Biological markers in breast carcinoma—clinical correlations with pseudouridine, n2,N2-dimethylguanosine, and 1-methylinosine

Abstract

Urinary levels of the minor nucleosides, pseudouridine (Ψ), N², N²-dimethylguanosine (m²₂G), and 1-methylinosine (m¹I), were investigated in patients with breast carcinoma. Elevated levels of Ψ were observed in 27/131 (20.6%) patients with metastatic disease, 1/14 (7.1%) preoperative patients, and 1/28 (3.6%) postoperative N+ patients. Elevated levels of m²₂G and M¹I were observed, respectively, in 46/131 (35.1%) and 27/131 (20.6%) patients with metastatic disease, 3/14 (21.4%), and 0/14 preoperative patients, and 6/28 (21.4%) and 2/28 (7.1%) postoperative N+ patients. There was no correlation between nucleoside levels and involvement of specific organ sites with metastatic disease, nor with chemotherapy response rate or time to treatment failure. During the treatment of metastatic disease there was a tendency for elevated pretherapy Ψ levels to decrease with attainment of a response and, if the levels subsequently rose, to be associated with treatment failure. However, increasing levels of m²₂G and m¹I occurred with both response and disease progression. These results suggest that routine measurement of the level of the urinary nucleosides would be of limited value for following the disease course in patients with breast cancer.