دورية أكاديمية
Evaluating the Urinary Exosome microRNA Profile of von Hippel Lindau Syndrome Patients with Clear Cell Renal Cell Carcinoma.
العنوان: | Evaluating the Urinary Exosome microRNA Profile of von Hippel Lindau Syndrome Patients with Clear Cell Renal Cell Carcinoma. |
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المؤلفون: | Walter-Rodriguez B; Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA., Ricketts CJ; Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA., Linehan WM; Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA., Merino MJ; Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. |
المصدر: | Genes [Genes (Basel)] 2024 Jul 11; Vol. 15 (7). Date of Electronic Publication: 2024 Jul 11. |
نوع المنشور: | Journal Article |
اللغة: | English |
بيانات الدورية: | Publisher: MDPI Country of Publication: Switzerland NLM ID: 101551097 Publication Model: Electronic Cited Medium: Internet ISSN: 2073-4425 (Electronic) Linking ISSN: 20734425 NLM ISO Abbreviation: Genes (Basel) Subsets: MEDLINE |
أسماء مطبوعة: | Original Publication: Basel : MDPI |
مواضيع طبية MeSH: | Carcinoma, Renal Cell*/genetics , Carcinoma, Renal Cell*/urine , Exosomes*/genetics , Exosomes*/metabolism , von Hippel-Lindau Disease*/genetics , von Hippel-Lindau Disease*/urine , von Hippel-Lindau Disease*/complications , MicroRNAs*/urine , MicroRNAs*/genetics , Kidney Neoplasms*/genetics , Kidney Neoplasms*/urine , Biomarkers, Tumor*/urine , Biomarkers, Tumor*/genetics, Humans ; Female ; Male ; Middle Aged ; Adult ; Gene Expression Regulation, Neoplastic ; Aged |
مستخلص: | Introduction: Renal cell carcinoma is one of the ten more common malignant tumors worldwide, with a high incidence and mortality rate. Kidney cancer frequently presents at an advanced stage, and it is almost invariably fatal. Much progress has been made in identifying molecular targets for therapy in the hope of improving survival rates, but still, we have no good markers for early detection or progression of the disease. Von Hippel Lindau syndrome (VHL) is an autosomal dominant cancer hereditary syndrome in which affected individuals are at risk of developing bilateral and multifocal renal cell carcinomas (RCC) as well as other tumors. These patients provide an ideal platform to investigate the potential of urinary exosomal miRNA biomarkers in the early development of ccRCC, as these patients are regularly imaged and tumors are actively monitored until the tumor reaches 3 cm before surgical excision. This allows for pre- and post-surgical urine collection and comparison to excised tumor tissues. Studying different biomarkers in urine can provide comprehensive molecular profiling available to patients and physicians and can be a great source of additional tumor genetic information. Methods: Pre- and postoperative urine samples were obtained from a cohort of VHL patients undergoing surveillance and surgical excision of ccRCCs, and exosomes were extracted. MicroRNA-Seq analysis was performed on miRNA extracted from both urine-derived exosomes and FFPE material from excised ccRCCs. Results: MicroRNA-Seq analysis highlighted a significant difference in the urinary exosome-derived miRNA expression profiles between VHL patients and normal control individuals. This included decreased expression of the miR-320 family, such as miR-320a, known to be decreased in sporadic ccRCC and suppressed by the HIF1α transcription factor activated by the loss of the VHL gene. MiR-542-5p represented a potential marker of VHL-associated ccRCC that was lowly expressed in normal control urinary exosomes, significantly increased in the preoperative urinary exosomes of tumor-bearing VHL patients, and subsequently reduced to normal levels of expression after tumor excision. In concordance with this, the expression of miR-542-5p was increased in the VHL-associated ccRCC in comparison to the normal kidney. Conclusions: This study shows the potential for miRNA profiling of exosomes from readily available biofluids to both distinguish VHL patient urine from normal control urine microRNAs and to provide biomarkers for the presence of VHL syndrome-associated ccRCC. Further validation studies are necessary to demonstrate the utility of urinary exosome-derived miRNAs as biomarkers in kidney cancer. |
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فهرسة مساهمة: | Keywords: VHL; ccRCC; liquid biopsy; miRNA; molecular markers; renal cell carcinoma; urinary exosomes; von Hippel Lindau |
المشرفين على المادة: | 0 (MicroRNAs) 0 (Biomarkers, Tumor) |
تواريخ الأحداث: | Date Created: 20240727 Date Completed: 20240727 Latest Revision: 20240729 |
رمز التحديث: | 20240729 |
مُعرف محوري في PubMed: | PMC11276299 |
DOI: | 10.3390/genes15070905 |
PMID: | 39062684 |
قاعدة البيانات: | MEDLINE |
تدمد: | 2073-4425 |
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DOI: | 10.3390/genes15070905 |