SIGNIFICANCE OF miRNA-185-5P AND miRNA-424-5P AS PROGNOSTIC MARKERS IN PROGRESSION OF EARLY-STAGE ENDOMETRIAL CANCER

Authors

  • N.P. IURCHENKO R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, National Academy of Sciences of Ukraine, Kyiv, Ukraine
  • N.M. GLUSHCHENKO R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, National Academy of Sciences of Ukraine, Kyiv, Ukraine
  • S.V. NESPRYADKO SNE “National Cancer Institute”, Kyiv, Ukraine
  • L.G. BUCHYNSKA R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, National Academy of Sciences of Ukraine, Kyiv, Ukraine

DOI:

https://doi.org/10.15407/exp-oncology.2024.03.244

Keywords:

endometrioid carcinoma of endometrium, miRNA-185-5p and miRNA-424-5p expression, peripheral blood serum, relapses

Abstract

Aim. To compare the expression of miRNA-185-5p and miRNA-424-5p in tumor cells and peripheral blood serum (PBS) of patients with endometrioid carcinoma of the endometrium (ECE) and to evaluate the significance of these biomarkers in cancer progression. Materials and Methods. The study was conducted on the samples of peripheral blood serum (PBS) and tumor tissue of 58 patients with stage I ECE using clinical and morphological methods and real-time polymerase chain reaction. Results. A significant increase in the levels of circulating and tumor-associated miRNA-424-5p was established in ECE patients with a history of recurrences compared to patients without recurrences. To the contrary, the expression level of miRNA-185-5p increased in the PBS and decreased in the tumor tissue of ECE patients with recurrences compared to the patients without recurrence. In addition, we revealed that the expression levels of the studied miRNAs were associated with the differentiation grade and degree of tumor invasion. We established that miRNA-424-5p levels in PBS could serve as the most significant indicator for predicting the occurrence of recurrence in patients with ECE (AUC = 0.991; Sp 94.0%; Se 99.9%). Conclusions. The expression features of miRNA-185-5p and miRNA-424-5p in the PBS and tumor tissue of patients with ECE are associated with the aggressiveness of cancer course and the risk of recurrence.

References

Soslow RA, Tornos C, Park KJ, et al. Endometrial carcinoma diagnosis: use of FIGO grading and genomic subcat­ egories in clinical practice: recommendations of the international society of gynecological pathologists. Int J Gynecol Pathol. 2019;38Suppl1(Iss1Suppl1):S64­S74. https://doi.org/10.1097/PGP.0000000000000518

Murali R, Davidson B, Fadare O, et al. High­grade endometrial carcinomas: morphologic and immunohistochemical features, diagnostic challenges and recommendations. Int J Gynecol Pathol. 2019;38 Suppl1(Iss 1 Suppl 1):S40­S63. https://doi.org/10.1097/PGP.0000000000000491

Buchynska LG, Glushchenko NM, Nesina IP, et al. Molecular phenotype of high­grade endometrioid carcinoma of the endometrium. Exp Oncol. 2020;42(4):300­305. https://doi.org/10.32471/exp­oncology.2312­8852.vol­42­no­4.15450

Buchynska LG, Glushchenko NM, Nespryadko SV, et al. The significance of the expression of the epithelial­mes­ enchymal transition marker Snail1 and its regulator TGF­β1 in the progression of endometrioid carcinoma of the endometry. Oncology. 2023;25(3):194­199. https://doi.org/10.15407/oncology.2023.03.194 (in Ukrainian).

Buchynska L, Gordiienko I, Glushchenko N, Iurchenko N. The KRAS, ATR and CHEK1 expression levels in endo­ metrial cancer are the risk factors predicting recurrence. PLoS One. 2024,26;19(4):e0302075. https://doi.org/10.1371/ journal.pone.0302075

Cancer Genome Atlas Research Network; Kandoth C, Schultz N, Cherniack AD, et al. Integrated genomic character­ ization of endometrial carcinoma. Nature. 2013;497(7447):67­73. https://doi.org/10.1038/nature12113

Concin N, Matias­Guiu X, Vergote I, et al. ESGO/ESTRO/ESP guidelines for the management of patients with endo­ metrial carcinoma. Int J Gynecol Cancer. 2021;31:12­39. https://doi.org/10.1136/ijgc­2020­002230

Smith HL, Southgate H, Tweddle DA, Curtin NJ. DNA damage checkpoint kinases in cancer. Expert Rev Mol Med. 2020;22:e2. https://doi.org/10.1017/erm.2020.3

