MicroRNA-profiling of miR-371~373- and miR-302/367-clusters in serum and cerebrospinal fluid identify patients with intracranial germ cell tumors
Journal of cancer research and clinical oncology(2022)
摘要
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^ - ΔΔ 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^ - ΔΔ 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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关键词
Intracranial germ cell tumors,Liquid biopsy,miR-302d,miR-367,miR-371,miR-372
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