You have accessJournal of UrologyCME1 Apr 2023MP69-04 KYNURENINE PATHWAY IS STRONGLY ASSOCIATED WITH CLINICOPATHOLOGICAL FEATURES AND RESPONSE TO NEOADJUVANT CHEMOTHERAPY IN PATIENTS WITH UPPER TRACT UROTHELIAL CARCINOMA Kenji Zennami, Makoto Sumitomo, Takuhisa Nukaya, Masashi Takenaka, Manabu Ichino, Kiyoshi Takahara, Hitomi Sasaki, Maeda Yasuhiro, and Ryoichi Shiroki Kenji ZennamiKenji Zennami More articles by this author , Makoto SumitomoMakoto Sumitomo More articles by this author , Takuhisa NukayaTakuhisa Nukaya More articles by this author , Masashi TakenakaMasashi Takenaka More articles by this author , Manabu IchinoManabu Ichino More articles by this author , Kiyoshi TakaharaKiyoshi Takahara More articles by this author , Hitomi SasakiHitomi Sasaki More articles by this author , Maeda YasuhiroMaeda Yasuhiro More articles by this author , and Ryoichi ShirokiRyoichi Shiroki More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003332.04AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Metabolomics offers a potential role for discovering biomarkers and therapeutic targets by comprehensive screening of metabolites from patients with various cancers. However, metabolomic analysis using upper tract urothelial carcinoma (UTUC) tissue has not been reported. Therefore, we aimed to identify metabolites associated with clinicopathological features and response to neoadjuvant chemotherapy (NAC) in patients with UTUC. METHODS: Patients receiving treatment following a clinical diagnosis of UTUC at the Fujita Health University between October 2019 and August 2022 were enrolled in this study. We assessed 47 consecutive patients for whom a tumor tissue sample and nontumor tissue sample. Concentrations of metabolites were determined by high-performance liquid chromatography–tandem mass spectrometry (HPLC-MS/MS). For the analysis of the associations of kynurenine (Kyn) /tryptophan (Trp) metabolism with the patients’ clinicopathological characteristics and response to NAC, the Kyn/Trp ratio (KTR) in tissue samples and the tumor/nontumor (T/N) ratio of Kyn and Trp were determined. RESULTS: We first screened tissue concentrations of 58 metabolites and found that Kyn was the key metabolite. Mann-Whitney U tests revealed significant differences in the tissue Kyn T/N ratio and KTR T/N ratio with pathological stage (p=0.03 and p=0.03; Figure 1A and 1B). The tissue Kyn T/N ratio and KTR T/N ratio were also associated with tumor grade (p=0.02 and p=0.01; Figure 1C and 1D). KTR T/N ratio showed significant association with the presence of lymphovascular invasion (LVI) (p=0.01; Figure 1F), while Kyn T/N ratio was not statistically significant although there was a similar tendency (p=0.08; Figure 1E). In addition, the tissue Kyn T/N ratio and KTR T/N ratio were significantly associated with pathological downstaging (pDS) (p=0.003 and p=0.01; Figure 1G and 1H). CONCLUSIONS: Our study found that Try-Kyn pathway has a key role in the clinicopathological features of UTUC including stage, grade, and LVI. Since Kyn and KTR were associated with pDS, evaluation of Try-Kyn pathway using biopsy sample could be a predictive biomarker in NAC sensitivity, as well as appropriate adjuvant immune checkpoint inhibitors (ICIs) in NAC resistant case. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e964 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Kenji Zennami More articles by this author Makoto Sumitomo More articles by this author Takuhisa Nukaya More articles by this author Masashi Takenaka More articles by this author Manabu Ichino More articles by this author Kiyoshi Takahara More articles by this author Hitomi Sasaki More articles by this author Maeda Yasuhiro More articles by this author Ryoichi Shiroki More articles by this author Expand All Advertisement PDF downloadLoading ...