The prognostic impact of reduction of 5-hydroxymethyl-2'-deoxycytidine in non-tumoral tissue of upper tract urothelial carcinoma patients evaluated by mass spectrometry

Reduction of 5-hydroxymethyl-2'-deoxycytidine (5hmdC) is related to poor prognosis in malignant tumor patients. However, reports on its role in urological cancers, particularly upper tract urothelial carcinoma (UTUC), are still limited. This study evaluated the relationship between 5hmdC levels and oncological outcomes including overall survival (OS) and metastasis-free survival (MFS) in patients with non-metastatic UTUC. Tumoral and non-tumoral tissues were obtained from patients who underwent nephroureterectomy between March 2012 and December 2024. 5hmdC accumulation was assessed by immunohistochemistry (IHC), and quantified using molar ratio by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). Eighty-five and 82 paired samples were evaluated by IHC and LC-MS/MS, respectively. The significant reduction of 5hmdC accumulation in tumoral tissue compared with non-tumoral tissue was observed by both evaluations ( P  < 0.001 and P  < 0.001, respectively). In the investigation of prognostic impact, low molar ratio in non-tumoral tissue demonstrated significantly poor overall survival than the other (68.8 months vs. not reached, P  = 0.035) and inferior trend of MFS (not reached vs not reached, respectively, P  = 0.061). In conclusion, the reduction of 5hmdC in non-tumoral tissue may be associated with poor prognosis in patients with non-metastatic UTUC.