MicroRNA-profiling of miR-371 similar to 373-and miR-302/367-clusters in serum and cerebrospinal fluid identify patients with intracranial germ cell tumors

Schoenberger, Stefan and Mohseni, Mahsa Mir and Ellinger, Joerg and Tran, Giao Vu Quynh and Becker, Martina and Claviez, Alexander and Classen, Carl-Friedrich and Hermes, Barbara and Driever, Pablo Hernaiz and Jorch, Norbert and Lauten, Melchior and Mehlitz, Marcus and Schaefer, Niklas and Scheer-Preiss, Johanna and Schneider, Dominik T. and Troeger, Anja and Calaminus, Gabriele and Dilloo, Dagmar (2023) MicroRNA-profiling of miR-371 similar to 373-and miR-302/367-clusters in serum and cerebrospinal fluid identify patients with intracranial germ cell tumors. JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY, 149 (2). pp. 791-802. ISSN 0171-5216, 1432-1335

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Abstract

Purpose Intracranial germ cell tumors (iGCT) comprise germinoma and non-germinoma. Their diagnosis predominantly relies on biopsy as only one-fifth of patients present with elevated biomarkers (AFP/beta-HCG) in serum or cerebrospinal fluid (CSF). MicroRNAs (miR/miRNA) have emerged as non-invasive biomarkers in extracranial GCT and may potentially facilitate non-invasive diagnosis in iGCT. Methods We analyzed eight miRNAs in serum and CSF from the miR-371 similar to 373- and miR-302/367-clusters and four miRNAs differentially expressed in iGCT tissue (miR-142-5p/miR-146a-5p/miR-335-5p/miR-654-3p) from eight iGCT patients (age 10-33 years) and 12 control subjects by pre-amplified RT-qPCR. MiR-30b-5p (serum) and miR-204-5p (CSF) acted as reference genes. Delta C-t-values were expressed as 2(-Delta)(Delta Ct) after standardization against controls. Results Between iGCT and control patients' serum C t -values of miR-371a-3p (p = 0.0159), miR-372-3p (p= 0.0095, miR367 (p = 0.0190), miR-302a (p = 0.0381) and miR-302d-3p (p = 0.0159) differed significantly. Discriminatory pattern in CSF was similar to serum as miR-371a (p = 0.0286), miR-372-3p (p = 0.0028), miR-367-3p (p = 0.0167) and miR-302d-3p (p = 0.0061) distinguished between patients and controls. Abundant 2(-Delta)(Delta C)(t) levels of each of these miRNAs were found across all serum and CSF samples including biomarker-negative patients. Conclusion With the largest data set so far, we underline the suitability of miR-371a, miR-372, miR-367 and miR-302d in serum and CSF for diagnosis of iGCT, particularly in biomarker-negative germinoma. Diagnosis of iGCT by miRNA analysis is a feasible and valid approach, particularly as serum can be readily obtained by a less invasive procedure. MiRNA analysis may discriminate iGCT from other tumors with similar radiological findings and may allow to monitor response to therapy as well as early relapse during follow-up.

Item Type: Article
Uncontrolled Keywords: CENTRAL-NERVOUS-SYSTEM; EXPRESSION; CNS; DIAGNOSIS; BIOMARKER; Intracranial germ cell tumors; Liquid biopsy; miR-371; miR-372; miR-367; miR-302d
Subjects: 600 Technology > 610 Medical sciences Medicine
Divisions: Medicine > Abteilung für Pädiatrische Hämatologie, Onkologie und Stammzelltransplantation
Depositing User: Dr. Gernot Deinzer
Date Deposited: 05 Mar 2024 13:54
Last Modified: 05 Mar 2024 13:54
URI: https://pred.uni-regensburg.de/id/eprint/58668

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