantes, Nantes, France
Correspondence Marie-Aimée Perrouin-Verbe, MD, PhD, Department of Urology, CHU-Université de Nantes 1 place Alexis Ricordeau, 44000 Nantes, France.
Email: [email protected]
Search for more papers by this authorN. Schoentgen MD
Department of Urology, CHRU-Université de Brest, Brest, France
INSERM UMR1078, Université de Bretagne Occidentale, Brest, France
Search for more papers by this authorM. Talagas MD, PhD
Department of Pathology, CHRU-Université de Brest, Brest, France
EA 4685 – LIEN, Université de Bretagne Occidentale, Brest, France
Search for more papers by this authorR. Garlantezec MD, PhD
INSERM UMR1085-IRSET, Université Rennes 1, Rennes, France
Search for more papers by this authorA. Uguen MD, PhD
Department of Pathology, CHRU-Université de Brest, Brest, France
Search for more papers by this authorL. Doucet MD
Department of Pathology, CHRU-Université de Brest, Brest, France
Search for more papers by this authorS. Rosec
INSERM UMR1412, Centre d’Investigation Clinique, CHRU-Université de Brest, Brest, France
Search for more papers by this authorP. Marcorelles MD, PhD
Department of Pathology, CHRU-Université de Brest, Brest, France
Search for more papers by this authorM. Potier-Cartereau PhD
INSERM UMR1069, Université François Rabelais, Tours, France
Search for more papers by this authorC. Vandier PhD
INSERM UMR1069, Université François Rabelais, Tours, France
Search for more papers by this authorC. Ferec MD, PhD
INSERM UMR1078, Université de Bretagne Occidentale, Brest, France
Search for more papers by this authorG. Fromont MD, PhD
INSERM UMR1069, Université François Rabelais, Tours, France
Department of Pathology, CHRU-Université de Tours, Tours, France
Search for more papers by this authorG. Fournier MD
Department of Urology, CHRU-Université de Brest, Brest, France
Search for more papers by this authorA. Valeri MD, PhD
Department of Urology, CHRU-Université de Brest, Brest, France
Search for more papers by this authorO. Mignen PhD
INSERM UMR1078, Université de Bretagne Occidentale, Brest, France
INSERM UMR1227, Université de Bretagne Occidentale, Brest, France
Search for more papers by this authorThis work was performed at INSERM UMR1078, Université de Bretagne Occidentale and at the Department of Urology, CHRU-Université de Brest, 29200 Brest, France.
Abstract
Background: Several studies had suggested the potential role of calcium signaling in prostate cancer (PCa) prognosis and agressiveness. We aimed to investigate selected proteins contributing to calcium (Ca2+) signaling, (Orai, stromal interaction molecule (STIM), and transient receptor potential (TRP) channels) and involved in cancer hallmarks, as independent predictors of systemic recurrence after radical prostatectomy (RP).
Methods: A case-control study including 112 patients with clinically localized PCa treated by RP between 2002 and 2009 and with at least 6-years’ follow-up. Patients were divided into two groups according to the absence or presence of systemic recurrence. Expression levels of 10 proteins involved in Ca2+ signaling (TRPC1, TRPC4, TRPV5, TRPV6, TRPM8, STIM1, STIM2, Orai1, Orai2, and Orai3), were assessed by immunohistochemistry using tissue microarrays (TMAs) constructed from paraffin-embedded PCa specimens. The level of expression of the various transcripts in PCa was assessed using quantitative polymerase chain reaction (qPCR) analysis. RNA samples for qPCR were obtained from fresh frozen tissue samples of PCa after laser capture microdissection on RP specimens. Relative gene expression was analyzed using the method.
Results: Multivariate analysis showed that increased expression of TRPC1, TRPC4, TRPV5, TRPV6, TRPM8, and Orai2 was significantly associated with a lower risk of systemic recurrence after RP, independently of the prostate-specific antigen (PSA) level, percentage of positive biopsies, and surgical margin (SM) status (P = .007, P = .01, P < .001, P = .0065, P = .007, and P = .01, respectively). For TRPC4, TRPV5, and TRPV6, this association was also independent of Gleason score and pT stage. Moreover, overexpression of TRPV6 and Orai2 was significantly associated with longer time to recurrence after RP (P = .048 and .023, respectively). Overexpression of TRPC4, TRPV5, TRPV6, and Orai2 transcripts was observed in group R− (3.71-, 5.7-, 1.14-, and 2.65-fold increase, respectively).
Conclusions: This is the first study to suggest the independent prognostic value of certain proteins involved in Ca2+ influx in systemic recurrence after RP: overexpression of TRPC1, TRPC4, TRPV5, TRPV6, TRPM8, and Orai2 is associated with a lower risk of systemic recurrence. TRPC4, TRPV5, and TRPV6 appear to be particularly interesting, as they are independent of the five commonly used predictive factors, that is, PSA, percentage of positive biopsies, SM status, Gleason score, and pT stage.
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