Abstract
Recent evidence indicates that small noncoding RNA molecules, known as microRNAs (miRNAs), are involved in cancer initiation and progression. We hypothesized that genetic variations in miRNAs and miRNA target sites could be associated with the efficacy of androgen-deprivation therapy (ADT) in men with prostate cancer. We systematically evaluated 61 common single nucleotide polymorphisms (SNPs) inside miRNAs and miRNA target sites in a cohort of 601 men with advanced prostate cancer treated with ADT. The prognostic significance of these SNPs on disease progression, prostate cancer-specific mortality (PCSM) and all-cause mortality (ACM) after ADT were assessed by Kaplan-Meier analysis and Cox regression model. Four, seven, and four SNPs were significantly associated with disease progression, PCSM, and ACM, respectively, after ADT in univariate analysis. KIF3C rs6728684, CDON rs3737336, and IFI30 rs1045747 genotypes remained as significant predictors for disease progression; KIF3C rs6728684, PALLD rs1071738, GABRA1 rs998754, and SYT9 rs4351800 remained as significant predictors for PCSM; and SYT9 rs4351800 remained as a significant predictor for ACM in multivariate models that included clinicopathologic predictors. Moreover, strong combined genotype effects on disease progression and PCSM were also observed. Patients with a greater number of unfavorable genotypes had a shorter time to progression and worse prostate cancer-specific survival during ADT (P for trend < 0.001). SNPs inside miRNAs and miRNA target sites have a potential value to improve outcome prediction in prostate cancer patients receiving ADT.
Highlights
With the advent of prostate-specific antigen (PSA) screening, prostate cancer is being detected and treated earlier
Our results suggest that a simple and pretreatment analysis for microRNA single nucleotide polymorphisms (SNPs) might add significant prognostic value to the currently used indicators for outcome prediction in patients receiving Androgen deprivation therapy (ADT)
The prostate cancer patients who had been treated with ADT, including those with disease recurrence after local treatments, were identified and followed up prospectively to evaluate genetic variants as prognostic predictors of clinical outcomes during ADT
Summary
With the advent of prostate-specific antigen (PSA) screening, prostate cancer is being detected and treated earlier. Approximately 10% to 20% of newly diagnosed prostate cancer patients present advanced disease, and many others will eventually relapse despite local treatments. A variety of prediction parameters, such as tumor stage, Gleason score, and PSA kinetics, have been used in clinical practice to define the presentation of prostate cancer and adapt the treatment strategy [4,5,6]. Their prognostic capabilities are still limited and might be improved by the incorporation of other factors including genetic markers.
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