Moderated Poster Session

MP69-04: Kynurenine pathway is strongly associated with clinicopathological features and response to neoadjuvant chemotherapy in patients with upper tract urothelial carcinoma

Poster Presenter(s)

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  Kenji Zennami, MD

  Fujita Medical University

Introduction: 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