{"title":"前列腺癌患者血清细胞外囊泡中所含 SDHB mRNA 的诊断潜力。","authors":"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","doi":"10.1002/pros.24792","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>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.</p>","PeriodicalId":54544,"journal":{"name":"Prostate","volume":" ","pages":"1515-1524"},"PeriodicalIF":2.6000,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Diagnostic potential of SDHB mRNA contained in serum extracellular vesicles among patients with prostate cancer.\",\"authors\":\"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\",\"doi\":\"10.1002/pros.24792\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>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.</p>\",\"PeriodicalId\":54544,\"journal\":{\"name\":\"Prostate\",\"volume\":\" \",\"pages\":\"1515-1524\"},\"PeriodicalIF\":2.6000,\"publicationDate\":\"2024-12-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Prostate\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1002/pros.24792\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/9/15 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q3\",\"JCRName\":\"ENDOCRINOLOGY & METABOLISM\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Prostate","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1002/pros.24792","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/9/15 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"ENDOCRINOLOGY & METABOLISM","Score":null,"Total":0}
Diagnostic potential of SDHB mRNA contained in serum extracellular vesicles among patients with prostate cancer.
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.
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.
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