Kabeche L, Nguyen HD, Buisson, R, Zou L. A mitosis­specific and R loop–driven ATR pathway promotes faithful chromosome segregation. Science. 2018;359(6371):108­114. https://doi.org/10.1126/science.aan6490

Gralewska P, Gajek A, Marczak A, Rogalska A. Participation of the ATR/CHK1 pathway in replicative stress targeted therapy of high­grade ovarian cancer. J Hematol Oncol. 2020;13(1):39. https://doi.org/10.1186/s13045­020­00874­6

Vessoni AT, Zhang T, Quinet A. et al. Telomere erosion in human pluripotent stem cells leads to atr­mediated mitotic catastrophe. J Cell Biol. 2021;20(6):e202011014. https://doi.org/10.1083/jcb.202011014

Ferragut Cardoso AP, Banerjee M, Nail AN, et al. miRNA dysregulation is an emerging modulator of genomic insta­ bility. Semin Cancer Biol. 2021;76:120­131. https://doi.org/10.1016/j.semcancer.2021.05.004

Peng Y, Croce CM. The role of microRNAs in human cancer. Signal Transduct Target Ther. 2016;1:15004. https://doi. org/10.1038/sigtrans.2015.4

Pełka K, Klicka K, Grzywa TM, et al. miR­96­5p, miR­134­5p, miR­181b­5p and miR­200b­3p heterogenous ex­ pression in sites of prostate cancer versus benign prostate hyperplasia­archival samples study. Histochem Cell Biol. 2021;155:423­433. https://doi.org/10.1007/s00418­020­01941­2

Lekka E, Hall J. Noncoding RNAs in disease. FEBS Lett. 2018;592(17):2884­2900. https://doi.org/10.1002/1873­3468.13182

Irmak­Yazicioglu MB. Mechanisms of microRNA deregulation and microRNA targets in gastric cancer. Oncol Res Treat. 2016;39(3):136­139. https://doi.org/10.1159/000443224

Buchynska LG, Borykun TV, Iurchenko NP, et al. Expression of microRNA in tumor cells of endmetrioid carci­ noma of endometrium. Exp Oncol. 2020;42(4):289­294. https://doi.org/10.32471/exp­oncology.2312­8852.vol­42­ no­4.15522

Galvão­Lima LJ, Morais AHF, Valentim RAM, Barreto EJSS. miRNAs as biomarkers for early cancer detection and their application in the development of new diagnostic tools. Biomed Eng Online. 2021;20(1):21. https://doi. org/10.1186/s12938­021­00857­9

Babaeenezhad E, Naghibalhossaini F, Rajabibaz M, et al. The roles of microRNA miR­185 in digestive tract. Cancers Noncoding RNA. 2022;8(5):67. https://doi.org/10.3390/ncrna8050067

Wang R, Tian S, Wang HB, et al. MiR­185 is involved in human breast carcinogenesis by targeting Vegfa. FEBS Lett. 2014;588(23):4438­4447. https://doi.org/10.1016/j.febslet.2014.09.045

Zhi Q, Zhu J, Guo X, et al. Metastasis­related miR­185 is a potential prognostic biomarker for hepatocellular carci­ noma in early stage. Biomed Pharmacother. 2013;67(5):393­398. https://doi.org/10.1016/j.biopha.2013.03.022

Zhang K, Wang YY, Xu Y, et al. A two­miRNA signature of upregulated miR­185­5p and miR­362­5p as a blood biomarker for breast cancer. Pathol Res Pract. 2021;222:153458. https://doi.org/10.1016/j.prp.2021.153458

Shi YJ, Fang YX, Tian TG, et al. Discovery of extracellular vesicle­delivered miR­185­5p in the plasma of patients as an indicator for advanced adenoma and colorectal cancer. J Transl Med. 2023;21(1):421. https://doi.org/10.1186/ s12967­023­04249­6

Boren T, Xiong Y, Hakam A, et al. MicroRNAs and their target messenger RNAs associated with endometrial carci­ nogenesis. Gynecol Oncol. 2008;110(2):206­215. https://doi.org/10.1016/j.ygyno.2008.03.023

Yanokura M, Banno K, Iida M, et al. MicroRNAS in endometrial cancer: recent advances and potential clinical ap­ plications. EXCLI J. 2015;14:190­198. https://doi.org/10.17179/excli2014­590

