Possibility of using mRNA expression levels for nucleic acid-metabolizing enzymes within prostate cancer cells as indices for prognostic factors

Abstract

Thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD), thymidine phosphorylase (TP) and orotate phosphoribosyl transferase (OPRT) are enzymes involved in nucleic acid metabolism. It has been reported (based on observations of various tumor types) that the extent of the mRNA expression of these enzymes within tumor tissues may be used as a factor to define tumor prognosis. It has also been reported that the mRNA expression patterns differ in each type of tumor. However, few reports are available on the distribution of mRNA expression in prostate cancers. This study was conducted on tissue specimens obtained from 172 patients who were diagnosed with prostate cancer and had undergone total prostatectomies. The mRNA expression of TS, DPD, OPRT and TP was quantitatively analyzed using the Danenberg tumor profile (DTP) method. The results were used to examine the correlations between the distributions of the mRNAs and clinicopathological factors, as well as the significance of their expression as a prognostic factor. Patients with poorly differentiated cancers in their tissues showed a significant increase in the mRNA expression of TS and OPRT. The increases in the TP mRNA content were proportional to an increase in the Gleason scores. The prognosis was significantly poorer in those cases with a high expression of TS or OPRT mRNA and a low expression of DPD mRNA. In conclusion, the expression levels of mRNAs for TS, DPD and OPRT among the enzymes related to nucleic acid metabolism are useful as prognostic factors in patients with prostate cancers.

Figure 1

PSA relapse-free survival according to mRNA expression level. Relationship between PSA relapse-free survival and mRNA expression of TS, DPD, TP and OPRT. mRNA were divided into two groups with a high and low expression.