Introduction:
COMT expression was reported to be associated with the recurrence of prostate cancer. Furthermore, it has been shown that rs165599 SNP in the 3’UTR of COMT affects the interaction between miR-138 and COMT, while another polymorphism (rs4680) located in the gene of COMT also affects its expression. Here, we explored the combined effect of rs165599 and rs4680 .

Material and methods:
Kaplan-Meier analysis was performed to analyze the PSA-progression-free survival of prostate cancer patients carrying different genotypes of rs165599 and rs4680 SNPs. IHC and Western blot were used to evaluate the expression of COMT. Real-time PCR was carried out to examine the expression of miR-138 and COMT mRNA. Luciferase assay was performed to explore the inhibitory role of miR-138 in the expression of COMT carrying different genotypes.

Results:
The PSA-progression-free survival was significantly increased in prostate cancer patients carrying the rs165599-AA + rs4680-Val/Val genotype. In concordance with this, the expression of COMT was remarkably elevated in the tissue samples collected from prostate cancer patients carrying the rs165599-AA + rs4680-Val/Val genotype. Luciferase assay demonstrated that COMT-G at rs165599 was effectively suppressed by miR-138 through binding to the 3’ UTR of COMT-G. Furthermore, COMT expression was notably suppressed by miR-138 precursors in primary prostate cancer cells carrying GG genotype at rs165599.

Conclusions:
The findings of this study demonstrated that the carriers of AA genotype of rs165599 and Val/Val genotype of rs4680 showed an increased risk of prostate cancer recurrence, and these two polymorphisms may jointly function as a novel biomarker for the prognosis of prostate cancer recurrence.