Preview

Research and Practical Medicine Journal

Advanced search

Analysis of Gene Expression Omnibus high-throughput sequencing data for the determination of microribonucleic acids in the blood plasma of patients with glioblastomas

https://doi.org/10.17709/2410-1893-2022-9-1-5

Abstract

Purpose of the study. This work is devoted to the study of blood plasma miRNA patterns in blood plasma using high-throughput sequencing of the Omnibus Gene Expression base and the search for candidate miRNA molecules for the development of a minimally invasive diagnostic panel.

Materials and methods. Basing on the open dataset of Omnibus Expression of the NCBI GSE150956 Gene, groups of samples with glioblastoma and conventionally healthy donors were formed. For each sample, information on the levels of miRNA expression was extracted. Determination of significant miRNAs using machine learning algorithms of the R 4.0.4 project. For significant miRNAs, target genes have been performed, an analysis of the improvement of functional characteristics and interactome analysis of target genes of miRNA were performed.

Results. The study analyzed the data of 131 samples, where 35 samples with glioblastoma and 96 samples of the conditionally healthy group. Differential expression data were obtained for 945 miRNA. Two panels were obtained using machine learning methods, common miRNA – hsa-miR 3180, hsa-miR 3180-3p, hsa-miR 6782-5p, hsa-miR 182-5p, hsa-miR 133b and hsa-miR 670-3p. For significant miRNAs, information was obtained on experimentally confirmed target genes, a gene ontology demonstrating their participation in enzyme binding, participation in the regulation of primary cellular metabolic processes, and the development of glioblastomas and cancer in general.

Conclusion. As a result of layer-by-layer filtering and application of machine learning algorithms, significant miRNAs were identified that are candidates for a diagnostic panel of a minimally invasive method of high-grade glial tumors.

About the Authors

A. A. Pushkin
National Medical Research Centre for Oncology
Russian Federation

Anton A. Pushkin – Researcher, Laboratory of Molecular Oncology, SPIN: 9223-1871, AuthorID: 975797, ResearcherID: AAA-8887-2020, Scopus Author ID: 57200548010

63 14 line str., Rostov-on-Don 344037, Russian Federation



D. Yu. Gvaldin
National Medical Research Centre for Oncology
Russian Federation

Dmitry Yu. Gvaldin – Cand. Sci. (Biol.), Researcher, Laboratory of Molecular Oncology, SPIN: 8426-9283, AuthorID: 1010353, ResearcherID: AAA-9894-2020, Scopus Author ID: 57195716861

Rostov-on-Don



N. N. Timoshkina
National Medical Research Centre for Oncology
Russian Federation

Natalya N. Timoshkina – Cand. Sci. (Biol.), Head of the Laboratory Molecular Oncology, SPIN: 9483-4330, AuthorID: 633651, ResearcherID: D-3876-2018, Scopus Author ID: 24077206000

Rostov-on-Don



E. E. Rostorguev
National Medical Research Centre for Oncology
Russian Federation

Eduard E. Rostorguev – Dr. Sci. (Med.), head of Neurooncology Department, SPIN: 8487-9157, Author ID: 794808, Researcher ID: AAK-6852-2020, Scopus Author ID: 57196005138

Rostov-on-Don



L. Yu. Vladimirova
National Medical Research Centre for Oncology
Russian Federation

Lubov Yu. Vladimirova – Dr. Sci. (Med.), professor, head of the department of antitumor Drug Therapy No. 1, Head of Tumor drug Therapy Department, SPIN: 4857-6202, AuthorID: 289090, ResearcherID: U-8132-2019, Scopus Author ID: 7004401163

Rostov-on-Don



E. A. Dzenkova
National Medical Research Centre for Oncology
Russian Federation

Elena A. Dzhenkova – Dr. Sci. (Biol.), Associate Professor, academic secretary, SPIN: 6206-6222, AuthorID: 697354, ResearcherID: K-9622-2014, Scopus Author ID: 6507889745

Rostov-on-Don



References

1. Kit O I, Vodolazhsky D I, Rostorguev E E, Porksheyan D H, Panina S B. The role of micro-RNA in the regulation of signal pathways in gliomas. Biomeditsinskaya Khimiya. 2017;63(6):481–498. (In Russ.). https://doi.org/10.18097/PBMC20176306481

2. Malignant neoplasms in Russia in 2018 (morbidity and mortality). Ed. by Kaprina AD, Starinskogo VV, Petrova GV. Moscow, 2019. Available at: https://oncology-association.ru/wp-content/uploads/2020/09/2018.pdf. Accessed: 28.12.2021. (In Russ.).

