You have accessJournal of UrologyKidney Cancer: Basic Research & Pathophysiology I (MP39)1 Sep 2021MP39-01 SYSTEM ASC TRANSPORTER 2, A KEY ENZYME FOR GLUTAMINE PATHWAY, IS A POSSIBLE BIOMARKER FOR METASTATIC PROGRESSION AND SURVIVAL IN RENAL CELL CARCINOMA Yoshinari Muto, Makoto Sumitomo, Kenji Zennami, Masashi Takenaka, Takuhisa Nukaya, Kosuke Fukaya, Manabu Ichino, Kiyoshi Takahara, Hitomi Sasaki, and Ryoichi Shiroki Yoshinari MutoYoshinari Muto More articles by this author , Makoto SumitomoMakoto Sumitomo More articles by this author , Kenji ZennamiKenji Zennami More articles by this author , Masashi TakenakaMasashi Takenaka More articles by this author , Takuhisa NukayaTakuhisa Nukaya More articles by this author , Kosuke FukayaKosuke Fukaya 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 , and Ryoichi ShirokiRyoichi Shiroki More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002054.01AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: The glutamine (Gln) pathway has been implicated in tumor progression in various malignancies including renal cell carcinoma (RCC). However, the detail underlying this pathway remains to be elucidated. Since both glutaminase 1 (GLS1) and system ASC transporter 2 (ASCT2) were reported to play a crucial role in this pathway, we investigated whether these enzymes could be associated with cancer development and survival in RCC. METHODS: Tumor (T) and non-tumor (N) tissues were sampled from 66 RCC patients. Metabolome analyses were performed by liquid chromatography mass spectrometry (LC/MS) and important metabolites including Gln and glutamate (Glu) were analyzed. The protein expression of GLS1 and ASCT2 was evaluated by immunohistochemistry (IHC) using formalin-fixed, paraffin-embedded sections of surgical specimen from 80 metastatic RCC (mRCC) patients who received standard treatment using tyrosine-kinase inhibitors (TKIs) with or without immune checkpoint inhibitors (ICIs). The mRCC patients who received treatment with ICIs in the first- or second-line treatment were categorized into the “ICI group”, whereas others were categorized into the “TKI-only group”. In this study, the endpoint was progression-free survival 2 (PFS2) defined as the interval between first-line treatment and the second relapse. RESULTS: LC/MS analyses showed that both Gln T/N ratio and Glu T/N ratio in mRCC patients were significantly increased compared with those in non-mRCC patients (p=0.002 and p=0.048, respectively). On the other hand, the median value of Gln T/N ratios was shown to be over 100-fold higher than that of Glu T/N ratios. IHC analyses using mRCC tumor tissues revealed that ASCT2 was expressed more strongly in tumor cells than in normal cells, while GLS1 was expressed both in normal and tumor cells at the equal level. Kaplan–Meier analysis showed that ICI group had better PFS2 than TKI-only group in patients with ASCT2 high expression levels (p=0.009), while there was no significant difference on PFS2 between two groups in patients with ASCT2 low expression levels. CONCLUSIONS: Our results suggest that ASCT2 rather than GLS1 may be a key enzyme for Gln pathway in RCC. Our results also suggest that ASCT2 is associated with metastatic progression and survival, confirming its role as a possible biomarker to determine the appropriate treatment for mRCC patients. Source of Funding: None © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e704-e704 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Yoshinari Muto More articles by this author Makoto Sumitomo More articles by this author Kenji Zennami More articles by this author Masashi Takenaka More articles by this author Takuhisa Nukaya More articles by this author Kosuke Fukaya 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 Ryoichi Shiroki More articles by this author Expand All Advertisement Loading ...
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