@Article{or.2023.028321,
AUTHOR = {SHA ZHU, NANWEI XU, JIAYU LIANG, FENGNIAN ZHAO, ZILIN WANG, YUCHAO NI, JINDONG DAI, JINGE ZHAO, XINGMING ZHANG, JUNRU CHEN, GUANGXI SUN, PENGFEI SHEN, HAO ZENG},
TITLE = {Mutations in epigenetic regulator <i>KMT2C</i> detected by liquid biopsy are associated with worse survival in prostate cancer patients},
JOURNAL = {Oncology Research},
VOLUME = {31},
YEAR = {2023},
NUMBER = {4},
PAGES = {605--614},
URL = {http://www.techscience.com/or/v31n4/53316},
ISSN = {1555-3906},
ABSTRACT = { <b>Background:</b> KMT2 (lysine methyltransferase) family enzymes are epigenetic regulators that activate gene transcription. <i>KMT2C</i> is mainly involved in enhancer-associated H3K4me1, and is also one of the top mutated genes in cancer (6.6% in pan-cancer). Currently, the clinical significance of <i>KMT2C</i> mutations in prostate cancer is understudied. <b>Methods:</b> We included 221 prostate cancer patients diagnosed between 2014 and 2021 in West China Hospital of Sichuan University with cell-free DNA-based liquid biopsy test results in this study. We investigated the association between <i>KMT2C</i> mutations, other mutations, and pathways. Furthermore, we evaluated the prognostic value of <i>KMT2C</i> mutations, measured by overall survival (OS) and castration resistance-free survival (CRFS). Also, we explored the prognostic value of <i>KMT2C</i> mutations in different patient subgroups. Lastly, we investigated the predictive value of <i>KMT2C</i> mutations in individuals receiving conventional combined anti-androgen blockade (CAB) and abiraterone (ABI) as measured by PSA progression-free survival (PSA-PFS). <b>Results:</b> The <i>KMT2C</i> mutation rate in this cohort is 7.24% (16/221). <i>KMT2C</i>-mutated patients showed worse survival than <i>KMT2C</i>-wild type (WT) patients regarding both CRFS and OS (CRFS: mutated: 9.9 <i>vs</i>. WT: 22.0 months, <i>p</i> = 0.015; OS: mutated: 71.9 <i>vs</i>. WT 137.4 months, <i>p</i> = 0.012). <i>KMT2C</i> mutations were also an independent risk factor in OS [hazard ratio: 3.815 (1.461, 9.96), <i>p</i> = 0.006] in multivariate analyses. Additionally, we explored the association of <i>KMT2C</i> mutations with other genes. This showed that <i>KMT2C</i> mutations were associated with Serine/Threonine-Protein Kinase 11 (<i>STK11</i>, <i>p</i> = 0.004) and Catenin Beta 1 (<i>CTNNB1</i>, <i>p</i> = 0.008) mutations. In the CAB treatment, <i>KMT2C</i>-mutated patients had a significantly shorter PSA-PFS compared to <i>KMT2C</i>-WT patients. (PSA-PFS: mutated: 9.9 <i>vs</i>. WT: 17.6 months, <i>p</i> = 0.014). Moreover, <i>KMT2C</i> mutations could effectively predict shorter PSA-PFS in 10 out of 23 subgroups and exhibited a strong trend in the remaining subgroups. <b>Conclusions:</b> <i>KMT2C</i>-mutated patients showed worse survival compared to <i>KMT2C</i>-WT patients in terms of both CRFS and OS, and <i>KMT2C</i> mutations were associated with <i>STK11</i> and <i>CTNNB1</i> mutations. Furthermore, <i>KMT2C</i> mutations indicated rapid progression during CAB therapy and could serve as a potential biomarker to predict therapeutic response in prostate cancer.},
DOI = {10.32604/or.2023.028321}
}