3. Alliluyev I A, Pushkin A A, Kuznetsova N S, Kavitsky S E, Rostorguev E E. Estimation of the diagnostic significance of circulating micrornas in blood plasma of patients with high grade gliomas. Modern Problems of Science and Education. 2020;(6):135–135. (In Russ.). https://doi.org/10.17513/spno.30309

4. Shkurat T P, Pushkin A A, Kozlova M Yu, Kalina E A, Prokudina I O. Bioinformatic research of miRNA regulators of tumor suppressor genes. Materials of the VI conference Actual problems of biology, nanotechnology and medicine. Rostov-on-Don, 2015, 64–65 p. Available at: https://hub.sfedu.ru/repository/material/800820188/. Accessed: 28.12.2021. (In Russ.).

5. Gvaldin D Y, Pushkin A A, Timoshkina N N, Rostorguev E E, Nalgiev A M, Kit O I. Integrative analysis of mRNA and miRNA sequencing data for gliomas of various grades. Egyptian Journal of Medical Human Genetics. 2020;21(1):1–17. (In Russ.). https://doi.org/10.1186/s43042-020-00119-8

6. Kit OI, Vodolazhsky DI, Rostorguev EE, Frantsyants EM, Panina SB. Molecular genetic markers of gliomas. Molecular genetics, microbiology and virology. 2017;35(4):132–140. (In Russ.). https://doi.org/10.18821/0208-0613-2017-35-4-132-140

7. Xu S, Wang J, Ding N, Hu W, Zhang X, Wang B, et al. Exosome-mediated microRNA transfer plays a role in radiation-induced bystander effect. RNA Biol. 2015;12(12):1355–1363. https://doi.org/10.1080/15476286.2015.1100795

8. Kit O I, Rastorguev E E, Timoshkina N N, Pushkin A A, Alliluyev I A, Kuznetsova N S, etc. A method for diagnosing glial brain tumors of a high degree of malignancy. Patent RU 2742413 C1. Available at: https://patents.s3.yandex.net/RU2742413C1_20210205.pdf. Accessed: 01.02.2022. (In Russ.).

9. Yang C, Wang C, Chen X, Chen S, Zhang Y, Zhi F, et al. Identification of seven serum microRNAs from a genome-wide serum microRNA expression profile as potential noninvasive biomarkers for malignant astrocytomas. Int J Cancer. 2013 Jan 1;132(1):116–127. https://doi.org/10.1002/ijc.27657

10. Qu S, Guan J, Liu Y. Identification of microRNAs as novel biomarkers for glioma detection: a meta-analysis based on 11 articles. J Neurol Sci. 2015 Jan 15;348(1–2):181–187. https://doi.org/10.1016/j.jns.2014.11.036

11. Roth P, Wischhusen J, Happold C, Chandran PA, Hofer S, Eisele G, et al. A specific miRNA signature in the peripheral blood of glioblastoma patients. J Neurochem. 2011 Aug;118(3):449–457. https://doi.org/10.1111/j.1471-4159.2011.07307.x

12. Aparicio-Puerta E, Lebrón R, Rueda A, Gómez-Martín C, Giannoukakos S, Jaspez D, et al. sRNAbench and sRNAtoolbox 2019: intuitive fast small RNA profiling and differential expression. Nucleic Acids Res. 2019 Jul 2;47(W1):W530–W535. https://doi.org/10.1093/nar/gkz415

