Plasma androgen receptor and serum chromogranin A in advanced prostate cancer

Conteduca, Vincenza; Scarpi, Emanuela; Salvi, Samanta; Casadio, Valentina; Lolli, Cristian; Gurioli, Giorgia; Schepisi, Giuseppe; Wetterskog, Daniel; Farolfi, Alberto; Menna, Cecilia; Lisi, Delia De; Burgio, Salvatore Luca; Beltran, Himisha; Attard, Gerhardt; Giorgi, Ugo De

doi:10.1038/s41598-018-33774-4

Cited by 24 publications

(39 citation statements)

References 47 publications

(63 reference statements)

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Section: Discussionsupporting

confidence: 90%

“…In this study, data on the impact of AR on outcomes of patients treated with taxanes were not available at the time of the analysis; however, a recent retrospective analysis did not show a prognostic role of AR aberrations in patients treated with docetaxel, reinforcing the importance of these aberrations only for abiraterone and enzalutamide …”

Section: Discussionmentioning

confidence: 80%

“…Our data analysis confirmed the negative prognostic and predictive impact of copy number alterations of the AR gene for both abiraterone and enzalutamide groups of patients, as already described in literature. 10,[13][14][15][16] Patients treated with enzalutamide with testosterone below the median value have a worse PFS and OS, while the difference was not significant for patients treated with abiraterone. The mechanism of action of enzalutamide could explain these results.…”

Section: Discussionmentioning

confidence: 98%

“…In addition, we performed AR copy number with QuantStudio3D digital PCR system (Life Technologies, Carlsbad, CA) using ElF2C1 and RNase or a digital droplet polymerase chain reaction (ddPCR) assay was optimized for the evaluation of AR copy number, using three reference genes: NSUN3, ElF2C1, and AP3B1, and ZXDB at Xp11.21 as a control gene not involving the whole arm of chromosome. Each PCR reaction was prepared with 1 to 2 ng DNA and partitioned into ~20 000 droplets per sample.…”

Section: Methodsmentioning

confidence: 99%

“…In addition, we performed AR copy number with QuantStudio3D digital PCR system (Life Technologies, Carlsbad, CA) using ElF2C1 and RNase 10,12 or a digital droplet polymerase chain reaction (ddPCR) assay [13][14][15] was optimized for the evaluation of AR copy number, using three reference genes: NSUN3, ElF2C1, and AP3B1, and ZXDB at Xp11.21 as a control gene not involving the whole arm This assay is based on a competitive test principle using a highaffinity monoclonal antibody (sheep) specifically directed against testosterone. Endogenous testosterone released from the sample by 2-bromo estradiol competes with the added testosterone derivative labeled with a ruthenium complex; finally, the complex becomes bound to the solid phase via interaction of biotin and streptavidin.…”

Section: Copy Number Gain Of Ar and Testosterone Analysis In A Bloomentioning

confidence: 99%

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Testosterone levels and androgen receptor copy number variations in castration‐resistant prostate cancer treated with abiraterone or enzalutamide

et al. 2019

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Purpose Our study aims to investigate the association between copy number of the androgen receptor (AR) and testosterone levels in metastatic castration‐resistant prostate cancer (mCRPC) treated with second‐generation antiandrogen therapies. Materials and Methods We retrospectively collected data from mCRPC treated with abiraterone acetate and enzalutamide. Serum testosterone levels were collected at baseline, at 3 months since the start of therapy and at disease progression. A cohort of cases treated with docetaxel was also used to evaluate the impact of testosterone levels. Results Patients treated with abiraterone with AR copy number aberrations and basal testosterone levels below 0.09 nmol/L had worse progression‐free survival (PFS) compared to patients with no AR copy number abnormalities (8.5 vs 2.9 months, P = 0.005). No relevant differences were observed in the enzalutamide group with a PFS of 3.9 months (no AR gain) vs 2.7 months ( AR gain, P = 0.004) for patients with below 0.09 nmol/L testosterone levels. Similar results are obtained for univariate analysis for overall survival (OS). The negative prognostic role of AR copy number gain in OS for both treatment groups (25.5 vs 10.6 months, P = 0.0002 for abiraterone and 14.1 vs 8.3 months, P = 0.031 for enzalutamide) was confirmed, and it was recognized the negative prognostic impact of testosteronemia below 0.09 only for patients treated with enzalutamide (8.8 vs 42.8 months, P = 0.016). On multivariate analysis for patients treated with abiraterone, low testosterone levels below 0.09 and plasma AR gain were significantly associated with worse PFS and OS. These data are confirmed in the enzalutamide group for PFS. Conclusions Testosterone levels and the AR copy number alterations were considered as independent prognostic factors. The results of this study show that serum testosteronemia associated with changes in copy number of AR gene could represent a noninvasive biomarker useful to identify a subgroup of patients with worse prognosis that can benefit less from second‐generation antiandrogen therapies in the mCRPC setting.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 80%

