MP17-20 EPIGENETIC REGULATOR KMT2C MUTATION DETECTED BY LIQUID BIOPSY IS ASSOCIATED WITH WORSE SURVIVAL IN PROSTATE CANCER PATIENTS

Abstract

You have accessJournal of UrologyCME1 Apr 2023MP17-20 EPIGENETIC REGULATOR KMT2C MUTATION DETECTED BY LIQUID BIOPSY IS ASSOCIATED WITH WORSE SURVIVAL IN PROSTATE CANCER PATIENTS Sha Zhu, Nanwei Xu, Fengnian Zhao, Zilin Wang, Yuchao Ni, Jindong Dai, Jinge Zhao, Jiayu Liang, Xingming Zhang, Junru Chen, Pengfei Shen, and Hao Zeng Sha ZhuSha Zhu More articles by this author , Nanwei XuNanwei Xu More articles by this author , Fengnian ZhaoFengnian Zhao More articles by this author , Zilin WangZilin Wang More articles by this author , Yuchao NiYuchao Ni More articles by this author , Jindong DaiJindong Dai More articles by this author , Jinge ZhaoJinge Zhao More articles by this author , Jiayu LiangJiayu Liang More articles by this author , Xingming ZhangXingming Zhang More articles by this author , Junru ChenJunru Chen More articles by this author , Pengfei ShenPengfei Shen More articles by this author , and Hao ZengHao Zeng More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003237.20AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: KMT2 (lysine methyltransferase) family enzymes exert epigenetic regulation to active gene transcription. KMT2C are mainly involved in enhancer-associated H3K4me1, and is also the top mutated genes in cancer (6.6% in pan-cancer). Currently, the clinical significance of KMT2C mutations in prostate cancer is understudied. METHODS: We included 221 prostate cancer patients diagnosed between 2014 and 2021 in West China Hospital of Sichuan University with cfDNA-based liquid biopsy test results in this study. We explored the association of KMT2C mutations with other mutations and investigates the prognostic significance of KMT2C mutation measured by overall survival (OS) and castration-resistance free survival (CFS). In addition, we explored the prognostic value of KMT2C mutation in different patient subgroups. RESULTS: The KMT2C mutation rate in this cohort is 7.24% (16/221). KMT2C-mutated patients showed worse survival compared to KMT2C-WT patients in terms of both CFS and OS (CFS: mutated: 9.9 vs. WT: 22.0 months, p=0.015; OS: mutated: 71.9 vs. WT 137.4 months, p=0.012). KMT2C mutation was also an independent risk factor in OS [HR: 3.815 (1.461, 9.96), p=0.006] in multivariate analyses. Besides, we also explored the association of KMT2C mutations and other genes, and the results showed that KMT2C mutation was related to Serine/Threonine-Protein Kinase 11 (STK11, p=0.004) and Catenin Beta 1 (CTNNB1, p=0.008) mutations. For OS, KMT2C mutation was significantly associated with survival in patient subgroups with PI3K pathway mutation (HR: 6.64, p=0.009) or WNT pathway mutation (HR: 2.44, p=0.043). CONCLUSIONS: KMT2C-mutated patients showed worse survival compared to KMT2C-WT patients in terms of both CFS and OS, and KMT2C mutation was associated with STK11 and CTNNB1 mutations. Furthermore, KMT2C mutation was significantly associated with survival in certain patient subgroups, such as patients with PI3K and WNT pathway mutation, etc. Source of Funding: The Natural Science Foundation of China (NSFC 81902577); The Research Foundation for the Postdoctoral Program of Sichuan University (2021SCU12014) © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e221 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Sha Zhu More articles by this author Nanwei Xu More articles by this author Fengnian Zhao More articles by this author Zilin Wang More articles by this author Yuchao Ni More articles by this author Jindong Dai More articles by this author Jinge Zhao More articles by this author Jiayu Liang More articles by this author Xingming Zhang More articles by this author Junru Chen More articles by this author Pengfei Shen More articles by this author Hao Zeng More articles by this author Expand All Advertisement PDF downloadLoading ...