Dai W, Zhou J, Wang H, et al. miR­424­5p promotes the proliferation and metastasis of colorectal cancer by directly targeting SCN4B. Pathol Res Pract. 2020;216(1):152731. https://doi.org/10.1016/j.prp.2019.152731

Liu J, Gu Z, Tang Y, et al. Tumour­suppressive microRNA­424­5p directly targets CCNE1 as potential prognostic markers in epithelial ovarian cancer. Cell Cycle. 2018;17(3):309­318. https://doi.org/10.1080/15384101.2017.1407894

Wang J, Wang S, Zhou J, Qian Q. miR­424­5p regulates cell proliferation, migration and invasion by targeting dou­ blecortin­like kinase1 in basal­like breast cancer. Biomed Pharmacother. 2018;102:147­152. https://doi.org/10.1016/j. biopha.2018.03.018

Du H, Xu Q, Xiao S, et al. MicroRNA­424­5p acts as a potential biomarker and inhibits proliferation and invasion in hepatocellular carcinoma by targeting TRIM29. Life Sci. 2019;224:1­11. https://doi.org/10.1016/j.lfs.2019.03.028

Xu SJ, Xu WJ, Zeng Z, Zhang M, Zhang DY. MiR­424 functions as potential diagnostic and prognostic biomarker in melanoma. Clin Lab. 2020;66(7). https://doi.org/10.7754/Clin.Lab.2019.190917

Delangle R, De Foucher T, Larsen AK, et al. The use of microRNAs in the management of endometrial cancer: a meta­analysis. Cancers (Basel). 2019;11(6):832. https://doi.org/10.3390/cancers11060832

Kurman RJ, Carcangiu ML, Herrington CS, Young RH. WHO Classification of Tumours of Female Reproductive Or- gans. Lyon: IARC, 2014. 307 p.

Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real­time quantitative PCR and the 2(­Delta Delta C(T)) method. Methods. 2001;25(4):402­408. https://doi.org/10.1006/meth.2001.1262

Wang T, Wang G, Zhang X, et al. The expression of miRNAs is associated with tumour genome instability and pre­ dicts the outcome of ovarian cancer patients treated with platinum agents. Sci Rep. 2017;7(1):14736. https://doi. org/10.1038/s41598­017­12259­w

Gajek A., Gralewska P, Marczak A, Rogalska A. Current implications of microRNAs in genome stability and stress responses of ovarian cancer. Cancers (Basel). 2021;13(11):2690. https://doi.org/10.3390/cancers13112690

Östling P, Leivonen SK, Aakula A, et al. Systematic analysis of microRNAs targeting the androgen receptor in pros­ tate cancer cells. Cancer Res. 2011;71(5):1956­1967. https://doi.org/10.1158/0008­5472.CAN­10­2421

Iurchenko NP, Glushchenko NM, Buchynska LG. Assessment of DNA status and peculiarities of expression of cy­ clins D1, E1 and transcription factor E2F1 in cells of epithelial endometrial tumors. Oncology. 2019;21(3):230­237. https://doi.org/10.32471/oncology.2663­7928.t­21­3­2019­g.7783 (in Ukrainian).

Wen J, Hu Y, Liu Q, et al. miR­424 coordinates multilayered regulation of cell cycle progression to promote esoph­ ageal squamous cell carcinoma cell proliferation. eBioMedicine. 2018;37:110­124. https://doi.org/10.1016/j.ebi­ om.2018.10.043

Schuhn A, Tobar WT, Gahlawat WA, et al. Potential of blood­based biomarker approaches in endometrium and breast cancer: a case­control comparison study. Arch Gynecol Obstet. 2022;306(5):1623­1632. https://doi.org/10.1007/ s00404­022­06482­8

Zhou L, Wang W, Wang F, et al. Plasma­derived exosomal miR­15a­5p as a promising diagnostic biomarker for early detection of endometrial carcinoma. Mol Cancer. 2021;20(1):57. https://doi.org/10.1186/s12943­021­01352­4

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Published

19.12.2024

How to Cite

IURCHENKO, N., GLUSHCHENKO, N., NESPRYADKO, S., & BUCHYNSKA, L. (2024). SIGNIFICANCE OF miRNA-185-5P AND miRNA-424-5P AS PROGNOSTIC MARKERS IN PROGRESSION OF EARLY-STAGE ENDOMETRIAL CANCER. Experimental Oncology, 46(3), 244–252. https://doi.org/10.15407/exp-oncology.2024.03.244

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