Preview

South Russian Journal of Cancer

Advanced search

Urine transcriptomic profile in terms of malignant ovarian tumors

https://doi.org/10.37748/2686-9039-2024-5-3-7

EDN: ZOVXQO

Abstract

Purpose of the study. Bioinformatic search for transcriptomic markers (based on metabolomic data) and their validation in the urine of serous ovarian adenocarcinoma patients.

Materials and methods. The study included 70 patients with serous ovarian adenocarcinoma and 30 conditionally healthy individuals. The search for metabolite regulator genes and gene regulator microRNAs was performed using the Random forest machine learning method. Ribonucleic acid (RNA) was isolated using the RNeasy Plus Universal Kits. The level of microRNA transcripts in urine was determined by real-time PCR. Differences were assessed using the Mann-Whitney test with Bonferroni correction.

Results. Using the Random forest method, metabolite-regulator gene (47 genes) and metabolite-regulator microRNA (613 unique microRNA) relationships were established. The identified microRNAs were validated by real-time PCR. Changes in the levels of microRNA transcripts were detected: miR-382-5p, miR-593-3p, miR-29a-5p, miR-2110, miR-30c-5p, miR-181a-5p, let-7b-5p, miR-27a-3p, miR-370-3p, miR-6529-5p, miR-653-5p, miR-4742-5p, miR-2467-3p, miR-1909-5p, miR-6743-5p, miR-875-3p, miR-19a-3p, miR-208a-5p, miR-330-5p, miR-1207-5p, miR-4668-3p, miR-3193, miR-23a-3p, miR-12132, miR-765, miR-181b-5p, miR-4529-3p, miR-33b-5p, miR-17-5p, miR-6866-3p, miR-4753-5p, miR-103a-3p, miR-423-5p, miR-491-5p, miR-196b-5p, miR-6843-3p, miR-423-5p and miR-3184-5p in the urine of patients compared to conditionally healthy individuals.

Conclusion. Thus, urine transcriptome profiling allowed both to identify potential disease markers and to better understand the molecular mechanisms of changes underlying ovarian cancer development.

About the Authors

D. S. Kutilin
National Medical Research Centre for Oncology
Russian Federation

Denis S. Kutilin – Cand. Sci. (Biol.), Leading Researcher, Laboratory of Molecular Oncology, National Medical Research Centre for Oncology, Rostov-on-Don, Russian Federation

ORCID: https://orcid.org/0000-0002-8942-3733, SPIN: 8382-4460, AuthorID: 794680, Scopus Author ID: 55328886800


Competing Interests:

the authors declare that there are no obvious and potential conflicts of interest associated with the publication of this article



F. E. Filippov
Clinical Oncology Dispensary No. 1
Russian Federation

Fedor E. Filippov – oncologist of the Department of Oncogynecology, Clinical Oncology Dispensary No. 1, Krasnodar, Russian Federation


Competing Interests:

the authors declare that there are no obvious and potential conflicts of interest associated with the publication of this article



N. V. Porhanova
Clinical Oncology Dispensary No. 1
Russian Federation

Natalya V. Porhanova – Dr. Sci. (Med.), Associate Professor of the Department of Oncology, oncologist, Clinical Oncology Dispensary No. 1, Krasnodar, Russian Federation

SPIN: 2611-4840, AuthorID: 589928


Competing Interests:

the authors declare that there are no obvious and potential conflicts of interest associated with the publication of this article



A. Yu. Maksimov
National Medical Research Centre for Oncology
Russian Federation

Aleksey Yu. Maksimov – Dr. Sci. (Med.), Professor, Deputy General Director, National Medical Research Centre for Oncology, Rostov-on-Don, Russian Federation

ORCID: https://orcid.org/0000-0002-9471-3903, SPIN: 7322-5589, AuthorID: 710705, Scopus Author ID: 56579049500


Competing Interests:

the authors declare that there are no obvious and potential conflicts of interest associated with the publication of this article



References

1. Reid BM, Permuth JB, Sellers TA. Epidemiology of ovarian cancer: a review. Cancer Biol Med. 2017 Feb;14(1):9–32. https://doi.org/10.20892/j.issn.2095-3941.2016.0084

2. Злокачественные новообразования в России в 2018 году (заболеваемость и смертность). Под ред. А. Д. Каприна, В. В. Старинского, Г. В. Петровой. М.: МНИОИ им. П. А. Герцена – филиал ФГБУ «НМИЦ радиологии» Минздрава России, 2019, 250 с.

