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. 2023 Sep;43(9):4023-4030.
doi: 10.21873/anticanres.16590.

GNRH2 Polymorphism in Men With Prostate Cancer Treated With Androgen Deprivation Therapy

Tristan M Sissung  1 , Sarah Lochrin  1 , Tyler Liu  1 , Keith Schmidt  1 , Jonathan Strope  2 , Emily Risdon  2 , Hyoyoung Choo-Wosoba  3 , David J Venzon  3 , Wiem Lassoued  4 , Houssein A Sater  4 , Beatriz Walter-Rodriguez  4 , Douglas K Price  2 , William D Figg  5   2   4
Affiliations

GNRH2 Polymorphism in Men With Prostate Cancer Treated With Androgen Deprivation Therapy

Tristan M Sissung et al. Anticancer Res. 2023 Sep.

Abstract

Background/aim: Gonadotropin-releasing hormone 2 (GNRH2) is a poorly-studied peptide hormone that is widely distributed in the central nervous system and expressed in peripheral tissues of mammals. The non-synonymous rs6051545 variant in GNRH2 (A16V) has been linked to higher serum testosterone concentrations. This study investigated whether the A16V variant is associated with altered androgen-deprivation therapy (ADT) progression-free survival (PFS) and overall survival (OS).

Patients and methods: We examined the expression of GNRH2 in prostate tissue microarrays comprising normal tissue, prostatic hyperplasia, and prostate cancer using immunofluorescence. We also evaluated the GNRH2 genotype in 131 patients with prostate cancer who received ADT and compared PFS and OS between the variant and wild-type genotypes.

Results: GNRH2 was detected in all prostate tissues, although expression did not vary with Gleason grade or disease stage (p=0.71). The GNRH2 A16V genotype was not associated with PFS or OS; however, univariate and multivariate analyses revealed Gleason score and definitive local therapy were each associated with PFS (p≤0.0074), whereas age and Gleason score were associated with OS (p≤0.0046).

Conclusion: GNRH2 is expressed in normal, hyperplastic, and neoplastic prostate tissues; the A16V variant is not related to treatment outcome or survival.

Keywords: GNRH2; androgen deprivation therapy; prostate cancer; survival.

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Conflict of interest statement

Conflicts of Interest

The Authors declare no conflicts of interest in relation to this study.

Figures

Figure 1.
Figure 1.
Immunofluorescence was conducted on prostate tissue microarrays using a GNRH2-specific antibody. (A) Representative images of GNRH2 expression are presented for normal prostate, prostatic hyperplasia, prostatectomy tissue (Gleason 5), and metastatic prostate cancer. (B) Mean fluorescence intensity was compared between different tissues. *All images were reviewed by a pathologist.
Figure 2.
Figure 2.
Kaplan–Meier analyses were conducted for PFS after ADT vs. (A) Gleason score, and (B) local therapy. Kaplan–Meier analysis was also compared with (C) race for patients who had not reached PSA nadir. Similar analyses were conducted for PFS after PSA nadir vs. (D) Gleason score, (E) local therapy. Overall survival of patients with low vs. high Gleason score is also included (F).
See this image and copyright information in PMC

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