MicroRNA-profiling of miR-371~373- and miR-302/367-clusters in serum and cerebrospinal fluid identify patients with intracranial germ cell tumors
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 bioma...
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Published in | Journal of cancer research and clinical oncology Vol. 149; no. 2; pp. 791 - 802 |
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Main Authors | , , , , , , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Berlin/Heidelberg
Springer Berlin Heidelberg
01.02.2023
Springer Nature B.V |
Subjects | |
Online Access | Get full text |
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Summary: | 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. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0171-5216 1432-1335 |
DOI: | 10.1007/s00432-022-03915-4 |