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. 2023 Feb 14:13:1053111.
doi: 10.3389/fonc.2023.1053111. eCollection 2023.

The positive relationship between androgen receptor splice variant-7 expression and the risk of castration-resistant prostate cancer: A cumulative analysis

Shankun Zhao  1 , Jian Liao  2 , Shilong Zhang  3 , Maolei Shen  1 , Xin Li  1 , Libo Zhou  4
Affiliations

The positive relationship between androgen receptor splice variant-7 expression and the risk of castration-resistant prostate cancer: A cumulative analysis

Shankun Zhao et al. Front Oncol. .

Abstract

Background: At present, androgen deprivation therapy (ADT) is still the standard regimen for patients with metastatic and locally advanced prostate cancer (PCa). The level of androgen receptor splice variant-7 (AR-V7) in men with castration-resistant prostate cancer (CRPC) has been reported to be elevated compared with that in patients diagnosed with hormone-sensitive prostate cancer (HSPC).

Aim: Herein, we performed a systematic review and cumulative analysis to evaluate whether the expression of AR-V7 was significantly higher in patients with CRPC than in HSPC patients.

Methods: The commonly used databases were searched to identify the potential studies reporting the level of AR-V7 in CRPC and HSPC patients. The association between CRPC and the positive expression of AR-V7 was pooled by using the relative risk (RR) with the corresponding 95% confidence intervals (CIs) under a random-effects model. For detecting the potential bias and the heterogeneity of the included studies, sensitivity analysis and subgroup analysis were performed. Publication bias was assessed Egger's and Begg's tests. This study was registered on PROSPERO (ID: CRD42022297014).

Results: This cumulative analysis included 672 participants from seven clinical trials. The study group contained 354 CRPC patients, while the other group contained 318 HSPC patients. Pooled results from the seven eligible studies showed that the expression of positive AR-V7 was significantly higher in men with CRPC compared to those with HSPC (RR = 7.55, 95% CI: 4.61-12.35, p < 0.001). In the sensitivity analysis, the combined RRs did not change substantially, ranging from 6.85 (95% CI: 4.16-11.27, p < 0.001) to 9.84 (95% CI: 5.13-18.87, p < 0.001). In the subgroup analysis, a stronger association was detected in RNA in situ hybridization (RISH) measurement in American patients, and those studies were published before 2011 (all p < 0.001). There was no significant publication bias identified in our study.

Conclusion: Evidence from the seven eligible studies demonstrated that patients with CRPC had a significantly elevated positive expression of AR-V7. More investigations are still warranted to clarify the association between CRPC and AR-V7 testing.

Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42022297014.

Keywords: androgen receptor variant-7; castration-resistant prostate cancer; cumulative analysis; expression; systematic review.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Flowchart of study selection.
Figure 2
Figure 2
Forest plots of meta-analysis of the included studies on the association between CRPC and positive expression of AR-V7. CRPC, castration-resistant prostate cancer.
Figure 3
Figure 3
Sensitivity analysis after each study was excluded by turns.
Figure 4
Figure 4
Eggers test to detect publication bias.
Figure 5
Figure 5
Beggs test to detect publication bias.
See this image and copyright information in PMC

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