Inherited Variants in Wnt Pathway Genes Influence Outcomes of Prostate Cancer Patients Receiving Androgen Deprivation Therapy

Abstract

Aberrant Wnt signaling has been associated with many types of cancer. However, the association of inherited Wnt pathway variants with clinical outcomes in prostate cancer patients receiving androgen deprivation therapy (ADT) has not been determined. Here, we comprehensively studied the contribution of common single nucleotide polymorphisms (SNPs) in Wnt pathway genes to the clinical outcomes of 465 advanced prostate cancer patients treated with ADT. Two SNPs, adenomatous polyposis coli (APC) rs2707765 and rs497844, were significantly (p ≤ 0.009 and q ≤ 0.043) associated with both prostate cancer progression and all-cause mortality, even after multivariate analyses and multiple testing correction. Patients with a greater number of favorable alleles had a longer time to disease progression and better overall survival during ADT (p for trend ≤ 0.003). Additional, cDNA array and in silico analyses of prostate cancer tissue suggested that rs2707765 affects APC expression, which in turn is correlated with tumor aggressiveness and patient prognosis. This study identifies the influence of inherited variants in the Wnt pathway on the efficacy of ADT and highlights a preclinical rationale for using APC as a prognostic marker in advanced prostate cancer.

WNT signalling in prostate cancer

“…In addition, analysis of single nucleotide polymorphisms (SNPs) in WNT pathway genes identified links between gene variants of APC and reduced PSA-free survival 73 and prostate cancer progression 74 .…”

Advances in Biomarkers for PCa Diagnostics and Prognostics—A Way towards Personalized Medicine

“…To conclude, the identification of clinically significant PCa by biomarkers and image modalities (mpMRI) is a step towards personalized diagnosis, which will be the future. Also for advanced PCa, results of this Special issue [ 24 ] might influence personalized PCa management.…”

“…Five studies present their basic research data using PCa cell lines [ 14 , 15 , 16 , 17 ] or summarize data on cancer/testis antigens (CTAs) as potential PCa biomarkers [ 18 ]. Serum markers are the subject in the vast majority of publications ( n = 8) with focus on PCa diagnostic and prognostic [ 19 , 20 , 21 , 22 , 23 ] or evaluation of advanced/metastatic disease stages [ 24 , 25 , 26 ]. Two of the four reviews further summarize biomarkers for PCa diagnostic [ 27 ] or active surveillance [ 28 ] while the other two reviews have special topics like nanoparticles as theranostic vehicles [ 29 ] or PCa stem cells [ 30 ].…”

“…Geng et al [ 24 ] checked first whether genetic variants in the Wnt pathway influence clinical outcomes for advanced PCa patients receiving androgen deprivation therapy (ADT). In 465 PCa patients, two common single nucleotide polymorphisms (SNPs), the adenomatous polyposis coli (APC) rs2707765 and rs497844, were significantly associated with both PCa progression and all-cause mortality [ 24 ]. This may implement a preclinical rationale for using APC as a prognostic marker in advanced PCa by identifying patients who would not benefit from ADT [ 24 ].…”

Clinical characteristics and ABCC2 genotype in Dubin-Johnson syndrome: A case report and review of the literature

“…During laparoscopy, DJS cases display a pathognomonic "black liver", which results from excessive deposition of a melanin-like pigment in the lysosomes of hepatocytes[ 2 , 3 ]. Surprisingly, few diagnostic tools are available to detect this syndrome during liver function and physical examinations[ 4 - 7 ]. Additionally, some DJS cases share symptoms, such as dull pain in the liver area, generalized weakness, fatigue, and loss of appetite, with other diseases, which inevitably leads to misdiagnosis[ 8 ].…”