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.

[A Renal Leiomyoma --A Case Report-].

A 49-year-old female was incidentally found to have a left renal tumor during a medical check-up. The tumor was too small to be fully diagnosed using computed tomography (CT) or magnetic resonance imaging (MRI). Since it was small and showed a homogenous enhancement pattern on contrast-enhanced CT, which made it difficult for us to distinguish the malignancy of the tumor, we performed regular CT follow-up. On the fifth year of her regular follow-up, the tumor had grown apparently larger and showed a heterogenous enhancement pattern, which suggested a malignant tumor. Since the tumor was exophytic, we decided to perform a laparoscopic partial nephrectomy. The operation was performed without any serious complications, and her renal function remained unchanged. The histopathology of the tumor was leiomyoma. Here, we discuss the characteristics of this tumor and the role of immunohistopathology in the diagnosis.

H19 in Serum Extracellular Vesicles Reflects Resistance to AR Axis-targeted Therapy Among CRPC Patients.

BACKGROUND/AIM: We aimed to evaluate the changes of androgen receptor (AR) signaling-related long non-coding RNAs (lncRNAs) in serum extracellular vesicles (EVs) from prostate cancer (PC) patients, in order to identify novel biomarkers for AR axis-targeted therapy (ARAT)-resistance among castration-resistant PC (CRPC) patients. PATIENTS AND METHODS: EVs were isolated from 2 patients before and after acquiring ARAT-resistance. RNA profiling of EVs was performed by RNA-sequencing. The expression levels of selected lncRNAs in EVs were analyzed by digital droplet PCR (ddPCR) in 58 localized and 14 metastatic PC patients at diagnosis, 7 ARAT-naïve and 6 ARAT-resistant CRPC patients. LncRNA H19 expression in PC tissue was examined using published data. In order to analyze the role of H19, the prognosis was analyzed in PC patients and proteomic analysis was performed in 22Rv1 PC cells. RESULTS: RNA-sequencing revealed that AR-regulated RNAs were most enriched in EVs after acquiring ARAT-resistance. Among them, up-regulation of AR signaling-related lncRNAs (PCAT1, H19, HOXA-11AS, ZEB1-AS1, ARLNC1, PART1, CTBP1-AS and PCA3) was confirmed by ddPCR. H19 contained in EVs (EV-H19) was significantly increased among ARAT-resistant patients compared to ARAT-naïve CRPC or metastatic PC patients. In PC tissue, H19 was negatively correlated with AR protein and AR-activity score and up-regulated in neuroendocrine CRPC tissue with low AR expression. Furthermore, EV-H19 expression was significantly associated with worse outcome to androgen-deprivation therapy. Proteomic analysis demonstrated that H19 knockdown enhanced PC-related protein expression. CONCLUSION: EV-H19 may negatively correlate with AR-signaling activity and could be a marker to diagnose ARAT-resistance among CRPC patients.

[A Case of Metastasis of Gastric Cancer to the Bladder].

A 62-year-old woman was diagnosed with peritoneal dissemination of gastric cancer and was treated with anticancer drugs. Eleven months after the start of the treatment, follow-up computed tomography newly showed thickening of the bladder wall and left hydronephrosis even though the chemotherapy reduced peritoneal dissemination. Therefore, she was referred to our hospital for further evaluation. Cystoscopy and magnetic resonance imaging showed the tumor arising from the bladder neck to trigone. A few days later, she was admitted to our hospital because of bladder tamponade. Transurethral coagulation was carried out, and we resected part of the bladder tumor for pathological examination at the same time. As the pathological features of the bladder tumor were similar to those of the primary stomach cancer and peritoneal dissemination, the diagnosis of the bladder tumor was metastatic gastric adenocarcinoma. She died three months after visiting our hospital.

Metastatic epithelioid angiomyolipoma treated with everolimus in a patient receiving hemodialysis: A case report.

INTRODUCTION: A patient undergoing hemodialysis and being treated with everolimus for metastatic epithelioid angiomyolipoma has never been described in the literature, to our knowledge. CASE PRESENTATION: A 53-year-old woman who had undergone trans-arterial embolization for epithelioid angiomyolipoma was referred with a chief complaint about right knee pain. Hemodialysis had been started after the embolization. Needle biopsy specimens of tumors obtained from behind the right kidney and in the right femur were diagnosed as epithelioid angiomyolipoma metastases. The patient underwent treatment with everolimus and achieved a partial response after 6 months of treatment without serious adverse events. CONCLUSION: Everolimus might be effective for patients with metastatic epithelioid angiomyolipoma who are undergoing hemodialysis.