Diagnostic potential of SDHB mRNA contained in serum extracellular vesicles among patients with prostate cancer.

IF 2.6 3区医学 Q3 ENDOCRINOLOGY & METABOLISM Prostate Pub Date : 2024-12-01 Epub Date: 2024-09-15 DOI:10.1002/pros.24792

Taku Kato, Eiji Sugihara, Yuko Hata, Kyojiro Kawakami, Yasunori Fujita, Kosuke Mizutani, Tatsuya Ando, Yasuhiro Sakai, Kouhei Sakurai, Shohei Toyota, Hidetoshi Ehara, Masafumi Ito, Hiroyasu Ito

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引用次数: 0

Abstract

Background: Androgen receptor signaling inhibitors(ARSIs) have been used to treat patients with metastatic prostate cancer (PC) and castration-resistant prostate cancer (CRPC). In this study, we aimed to identify novel serum extracellular vesicle (EV)-based biomarkers to diagnose ARSI-resistance and therapeutic targets for ARSI-resistant CRPC.

Methods: Total RNA contained in serum EVs from 5 cases of CRPC before ARSI treatment and after acquiring ARSI-resistance was subjected to RNA-sequencing. The expression changes of selected RNAs contained in EVs were confirmed in 48 cases of benign prostatic hyperplasia (BPH) and 107 PC using reverse transcription-quantitative PCR (RT-qPCR) and compared with tissue RNA expression using public datasets.

Results: RNA-sequencing revealed that mitochondrial oxidative phosphorylation (OXPHOS)-related genes were increased in EVs after acquiring ARSI-resistance. Among them, RT-qPCR and datasets analysis demonstrated that SDHB mRNA was upregulated after acquiring ARSI-resistance in EVs and ARSI-exposed PC tissue compared to ARSI-naïve EVs and tissue, respectively. SDHB mRNA levels both in EVs and tissue were increased in localized PC compared with BPH and decreased in advanced PC. Tissue expression of SDHB mRNA was significantly correlated with those of other OXPHOS-related genes. SDHB mRNA in EVs (EV-SDHB) was elevated among 3 out of 7 ARSI-treating patients with stable PSA levels who later progressed to ARSI-resistant CRPC.

Conclusions: The levels of OXPHOS-related mRNAs in EVs correlated with those in PC tissue, among which SDHB mRNA was found to be a novel biomarker to diagnose ARSI-resistance. EV-SDHB may be useful for early diagnosis of ARSI-resistance.

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前列腺癌患者血清细胞外囊泡中所含 SDHB mRNA 的诊断潜力。

背景：雄激素受体信号抑制剂（ARSIs）已被用于治疗转移性前列腺癌（PC）和阉割耐药前列腺癌（CRPC）患者。在这项研究中，我们旨在鉴定基于血清胞外囊泡（EV）的新型生物标记物，以诊断ARSI耐药和ARSI耐药CRPC的治疗靶点：方法：对5例CRPC患者在ARSI治疗前和获得ARSI耐药后的血清EV所含的总RNA进行RNA测序。采用逆转录定量 PCR（RT-qPCR）技术确认了 48 例良性前列腺增生症（BPH）和 107 例 PC 中 EVs 中所含特定 RNA 的表达变化，并利用公开数据集将其与组织 RNA 表达进行了比较：结果：RNA测序发现，获得ARSI抗性后，EVs中线粒体氧化磷酸化（OXPHOS）相关基因增加。其中，RT-qPCR和数据集分析表明，与抗ARSI的EV和组织相比，抗ARSI的EV和暴露于ARSI的PC组织中的SDHB mRNA分别上调。与良性前列腺增生症相比，局部PC的EV和组织中的SDHB mRNA水平均升高，而晚期PC的SDHB mRNA水平则降低。组织中SDHB mRNA的表达与其他OXPHOS相关基因的表达明显相关。在7名PSA水平稳定的ARSI治疗患者中，有3名后来发展为ARSI耐药的CRPC，他们的EV中SDHB mRNA（EV-SDHB）升高：结论：EV中的OXPHOS相关mRNA水平与PC组织中的相关mRNA水平相关，其中SDHB mRNA是诊断ARSI耐药的新型生物标记物。EV-SDHB可能有助于早期诊断ARSI耐药性。

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

Prostate 医学-泌尿学与肾脏学

CiteScore

5.10

自引率

3.60%

发文量

180

审稿时长

1.5 months

期刊介绍： The Prostate is a peer-reviewed journal dedicated to original studies of this organ and the male accessory glands. It serves as an international medium for these studies, presenting comprehensive coverage of clinical, anatomic, embryologic, physiologic, endocrinologic, and biochemical studies.