Comparison of serum and tissue values of miRNAs related to autophagy in glial brain tumors and metastases other than lmphoma

Aim: Central nervous system tumors are seen in both children and adults, and most of these tumors cause disability and death. Current studies are focused on the molecular pathogenesis to identify new targets for the diagnosis and follow-up of patients. In this study, we investigated whether serum micro ribonucleic acid (miRNA) values could be used as biomarkers of these tumors by examining miRNA levels associated with autophagy in serum and tissue.Material and Methods: We included 27 patients who underwent surgery at our clinic and were diagnosed with glial tumor or metastasis other than lymphoma after pathological examination. The serum and tissue levels of miRNAs associated with autophagy were compared, and correlations between the obtained values were determined using Student’s t-test.Results: Based on histopathological examination, there were 14 glioblastomas, 3 oligodendrogliomas, 2 anaplastic astrocytomas, 2 carcinoma metastases, 2 pilocytic astrocytomas, 1 anaplastic ependymoma, 1 anaplastic oligodendroglioma, 1 diffuse astrocytoma, and 1 ependymoma. Serum Ct values were significantly higher than tissue Ct values. Correlations were found between serum and tissue levels of 5 miRNA subtypes. In addition, we could not determine the Ct value in some serum samples for 5 of the 12 miRNA subtypes.Conclusion: Although correlations were found between serum and tissue miRNA levels in the literature, we did not find any reasonable correlation, which might be explained by the less number of patients in our study. Therefore, considering the results of this study, we believe it is too early to determine that miRNAs cannot be biomarkers of brain tumors.

PDF

___

1. Yu X, Li Z. Serum microRNAs as potential noninvasive biomarkers for glioma. Tumor Biol 2016; 37: 1407-10.
2. Garg N, Vijayakumar T, Bakhshinyan D, et al.. MicroRNA regulation of brain tumour initiating cells in central nervous system tumours. Stem Cells Int. 2015;2015:141793.
3. Shea A, Harish V, Afzal Z, et al. MicroRNAs in glioblastoma multiforme pathogenesis and Therapeutics. Cancer Med 2016;5:1917-46.
4. Luo JW, Wang X, Yang Y, et al. Role of micro-RNA (miRNA) in pathogenesis of glioblastoma. Eur Rev Med Pharmacol Sci 2015;19:1630-39.
5. Bustin SA, Mueller R. Real-time reverse transcription PCR (qRT-PCR) and its potential use in clinical diagnosis. Clin Sci 2005;109:365-79.
6. Brase JC, Wuttig D, Kuner R, et al. Serum microRNAs as noninvasive biomarkers for cancer. Mol Cancer 2010;9:306.
7. Lawrie CH, Gal S, Dunlop HM, et al. Detection of elevated levels of tumor associated microRNAs in serum of patients with diffuse large B-cell lymphoma. Br J Haematol 2008;141:672-5.
8. Gwak HS, Kim TH, Jo GH, et al. Silencing of microRNA-21 confers radio-sensitivity through inhibition of the PI3K/AKT pathway and enhancing autophagy in malignant glioma cell lines. PLoS One 2012;7:e47449.
9. Mitchell PS, Parkin RK, Kroh EM, et al. Circulating microRNAs as stable blood-based markers for cancer detection. Proc Natl Acad Sci USA 2008;105:10513-8.
10. Ng EK, Chong WW, Jin H, et al. Differential expression of microRNAs in plasma of patients with colorectal cancer: a potential marker for colorectal cancer screening. Gut 2009;58:1375-81.
11. Wang J, Yi X, Tang H, et al. Direct quantification of microRNA at low picomolar level in sera of glioma patients using a competitive hybridization followed by amplified voltammetric detection. Anal Chem 2012;84:6400-06.
12. Wu J, Li L, Jiang C. Identification and evaluation of serum microRNA-29 family for glioma screening. Mol Neurobiol 2015;52:1540-6.
13. Wei X, Chen D, Lv T, et al. Serum microRNA-125b as a potential biomarker for glioma diagnosis. Mol Neurobiol 2014;53:163-70.
14. Lai NS, Wu DG, Fang XG, et al. Serum microRNA-210 as a potential noninvasive biomarker for the diagnosis and prognosis of glioma. Br J Cancer 2015;112:1241-6.
15. Sun J, Liao K, Wu X, et al. Serum microRNA-128 as a biomarker for diagnosis of glioma. Int J Clin Exp Med 2015;8:456-63.
16. Lavon I, Zrihan D, Granit A, et al. Gliomas display a microRNA expression profile reminiscent of neural precursor cells. Neuro Oncol 2010;12:422-33.
17. Silber J, Lim DA, Petritsch C, et al. miR-124 and miR-137 inhibit proliferation of glioblastoma multiforme cells and induce differentiation of brain tumor stem cells. BMC Med 2008;6:14.
18. Yan W, Li R, Liu Y, et al. MicroRNA expression patterns in the malignant progression of gliomas and a 5- microRNA signature for prognosis. Oncotarget 2014;5:12908-15.
19. Møller HG, Rasmussen AP, Andersen HH, et al. A systematic review of microRNA in glioblastoma multiforme: micromodulators in the mesenchymal mode of migration and invasion. Mol Neurobiol 2013;47:131-44.
20. Comincini S, Allavena G, Palumbo S, et al. microRNA-17 regulates the expression of ATG7 and modulates the autophagy process, improving the sensitivity to temozolomide and low-dose ionizing radiation treatments in human glioblastoma cells. Cancer Biol Ther 2013;14:574-86.
21. Turchinovich A, Weiz L, Langheinz A, et al. Characterization of extracellular circulating microRNA. Nucleic Acids Res 2011;39:7223-33.