3. Цандекова М. Р., Порханова Н. В., Кутилин Д. С. Молекулярная характеристика серозной аденокарциномы яичника: значение для диагностики и лечения. Современные проблемы науки и образования. 2020;(1):55. https://doi.org/10.17513/spno.29428, EDN: LTMXTL

4. Meinhold-Heerlein I, Fotopoulou C, Harter P, Kurzeder C, Mustea A, Wimberger P, et al. The new WHO classification of ovarian, fallopian tube, and primary peritoneal cancer and its clinical implications. Arch Gynecol Obstet. 2016 Apr;293(4):695–700. https://doi.org/10.1007/s00404-016-4035-8

5. Rooth C. Ovarian cancer: risk factors, treatment and management. Br J Nurs. 2013 Sep 12;22(17):S23–30. https://doi.org/10.12968/bjon.2013.22.Sup17.S23

6. Swiatly A, Plewa S, Matysiak J, Kokot ZJ. Mass spectrometry-based proteomics techniques and their application in ovarian cancer research. J Ovarian Res. 2018 Oct 1;11(1):88. https://doi.org/10.1186/s13048-018-0460-6

7. Veenstra TD. Metabolomics: the final frontier? Genome Med. 2012 Apr 30;4(4):40. https://doi.org/10.1186/gm339

8. Гуськова О. Н., Аллилуев И. А., Вереникина Е. В., Половодова В. В., Рогозин М. А., Мягкова Т. Ю. и др. Изменение концентрации метаболитов в моче как малоинвазивный маркер серозной аденокарциномы яичников. Российский биотерапевтический журнал. 2023;22(3):43–50. https://doi.org/10.17650/1726-9784-2023-22-3-43-50, EDN: KRLBXC

9. Schmidt DR, Patel R, Kirsch DG, Lewis CA, Vander Heiden MG, Locasale JW. Metabolomics in cancer research and emerging applications in clinical oncology. CA Cancer J Clin. 2021 Jul;71(4):333–358. https://doi.org/10.3322/caac.21670

10. Димитриади Т. А., Бурцев Д. В., Дженкова Е. А., Кутилин Д. С. МикроРНК как маркеры прогрессирования предраковых заболеваний в рак шейки матки. Современные проблемы науки и образования. 2020;(1):99. https://doi.org/10.17513/spno.29529, EDN: SPESSH

11. Abdelsattar ZM, Wong SL, Regenbogen SE, Jomaa DM, Hardiman KM, Hendren S. Colorectal cancer outcomes and treatment patterns in patients too young for average-risk screening. Cancer. 2016 Mar 15;122(6):929–934. https://doi.org/10.1002/cncr.29716

12. Balcells I, Cirera S, Busk PK. Specific and sensitive quantitative RT-PCR of miRNAs with DNA primers. BMC Biotechnol. 2011 Jun 25;11:70. https://doi.org/10.1186/1472-6750-11-70

13. Vandesompele J, De Preter K, Pattyn F, Poppe B, Van Roy N, De Paepe A, et al. Accurate normalization of real-time quantitative RT-PCR data by geometric averaging of multiple internal control genes. Genome Biol. 2002 Jun 18;3(7):RESEARCH0034. https://doi.org/10.1186/gb-2002-3-7-research0034

14. Peltier HJ, Latham GJ. Normalization of microRNA expression levels in quantitative RT-PCR assays: identification of suitable reference RNA targets in normal and cancerous human solid tissues. RNA. 2008 May;14(5):844–852. https://doi.org/10.1261/rna.939908

