Outcome measures were disease-free survival and tissue markers [thymidine phosphorylase (TP), dihydropyrimidine dehydrogenase (DPD) protein levels and TP, DPD, thymidylate synthase (TS) and orotate phosphoribosyltransferase (OPRT) mRNA levels in tumor samples and TS tandem-repeat type in blood samples].
No significant correlation was observed between the mRNA expression and location of the tumor, histopathologic type, clinical stage, and other clinicopathologic variables, with the exception that OPRT mRNA had a weak correlation with drug sensitivity against 5FU (R=0.219, p=0.0343).
Among HCCs, 15 of the 19 cases were negative forOPRT in the central area of the tumor, but 8 of the 19 cases expressed OPRT in vascularly invasive lesions.
In univariate analyses, low TS, high OPRT and low TP were significantly associated with a tumor shrinkage and a long survival, whereas DPD and UP gene expressions did not correlate with response and survival.
Orotate phosphoribosyltransferase (OPRT) is a key enzyme in the anabolism of 5-fluorouracil (5-FU), and its expression in tumors is thought to increase the efficacy of 5-FU against the tumor.