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

• Published in: Journal of cancer research and clinical oncology Vol. 149; no. 2; pp. 791 - 802
• Main Authors: Schönberger, Stefan, Mohseni, Mahsa Mir, Ellinger, Jörg, Tran, Giao Vu Quynh, Becker, Martina, Claviez, Alexander, Classen, Carl-Friedrich, Hermes, Barbara, Driever, Pablo Hernáiz, Jorch, Norbert, Lauten, Melchior, Mehlitz, Marcus, Schäfer, Niklas, Scheer-Preiss, Johanna, Schneider, Dominik T., Troeger, Anja, Calaminus, Gabriele, Dilloo, Dagmar
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.02.2023; Springer Nature B.V
• Subjects: Adolescent; Adult; Biomarkers; Biomarkers, Tumor - genetics; Biopsy; blood serum; Cancer Research; Cerebrospinal fluid; Child; data collection; Diagnosis; germ cells; Germinoma - genetics; Hematology; Humans; Internal Medicine; Medicine; Medicine & Public Health; microRNA; MicroRNAs; MicroRNAs - genetics; miRNA; Neoplasm Recurrence, Local; Oncology; Original Article – Clinical Oncology; Original – Clinical Oncology; relapse; Standardization; Tumors; Young Adult; miR-367; Liquid biopsy; miR-371; miR-372; miR-302d; Intracranial germ cell tumors
• DOI: 10.1007/s00432-022-03915-4
• ISSN: 0171-5216; 1432-1335

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/ß-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-371~373- 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. Δ C t -values were expressed as 2 - Δ Δ C t after standardization against controls. Results Between iGCT and control patients’ serum Δ C t -values of miR-371a-3p ( p  = 0.0159), miR-372-3p ( p = 0.0095, miR-367 ( 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 - Δ Δ 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.