YB-1 Variant and Androgen Receptor Axis-Targeted Agents in Metastatic Castration-Resistant Prostate Cancer Patients

Abstract

Aim: To evaluate the influence of YB-1 rs10493112 variant as a genetic marker for response to second-generation androgen receptor axis-target agents. Methods: A hospital-based cohort study of 78 patients with metastatic castration-resistant prostate cancer was conducted. Genotyping was performed by TaqMan^® allelic discrimination technology. Main results: In abiraterone-treated and high-risk patients, YB-1 rs10493112 AA genotype carriers showed lower progression-free survival than C allele genotype patients (4 vs 17 months; p = 0.009). For carriers of AA genotype, multivariate Cox regression analysis revealed a fivefold increased risk of progression (p = 0.035). Conclusion: The study findings suggest that, for metastatic and castration-resistant prostate cancer patients, this polymorphism might be a putative marker for the clinical outcome.

Keywords::

• abiraterone acetate
• enzalutamide
• polymorphism
• prognosis
• prostate cancer
• second-generation androgen receptor axis-targeted agents
• YB-1

Author contributions

A Afonso and J Silva designed and performed experiments, analysed data and co-wrote the paper. AR Lopes, Sa Coelho, AS Patrão, A Rosinha, F Carneiro and MJ Maurício performed the recruitment of the patients. AR Pinto performed experiments. R Medeiros supervised the research, designed and performed experiments, analysed data and co-wrote the paper.

Financial & competing interests disclosure

This study was funded by the Liga Portuguesa Contra o Cancro-Centro Regional do Norte (Portuguese League Against Cancer), IPO-Porto (no. CI-IPOP-22-2015) and FCT-Fundação para a Ciência e Tecnologia. J Silva is a post-doctoral grant holder from Projecto Estratégico UID/DTP/00776/POCI-01-0145-FEDER-006868, funded by FCT/MCTES through national funds (PIDDAC) and co-funded by Fundo Europeu de Desenvolvimento Regional (FEDER) through Programa Operacional Competitividade e Internacionalização (POCI) (no. CI-IPOP-BPD2018-UID-DTP-00776-POCI-01-0145-FEDER-006868-GOMPV). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The study was approved by local review boards and performed according to the international regulations in Good Clinical Practices and to the ethical principles of the Declaration of Helsinki. All patients provided written informed consent prior to enrollment.

Additional information

Funding

This study was funded by the Liga Portuguesa Contra o Cancro-Centro Regional do Norte (Portuguese League Against Cancer), IPO-Porto (no. CI-IPOP-22-2015) and FCT-Fundação para a Ciência e Tecnologia. J Silva is a post-doctoral grant holder from Projecto Estratégico UID/DTP/00776/POCI-01-0145-FEDER-006868, funded by FCT/MCTES through national funds (PIDDAC) and co-funded by Fundo Europeu de Desenvolvimento Regional (FEDER) through Programa Operacional Competitividade e Internacionalização (POCI) (no. CI-IPOP-BPD2018-UID-DTP-00776-POCI-01-0145-FEDER-006868-GOMPV). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.