The urinary excretion of modified nucleosides has been found to be increased in a variety of neoplastic diseases and their measurement in urine provides an accurate indicator of the metabolism of RNA, especially transfer RNA. Altered patterns of excretion of these compounds might offer a sensitive biomarker for diagnosis and treat-ment of cancer. By means of a sensitive and specific method utilizing reversed-HPLC,, the excretion levels for urinary ribonucleosides were determined in random urine specimens from 95 patients with solid tumor malignancies. When compared to nor-mal control values, elevated levels of one or more of these compounds were found for patients in each of several tumor types studied. Patients with trophoblastic diseases (TRD) including partial mole, complete mole, invasive mole and choriocarcinoma had signi´ ficantly higher concentrations of pseudouridine, m7G, m1I, m1G and in2G Among these elevated nucleosides, positive rates of the pseudouridine as a´ marker for these TRD were over 88% except partial mole. Eighteen out of 35 patients with TRD was followed with serial nucleoside determination after treatment. Pseudouridine content was decreas-ed rapidly to normal value after surgery and effective chemotherapy. Excretion level of m5C which was not changed in other gynecologic cancer studied, was significant-ly increased in patients with serous cystadenocarcinoma, mucinous cystadenocar-cinoma and germ cell tumor of ovary. Contents of pseudouridine, m5C, m1I and m´G were increased significantly in urine of patients with hepatocellular carcinoma providing positive rates above 78% (positive rates for excretions of m5C and m´I were 100%).
In patients with stomach cancer, positive rates for those of pseudouridine, m5C and m2G were above 50%. The results suggest that pseudouridine level in urine is useful as a diagnostic marker for early detection of TRD and for monitoring the effectiveness of therapy. Also it is suggested that urinary levels of m5C for ovarian cancer, m5C and m1I for hepatocellular carcinoma and pseudouridine and m5C for stomach cancer respectively are useful as tumor markers.
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