15. Shen Y, Li Y, Ye F, Wang F, Wan X, Lu W, et al. Identification of miR-23a as a novel microRNA normalizer for relative quantification in human uterine cervical tissues. Exp Mol Med. 2011 Jun 30;43(6):358–366. https://doi.org/10.3858/emm.2011.43.6.039

16. Кутилин Д. С., Димитриади С. Н., Водолажский Д. И., Франциянц Е. М., Кит О. И. Влияние тепловой ишемии-реперфузии на экспрессию апоптоз-регулирующих генов в почечной ткани больных с почечно-клеточным раком. Нефрология. 2017;21(1):80–86. https://doi.org/10.24884/1561-6274-2017-21-1-80-86, EDN: XVGWWP

17. Jones E, Oliphant E, Peterson P. SciPy: Open source scientific tools for python. 2001.

18. Ding J, Li X, Hu H. TarPmiR: a new approach for microRNA target site prediction. Bioinformatics. 2016 Sep 15;32(18):2768–2775. https://doi.org/10.1093/bioinformatics/btw318

19. Цандекова М. Р., Порханова Н. В., Кит О. И., Кутилин Д. С. Малоинвазивная молекулярная диагностика серозной аденокарциномы яичника высокой и низкой степени злокачественности. Онкогинекология. 2021;(4(40):35–50. https://doi.org/10.52313/22278710_2021_4_35, EDN: ACKKXS

20. Li Y, Yao L, Liu F, Hong J, Chen L, Zhang B, et al. Characterization of microRNA expression in serous ovarian carcinoma. Int J Mol Med. 2014 Aug;34(2):491–498. https://doi.org/10.3892/ijmm.2014.1813

21. Han Y, Zheng Y, You J, Han Y, Lu X, Wang X, et al. Hsa_circ_0001535 inhibits the proliferation and migration of ovarian cancer by sponging miR-593-3p, upregulating PTEN expression. Clin Transl Oncol. 2023 Oct;25(10):2901–2910. https://doi.org/10.1007/s12094-023-03152-2

22. Resnick KE, Alder H, Hagan JP, Richardson DL, Croce CM, Cohn DE. The detection of differentially expressed microRNAs from the serum of ovarian cancer patients using a novel real-time PCR platform. Gynecol Oncol. 2009 Jan;112(1):55–59. https://doi.org/10.1016/j.ygyno.2008.08.036

23. Kwon JJ, Factora TD, Dey S, Kota J. A Systematic Review of miR-29 in Cancer. Mol Ther Oncolytics. 2019 Mar 29;12:173–194. https://doi.org/10.1016/j.omto.2018.12.011

24. Wu Q, Li G, Gong L, Cai J, Chen L, Xu X, et al. Identification of miR-30c-5p as a tumor suppressor by targeting the m6 A reader HNRNPA2B1 in ovarian cancer. Cancer Med. 2023 Feb;12(4):5055–5070. https://doi.org/10.1002/cam4.5246

25. Zhou J, Gong G, Tan H, Dai F, Zhu X, Chen Y, et al. Urinary microRNA-30a-5p is a potential biomarker for ovarian serous adenocarcinoma. Oncol Rep. 2015 Jun;33(6):2915–2923. https://doi.org/10.3892/or.2015.3937

26. Gasparri ML, Casorelli A, Bardhi E, Besharat AR, Savone D, Ruscito I, et al. Beyond circulating microRNA biomarkers: Urinary microRNAs in ovarian and breast cancer. Tumour Biol. 2017 May;39(5):1010428317695525. https://doi.org/10.1177/1010428317695525


Supplementary files

Review

For citations:


Kutilin D.S., Filippov F.E., Porhanova N.V., Maksimov A.Yu. Urine transcriptomic profile in terms of malignant ovarian tumors. South Russian Journal of Cancer. 2024;5(3):76-90. https://doi.org/10.37748/2686-9039-2024-5-3-7. EDN: ZOVXQO

Views: 207


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


ISSN 2686-9039 (Online)