Circulating Androgen Receptor for Prognosis and Treatment Selection in Prostate Cancer

Conteduca, Vincenza; Wetterskog, Daniel; González-Billalabeitia, Enrique; Brighi, Nicole; Giorgi, Ugo De; Attard, Gerhardt

doi:10.1016/j.euo.2020.12.009

Cited by 9 publications

(6 citation statements)

References 25 publications

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“…growth, differentiation and malignant transformation of prostate epithelial cells, which is closely related to the occurrence and development of PCa (24)(25)(26). At present, AR is involved in the proliferation, differentiation, invasion, metastasis and immune escape of PCa (24)(25)(26).…”

Section: Discussionmentioning

confidence: 99%

The involvement of high succinylation modification in the development of prostate cancer

Zhang

Chen²,

Fang³

et al. 2022

Front. Oncol.

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ObjectiveSuccinylation modification of the lysine site plays an important role in tumorigenesis and development, but it is rarely reported in prostate cancer (PCa), so this study aims to elucidate its expression in and clinical correlation with PCa.MethodsA total of 95 tumor, 3 normal and 52 paired adjacent tissue of PCa were involved for succinylation stanning. 498 PCa samples with 20 succinylation modification-related genes from TCGA were downloaded for model construction. Statistical methods were employed to analyze the data, including Non-Negative Matrix Factorization (NMF) algorithm, t-Distributed Stochastic Neighbor Embedding (t-SNE) algorithm and Cox regression analysis.ResultsThe pan-succinyllysine antibody stanning indicated that tumor tissues showed higher succinyllysine level than adjacent tissues (p<0.001). Gleason grade and PDL1 expression levels were significantly different (p<0.001) among the high, medium and low succinylation staining scores. The types of PCa tissue were divided into four clusters using RNA-seq data of 20 succinylation-related genes in TCGA database. Clinical characterize of age, PSA level, and pathological stage showed differences among four clusters. The expression of succinylation-related genes (KAT5, SDHD and GLYATL1) and PCa related genes (PDL1, AR and TP53) were significantly different in 52 matched tumor and adjacent tissues (p<0.001). GLYATL1 and AR gene expression was significantly related to the pathological stage of PCa.ConclusionSuccinylation was significantly increased in PCa tissues and was closely related to Gleason grade and PD-L1 expression. Model construction of 20 genes related to succinylation modification showed that the later the pathological stage of PCa, the higher the level of succinylation modification.

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Section: Discussionmentioning

confidence: 99%

The involvement of high succinylation modification in the development of prostate cancer

Zhang

Chen²,

Fang³

et al. 2022

Front. Oncol.

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“…Second, unlike the PROfound trial, we used the ctDNA rather than tumor tissue to identify HRR genotyping. However, HRR gene status was found to be concordant between serial ctDNA‐positive sample collected in the mCRPC setting and archival primary tissue taken at cancer diagnosis [ 41 , 42 ]. In addition, the ctDNA% in our cohort was low due to the low PSA level at enrolment.…”

Section: Discussionmentioning

confidence: 99%

The prevalence and prognosis of next‐generation therapeutic targets in metastatic castration‐resistant prostate cancer

Pan

Zhao

et al. 2022

Molecular Oncology

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The success of the PROfound, IPATential150, and TheraP trials promoted the transition from sequential treatment to therapeutic targets (TTs)‐guided precision treatment in metastatic castration‐resistant prostate cancer (mCRPC). The objective of this study was to evaluate the prevalence and prognostic value of TTs from these three trials. All included Chinese mCRPC patients underwent circulating tumor DNA (ctDNA) sequencing, PTEN status assessment, and dual‐tracer [68Ga‐prostate‐specific membrane antigen (PSMA) and 18F‐fluorodexyglucose (FDG)] positron emission tomography/computed tomography (PET/CT). Previous treatment with cabazitaxel, Lu‐PSMA or olaparib was unallowed. Patients with known significant sarcomatoid or spindle cell or neuroendocrine small cell components were also excluded. TTs were defined as positive as follows: (a) high PSMA and no PSMA−/FDG+ disease on dual‐tracer PET/CT scans; (b) defects in homologous recombination repair (HRR) genes in ctDNA; and (c) loss of PTEN immunohistochemistry staining in tumor tissue. The prevalence and prognostic value on progression‐free survival (PFS) of TTs were evaluated. A total of 106 consecutive mCRPC patients were included. The prevalence of positive PET/CT, HRR defect, and PTEN loss was 30%, 29% and 16%, respectively. Sixty‐three patients had at least one TT. Metastatic volume (odds ratio = 5.0; P = 0.017) was the only independent factor of positive TT in multivariate analysis. Seventy‐four patients received abiraterone after TT screening. Patients with positive PET/CT (P = 0.011) and HRR defect (P = 0.002) had a significantly shorter PFS after receiving abiraterone than patients with negative TTs. However, PTEN status was unrelated to PFS, which may be due to a less number of patients with PTEN loss (P = 0.952). Overall, patients with any positive TTs had a significantly shorter PFS after abiraterone than patients with negative TTs (P = 0.009). Nearly 60% of Chinese patients with mCRPC who had a poor prognosis on abiraterone were candidates for precision treatments based on the specific criteria of TTs.

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“…Taking into account preliminary data and previous studies in mCRPC patients, we estimated a 30% prevalence of AR alterations. 17 , 18 Using these parameters, the power analysis identified that a total sample size of 40 patients and 40 events (death) would be required to achieve adequate statistical power. 19 , 20 …”

Section: Methodsmentioning

confidence: 99%

Longitudinal assessment of plasma androgen receptor copy number predicts overall survival in subsequent treatment lines in castration-resistant prostate cancer: analysis from a prospective trial

Brighi,

Conteduca,

Gurioli

et al. 2023

ESMO Open

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Circulating Androgen Receptor for Prognosis and Treatment Selection in Prostate Cancer

Cited by 9 publications

References 25 publications

The involvement of high succinylation modification in the development of prostate cancer

The involvement of high succinylation modification in the development of prostate cancer

The prevalence and prognosis of next‐generation therapeutic targets in metastatic castration‐resistant prostate cancer

Longitudinal assessment of plasma androgen receptor copy number predicts overall survival in subsequent treatment lines in castration-resistant prostate cancer: analysis from a prospective trial

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