Alireza Tabibkhooei1, Maryam Izadpanahi2, Abolfazl Arab3, Ali Zare-Mirzaei4, Sara Minaeian5, Ali Rostami6, Alireza Mohsenian6. 1. Department of Neurosurgery, Iran University of Medical Sciences, Tehran, Iran. Electronic address: Tabibkhooei.a@iums.ac.ir. 2. Department of Neurosurgery, Iran University of Medical Sciences, Tehran, Iran. Electronic address: science_izadpanahi@yahoo.com. 3. Faculty of New Sciences and Technologies, University of Tehran, Tehran, Iran. 4. Department of Pathology, Iran University of Medical Sciences, Tehran, Iran. 5. Antimicrobial Resistance Research Center, Institute of Immunology and Infection Diseases, Iran University of Medical Sciences, Tehran, Iran. 6. Department of Neurosurgery, Iran University of Medical Sciences, Tehran, Iran.
Abstract
OBJECTIVE: Glioblastoma (GBM) is the most common primary malignant neoplasm of the central nervous system (CNS). Despite the progress in therapeutic strategies such as surgical techniques, radiotherapy, chemotherapy, and targeted therapy, prognosis and therapeutically convenient monitoring tools in patients with GBM has not improved significantly up to now.Therefore, exosomal miRNAs as novel non-invasive biomarkers having high sensitivity and specificity are required to improve diagnosis and to develop new targeted therapy strategies for GBM patients. The aim of the present study was to investigate a novel miRNA signature as a predictive biomarker for diagnosis and measurement of response to therapeutic interventions in plasma of GBM patients versus traumatic brain injury and diffuse low-grade astrocytoma (LGA) patients. PATIENTS AND METHODS: Plasma exosomal-microRNAs were isolated from GBM (n = 25), LGA (n = 25), and head trauma patients (n = 15) as non-glioma control from March 2017 to June 2018 in Department of Neurosurgery at Rasoul-e-Akram Hospital. Through a bioinformatics analysis, we used Miranda, TargetScan, mirBase, DIANA-microT-CDS, and KEGG database as well as microarray data analysis from GEO for microRNA candidates. Finally, miR-210, miR-185, miR-5194, and miR-449 were selected among those miRNAs because they were recorded to target the maximum number of genes in EGFR and c-MET signaling pathways. Then, exosomal microRNAs were extracted from plasma of patients and quantitated by locked nucleic acid real-time PCR in GBM, LGA, and trauma patients. RESULTS: This result is the first report on the role of circulating miR-185, miR-449, and miR-5194 in GBM compared to LGA and trauma. The plasma expression of miR-210 as an oncogenic miR was upregulated in GBM and LGA groups (P < 0.0001). Otherwise, miR-185, miR-5194, and miR-449 were significantly downregulated (P ≤ 0.05) in GBM and LGA compared to trauma patients. There was no significant downregulation in the expression of miR-185 between GBM and LGA, while the expression of miR-5194 (P ≤ 0.05) and miR-449 (P ≤ 0.05) was significantly decreased in GBM patients compared with LGA. CONCLUSIONS: These results indicate that the levels of miR-210, miR-449, and miR-5194 are a promising diagnostic and prognostic biomarker positively correlated with histopathological grade and invasiveness of GBM. These findings imply that circulating microRNA can be potentially used as novel biomarkers for glioma that might be beneficial in clinical management of glioma patients.
OBJECTIVE:Glioblastoma (GBM) is the most common primary malignant neoplasm of the central nervous system (CNS). Despite the progress in therapeutic strategies such as surgical techniques, radiotherapy, chemotherapy, and targeted therapy, prognosis and therapeutically convenient monitoring tools in patients with GBM has not improved significantly up to now.Therefore, exosomal miRNAs as novel non-invasive biomarkers having high sensitivity and specificity are required to improve diagnosis and to develop new targeted therapy strategies for GBMpatients. The aim of the present study was to investigate a novel miRNA signature as a predictive biomarker for diagnosis and measurement of response to therapeutic interventions in plasma of GBMpatients versus traumatic brain injury and diffuse low-grade astrocytoma (LGA) patients. PATIENTS AND METHODS: Plasma exosomal-microRNAs were isolated from GBM (n = 25), LGA (n = 25), and head traumapatients (n = 15) as non-glioma control from March 2017 to June 2018 in Department of Neurosurgery at Rasoul-e-Akram Hospital. Through a bioinformatics analysis, we used Miranda, TargetScan, mirBase, DIANA-microT-CDS, and KEGG database as well as microarray data analysis from GEO for microRNA candidates. Finally, miR-210, miR-185, miR-5194, and miR-449 were selected among those miRNAs because they were recorded to target the maximum number of genes in EGFR and c-MET signaling pathways. Then, exosomal microRNAs were extracted from plasma of patients and quantitated by locked nucleic acid real-time PCR in GBM, LGA, and traumapatients. RESULTS: This result is the first report on the role of circulating miR-185, miR-449, and miR-5194 in GBM compared to LGA and trauma. The plasma expression of miR-210 as an oncogenic miR was upregulated in GBM and LGA groups (P < 0.0001). Otherwise, miR-185, miR-5194, and miR-449 were significantly downregulated (P ≤ 0.05) in GBM and LGA compared to traumapatients. There was no significant downregulation in the expression of miR-185 between GBM and LGA, while the expression of miR-5194 (P ≤ 0.05) and miR-449 (P ≤ 0.05) was significantly decreased in GBMpatients compared with LGA. CONCLUSIONS: These results indicate that the levels of miR-210, miR-449, and miR-5194 are a promising diagnostic and prognostic biomarker positively correlated with histopathological grade and invasiveness of GBM. These findings imply that circulating microRNA can be potentially used as novel biomarkers for glioma that might be beneficial in clinical management of gliomapatients.
Authors: Igea D'Agnano; Carlo Cenciarelli; Hany E Marei; Asmaa Althani; Nahla Afifi; Anwarul Hasan; Thomas Caceci; Ingrid Cifola; Sara Caratelli; Giuseppe Sconocchia Journal: Discov Oncol Date: 2022-06-18
Authors: Pinar Uysal-Onganer; Amy MacLatchy; Rayan Mahmoud; Igor Kraev; Paul R Thompson; Jameel M Inal; Sigrun Lange Journal: Int J Mol Sci Date: 2020-02-22 Impact factor: 5.923