LSD1+8a is an RNA biomarker of neuroendocrine prostate cancer

IF 4.8 2区医学 Q1 Biochemistry, Genetics and Molecular Biology

Neoplasia Pub Date : 2025-03-14 DOI:10.1016/j.neo.2025.101151

Anbarasu Kumaraswamy , Rahul Mannan , Olivia A. Swaim , Eva Rodansky , Xiao-Ming Wang , Aaron Udager , Rohit Mehra , Hui Li , Colm Morrissey , Eva Corey , Michael C. Haffner , Peter S. Nelson , Arul M. Chinnaiyan , Joel A. Yates , Joshi J. Alumkal

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引用次数: 0

Abstract

Background

Lysine-specific demethylase 1 (LSD1) is a histone demethylase and regulator of differentiation, including in cancer. A neuronal-specific isoform of LSD1—LSD1+8a—has been shown to play a key role in promoting neuronal differentiation in the developing brain. We previously determined that LSD1+8a transcripts were detected in an aggressive subtype of prostate cancer harboring a neuronal program—neuroendocrine prostate cancer (NEPC)—but not in prostate adenocarcinomas harboring a glandular program. However, the number of samples examined was limited.

Methods

Using a large collection of prostate cancer patient cell lines and patient-derived xenografts (PDXs), we measured LSD1+8a using quantitative polymerase chain reaction (qPCR), RNA in situ hybridization (RNA-ISH), and protein detection methods. We then validated our findings using an independent cohort of patient tumor samples.

Results

LSD1+8a mRNA expression was detected in every NEPC cell line and PDX examined by qPCR and RNA-ISH but in none of the prostate adenocarcinomas. We validated the RNA-ISH results in patient tumors, confirming that LSD1+8a was expressed in all NEPC tumors but in none of the adenocarcinomas. Finally, we generated a rabbit monoclonal antibody specific to LSD1+8a protein and confirmed its specificity using normal neuronal tissue samples. However, LSD1+8a protein was not detectable in NEPC tumors—likely due to the substantially lower levels of LSD1+8a mRNA in NEPC tumors vs. normal neuronal tissues.

Conclusions

Measuring LSD1+8a mRNA is a sensitive and specific method for the diagnosis of NEPC, which is often challenging.

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LSD1+8a 是神经内分泌性前列腺癌的 RNA 生物标记物

赖氨酸特异性去甲基酶1 （LSD1）是一种组蛋白去甲基酶和分化调节剂，包括在癌症中。LSD1-LSD1 +8a的神经元特异性亚型已被证明在促进发育中的大脑神经元分化中发挥关键作用。我们之前确定LSD1+8a转录本在一种具有神经元程序的侵袭性前列腺癌亚型——神经内分泌前列腺癌（NEPC）中检测到，但在具有腺程序的前列腺癌中未检测到。然而，检查的样本数量有限。方法采用定量聚合酶链式反应（qPCR）、RNA原位杂交（RNA- ish）和蛋白检测方法，对大量前列腺癌患者细胞系和患者来源的异种移植物（PDXs）进行LSD1+8a检测。然后，我们使用独立的患者肿瘤样本队列验证了我们的发现。结果slsd1 +8a mRNA在NEPC细胞系和PDX细胞系中均有表达，但在前列腺腺癌中均无表达。我们在患者肿瘤中验证了RNA-ISH结果，证实LSD1+8a在所有NEPC肿瘤中表达，但在腺癌中没有表达。最后，我们制备了一种针对LSD1+8a蛋白的兔单克隆抗体，并利用正常神经元组织样本证实了其特异性。然而，在NEPC肿瘤中未检测到LSD1+8a蛋白，这可能是由于NEPC肿瘤中LSD1+8a mRNA水平明显低于正常神经元组织。结论检测LSD1+8a mRNA是诊断NEPC的一种敏感、特异的方法，但往往具有挑战性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Neoplasia 医学-肿瘤学

CiteScore

9.20

自引率

2.10%

发文量

审稿时长

26 days

期刊介绍： Neoplasia publishes the results of novel investigations in all areas of oncology research. The title Neoplasia was chosen to convey the journal’s breadth, which encompasses the traditional disciplines of cancer research as well as emerging fields and interdisciplinary investigations. Neoplasia is interested in studies describing new molecular and genetic findings relating to the neoplastic phenotype and in laboratory and clinical studies demonstrating creative applications of advances in the basic sciences to risk assessment, prognostic indications, detection, diagnosis, and treatment. In addition to regular Research Reports, Neoplasia also publishes Reviews and Meeting Reports. Neoplasia is committed to ensuring a thorough, fair, and rapid review and publication schedule to further its mission of serving both the scientific and clinical communities by disseminating important data and ideas in cancer research.