Identification and verification of an ALYREF-involved 5-methylcytosine based signature for stratification of prostate cancer patients and prediction of clinical outcome and response to therapies
-
Published:2023-05-08
Issue:1
Volume:14
Page:
-
ISSN:2730-6011
-
Container-title:Discover Oncology
-
language:en
-
Short-container-title:Discov Onc
Author:
Tan Xiao,Cai Zhouda,Chen Guo,Cai Chao,Chen Jiahong,Liang Yingke,Zhuo Yangjia,Liu Jianming,Huang Liangliang,Ouyang Bin,Wei Yanni,Jia Zhenyu,Deng Junhong,Zhong Weide,Lu Jianming
Abstract
Abstract
Objectives
Due to the heterogeneity of PCa, the clinical indicators used for PCa can't satisfy risk prognostication and personalized treatment. It is imperative to develop novel biomarkers for prognosis prediction and therapy response in PCa. Accumulating evidence shows that non-mutational epigenetic reprogramming, independent from genomic instability and mutation, serves as a newly added hallmark in cancer progression.
Methods
In this study, we integrated multi-center cohorts (N > 1300) to develop a RNA 5-methylcytosine regulator-based signature, the m5C score. We performed unsupervised clustering and LASSO regression to identify novel m5C-related subtypes and calculate the m5C score. Then we assessed the role of m5C cluster and m5C score in several clinical aspects such as prognosis in various molecular subtypes, responses to chemotherapy, androgen receptor signaling inhibitor (ARSI) therapy and immunotherapy in PCa. Finally, we validated the cancer-promoting performance of ALYREF through clinical data analysis and experiments in vivo and in vitro.
Results
The investigation revealed that the m5C score could accurately predict the biochemical recurrence (BCR) in different subtypes (the PAM50 subtypes and immunophenotypes) and the responses to chemotherapy, ARSI therapy, and immunotherapy (PD1/PD-L1). A high m5C score indicated a poor BCR prognosis in every subtype of PCa, unfavorable responses in ARSI therapy and immunotherapy (PD1/PD-L1). Moreover, the m5C reader gene termed ALYREF, yielding the highest weighed coefficient, promoted PCa progression through in silico analysis and experimental validations (in vivo and in vitro).
Conclusions
The m5C signature can function in many aspects of PCa, such as the development and prognosis of the disease, and multiple therapy responses. Further, the m5C reader, ALYREF, was identified as a prognostic biomarker and a potential therapeutic target for PCa. The m5C signature could act as a brand-new tool for predicting the prognosis of patients in different molecular subtypes and patients’ therapy responses and promoting customized treatments.
Publisher
Springer Science and Business Media LLC
Subject
Cancer Research,Endocrine and Autonomic Systems,Endocrinology,Oncology,Endocrinology, Diabetes and Metabolism
Reference36 articles.
1. Culp MB, Soerjomataram I, Efstathiou JA, Bray F, Jemal A. Recent global patterns in prostate cancer incidence and mortality rates. Eur Urol. 2020;77(1):38–52. 2. Sandhu S, Moore CM, Chiong E, Beltran H, Bristow RG, Williams SG. Prostate cancer. Lancet (London, England). 2021. https://doi.org/10.1016/S0140-6736(21)00950-8. 3. Guo G, Pan K, Fang S, Ye L, Tong X, Wang Z, Xue X, Zhang H. Advances in mRNA 5-methylcytosine modifications: detection, effectors, biological functions, and clinical relevance. Mol Ther Nucleic Acids. 2021;26:575–93. 4. Dai E, Zhu Z, Wahed S, Qu Z, Storkus WJ, Guo ZS. Epigenetic modulation of antitumor immunity for improved cancer immunotherapy. Mol Cancer. 2021;20(1):171. 5. Chen X, Li A, Sun BF, Yang Y, Han YN, Yuan X, Chen RX, Wei WS, Liu Y, Gao CC, et al. 5-methylcytosine promotes pathogenesis of bladder cancer through stabilizing mRNAs. Nat Cell Biol. 2019;21(8):978–90.
Cited by
1 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献
|
|