Section: Discussionmentioning

confidence: 98%

Section: Methodsmentioning

confidence: 99%

Section: Copy Number Gain Of Ar and Testosterone Analysis In A Bloomentioning

confidence: 99%

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Testosterone levels and androgen receptor copy number variations in castration‐resistant prostate cancer treated with abiraterone or enzalutamide

et al. 2019

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Association between lactate dehydrogenase levels and oncologic outcomes in metastatic prostate cancer: A meta‐analysis

et al. 2020

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Plasma progastrin‐releasing peptide level shows different predictive profiles for treatment response by androgen receptor axis‐targeted agents in patients with metastatic castration‐resistant prostate cancer

et al. 2022

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Background: The neuroendocrine (NE) pathway cannot be ignored as a mechanism for castration-resistant prostate cancer (CRPC) progression. The neuromediator, gastrin-releasing peptide (GRP) may be involved in the aberrant activation of the normal androgen receptor (AR) and increased AR variants. This study focused on plasma levels of progastrin-releasing peptide (ProGRP) and examined the treatment outcomes with androgen receptor axis-targeted (ARAT) agents.Methods: One hundred patients with metastatic CRPC were enrolled. Enzalutamide (ENZ) or abiraterone acetate/prednisone (AA/P) were administered to 50 patients each in a nonrandomized manner as a first-line or later choice. Plasma ProGRP levels were determined using a chemiluminescent enzyme immunoassay, and data were collected prospectively. The study endpoints were prostate-specific antigen (PSA) response and survival estimates.Results: In the ENZ series, ProGRP levels correlated with the maximum PSA change from baseline (high ProGRP: À34.5% vs. low ProGRP: À85.7% p = .033). PSA progression-free survival (PFS), radiographic/symptomatic (r/s) PFS, and overall survival (OS) in patients with high ProGRP were significantly worse than those in patients with low ProGRP (median PSA-PFS: 3.3 vs. 10.0 months, p = .001, r/s PFS: 5.0 vs. 15.0 months, p < 0.001, and OS 17.5 vs. 49.0 months, p < .001, respectively).In addition, ProGRP showed an independent predictive value for all survival estimates in multivariate analyses. In the AA/P series, ProGRP levels did not correlate with the PSA change or predict PSA-PFS and r/s PFS, but they maintained a significant difference in OS (19.0 vs. 48.0 months, p = .003).Conclusions: Plasma ProGRP provides a consistent predictive value for OS in metastatic CRPC patients who underwent therapy with ARAT agents. Meanwhile, ProGRP showed different predictive profiles for PSA-and r/s PFS between ENZ and

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Plasma androgen receptor and serum chromogranin A in advanced prostate cancer

Cited by 24 publications

References 47 publications

Testosterone levels and androgen receptor copy number variations in castration‐resistant prostate cancer treated with abiraterone or enzalutamide

Testosterone levels and androgen receptor copy number variations in castration‐resistant prostate cancer treated with abiraterone or enzalutamide

Association between lactate dehydrogenase levels and oncologic outcomes in metastatic prostate cancer: A meta‐analysis

Plasma progastrin‐releasing peptide level shows different predictive profiles for treatment response by androgen receptor axis‐targeted agents in patients with metastatic castration‐resistant prostate cancer

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