13. Robin X, Turck N, Hainard A, Tiberti N, Lisacek F, Sanchez J-C, et al. pROC: an open-source package for R and S+ to analyze and compare ROC curves. BMC Bioinformatics. 2011 Mar 17;12:77. https://doi.org/10.1186/1471-2105-12-77

14. Kuhn M. A Short Introduction to the caret Package. R Found Stat Comput, 2015, 1–10 p.

15. Ru Y, Kechris KJ, Tabakoff B, Hoffman P, Radcliffe RA, Bowler R, et al. The multiMiR R package and database: integration of microRNA-target interactions along with their disease and drug associations. Nucleic Acids Res. 2014;42(17):e133. https://doi.org/10.1093/nar/gku631

16. Hamberg M, Backes C, Fehlmann T, Hart M, Meder B, Meese E, et al. MiRTargetLink–miRNAs, Genes and Interaction Networks. Int J Mol Sci. 2016 Apr 14;17(4):564. https://doi.org/10.3390/ijms17040564

17. Kolberg L, Raudvere U, Kuzmin I, Vilo J, Peterson H. gprofiler2 -- an R package for gene list functional enrichment analysis and namespace conversion toolset g:Profiler. F1000Res. 2020;9:ELIXIR-709. https://doi.org/10.12688/f1000research.24956.2

18. Zhang H, Cong Q-X, Zhang S-G, Zhai X-W, Li H-F, Li S-Q. High Expression Levels of Fascin-1 Protein in Human Gliomas and its Clinical Relevance. Open Med (Wars). 2018;13:544–550. https://doi.org/10.1515/med-2018-0080

19. Fan Y, Potdar AA, Gong Y, Eswarappa SM, Donnola S, Lathia JD, et al. Profilin-1 phosphorylation directs angiocrine expression and glioblastoma progression through HIF-1α accumulation. Nat Cell Biol. 2014 May;16(5):445–456. https://doi.org/10.1038/ncb2954

20. Chen T, Liu Y, Chen J, Zheng H, Chen Q, Zhao J. Exosomal miR-3180-3p inhibits proliferation and metastasis of non-small cell lung cancer by downregulating FOXP4. Thorac Cancer. 2021 Feb;12(3):372–381. https://doi.org/10.1111/1759-7714.13759

21. Jin L, Zhang Z. Serum miR-3180-3p and miR-124-3p may Function as Noninvasive Biomarkers of Cisplatin Resistance in Gastric Cancer. Clin Lab. 2020 Dec 1;66(12). https://doi.org/10.7754/Clin.Lab.2020.200302

22. Mørup N, Stakaitis R, Golubickaite I, Riera M, Dalgaard MD, Schierup MH, et al. Small RNAs in Seminal Plasma as Novel Biomarkers for Germ Cell Tumors. Cancers (Basel). 2021 May 13;13(10):2346. https://doi.org/10.3390/cancers13102346

23. Gao L, Yan S-B, Yang J, Kong J-L, Shi K, Ma F-C, et al. MiR-182-5p and its target HOXA9 in non-small cell lung cancer: a clinical and in-silico exploration with the combination of RT-qPCR, miRNA-seq and miRNA-chip. BMC Med Genomics. 2020 Jan 6;13(1):3. https://doi.org/10.1186/s12920-019-0648-7

24. Wen D, Li S, Ji F, Cao H, Jiang W, Zhu J, et al. miR-133b acts as a tumor suppressor and negatively regulates FGFR1 in gastric cancer. Tumour Biol. 2013 Apr;34(2):793–803.


Supplementary files

Review

For citations:


Pushkin A.A., Gvaldin D.Yu., Timoshkina N.N., Rostorguev E.E., Vladimirova L.Yu., Dzenkova E.A. Analysis of Gene Expression Omnibus high-throughput sequencing data for the determination of microribonucleic acids in the blood plasma of patients with glioblastomas. Research and Practical Medicine Journal. 2022;9(1):54-64. (In Russ.) https://doi.org/10.17709/2410-1893-2022-9-1-5

Views: 504


Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.


ISSN 2410-1893 (Online)