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Combination of tumor suppressor miR-20b-5p,miR-30a-5p,and miR-196a-5p as a serum diagnostic panel for renal cell carcinoma
Institution:1. Guangdong and Shenzhen Key Laboratory of Male Reproductive Medicine and Genetics, Peking University Shenzhen Hospital, Shenzhen, Guangdong, 518036, China;2. Shantou University Medical College, Shantou, Guangdong, 515041, China;3. Anhui Medical University, Hefei, Anhui, 230032, China;4. Department of Urology, Shandong Provincial Hospital, Jinan, Shandong, 250021, China;1. Department and Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People''s Republic of China;2. School of Health Sciences, Macao Polytechnic Institute, Macao, People''s Republic of China;3. Department of Cell Death and Cancer Genetics, The Hormel Institute, University of Minnesota, Austin, Minnesota;4. The Wistar Institute, Philadelphia, Pennsylvania;1. Department of Pathology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310016, PR China;2. Department of Radiology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310016, PR China;3. Departmentof Gastroenterology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310016, PR China;4. Department of Pathology, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310016, PR China;1. Department of Pathology, Northwestern University Feinberg School of Medicine, 303 E Chicago Ave, Chicago, IL, 60611, USA;2. Division of Thoracic Surgery, Northwestern University Feinberg School of Medicine, 676 N St Clair St, Chicago, IL, 60611, USA;1. Laboratory of Molecular Pathology, State University of Londrina, Brazil;2. Laboratory of Pathophysiology and Free Radicals, State University of Londrina, Brazil;3. ZIK Plasmatis, Leibniz Institute for Plasma Science and Technology (INP), Greifswald, Germany;4. Department of Pathology and Legal Medicine, University of São Paulo, Brazil;5. Laboratory of Tissue Microenvironment, Federal University of Minas Gerais, Brazil;1. Department of Sense Organs, Sapienza University of Rome, Viale del Policlinico,155, Rome 00151, Italy;2. Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Corso della Repubblica 79, Latina 04100, Italy;3. Department of Internal Medicine and Medical Specialties, Rheumatology Unit, Sapienza University of Rome, Viale del Policlinico,155, Rome 00151, Italy;4. Department of Radiological, Oncological and Anatomic Pathology Sciences, Sapienza University of Rome, Viale del Policlinico,155, Rome 00151, Italy;5. Department of Oral and Maxillofacial Science, “La Sapienza” University of Rome, Via Caserta 272/A, Rome, Italy
Abstract:BackgroundRenal cell carcinoma (RCC) accounts for 3 % of cancer patients. Early detection influences the therapeutic strategy and significantly improves patients’ survival rates. Stable existing circulating miRNAs could be a promising diagnostic biomarker.MethodsPreviously our team demonstrated the anti-tumor effect of miR-20b-5p, miR-30a-5p and miR-196a-5p in RCC tissue and cell lines. Here, based on 110 RCC patients and 110 health control, we investigated serum expression of these three miRNAs in the testing set and the validation set separately by using quantitative real-time PCR. A three-miRNA panel with high diagnostic efficiency was constructed. Correlations between these miRNAs and clinical parameters were investigated. Additionally, the TCGA dataset and bioinformatic analysis are used for the functional exploration of these miRNAs.ResultsSerum expression levels of miR-20b-5p, miR-30a-5p were significantly reduced in RCC patients, while miR-196a-5p expression level was up-regulated (p < 0.001). miR-20b-5p, miR-30a-5p and miR-196a-5p had moderate diagnostic ability for RCC (AUC = 0.807, 0.766 and 0.719 in the testing set, respectively). The AUC of the three-miRNA panel was 0.949 in the testing set and 0.938 in the validation set. Specifically, the serum expression level of miR-196a-5p was significantly down-regulated in RCC patients with higher Fuhrman grade (p = 0.051). TCGA dataset analysis showed that the three-miRNA panel probably participated in RCC by targeting ITGA4 and NRP2.ConclusionThe three-miRNA panel could serve as a promising non-invasive biomarker for RCC detection.
Keywords:miR-20b-5p  miR-30a-5p  miR-196a-5p  Renal cell carcinoma  Biomarker  Noninvasive
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