Evaluation of MicroRNA Expressions in Ovarian Cancer
Objectives: The present study aims to evaluate the relationship between microribonucleic acid (miRNA) and target gene expressions with clinical and histopathological data in ovarian cancer.
Methods: We evaluated 96 archival samples of paraffin-embedded tissue. Some potentially significant miRNA and target gene expressions were evaluated in different histopathological characteristics. These were quantified using realtime–polymerase chain reaction (RT–PCR) in tumor and normal tissue. In miRNA expressions, twofold changes are accepted as significant.
Results: According to histopathological groups, 38 (39.6%) were endometroid adenocarcinoma, 11 (11.5%) were borderline serous, 29 (30.2%) were serous, and 18 (18.8%) were mucinous carcinoma. When evaluated according to their stages, 26 (27.1%) patients were stage 1A/1B. A relationship was found between miR200a and miR200c and histopathologic groups, between miR141 and estrogen receptors, between CXCL1 and survival status, and between KEAP1 and ki67. Additionally, miR200a in endometrial and miR200c in mucinous adenocarcinoma were overexpressed. When the relationship between all miRNAs and histopathological groups was evaluated, a significant change was found only in miR200c expression. It was significantly higher in serous than endometrial tumors and significantly higher in mucinous than endometroid tumors.
Conclusion: These suggested that miR200a and 200c expressions might be useful for the evaluation of histopathological subgroups of ovarian cancer.
1. Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer statistics, 2021. A Cancer J Clin 2021;71:7–33. [CrossRef]
2. Noone AM, Howlader N, Krapcho M, Miller D, Brest A, Yu M, et al. SEER cancer statistics review, 1975-2015, National Cancer Institute. Based on November 2017 SEER data submission, posted to the SEER web site, April 2018. Available at: https://seer.cancer.gov/archive/csr/1975_2015/. Accessed Dec 8, 2022.
3. Torre LA, Trabert B, DeSantis CE, Miller KD, Samimi G, Runowicz CD, et al. Ovarian cancer statistics. CA Cancer J Clin 2018;68:284–96. [CrossRef]
4. Robboy SJ. Robboy's pathology of the female reproductive tract. 2nd ed. London: Churchill Livingstone; 2008.
5. James NE, Chichester C, Ribeiro JR. Beyond the biomarker: understanding the diverse roles of human epididymis protein 4 in the pathogenesis of epithelial ovarian cancer. Front Oncol 2018;8:124. [CrossRef]
6. Dochez V, Caillon H, Vaucel E, Dimet J, Winer N, Ducarme G. Biomarkers and algorithms for diagnosis of ovarian cancer: CA125, HE4, RMI and ROMA, a review. J Ovarian Res 2019;12:28. [CrossRef]
7. Hwang HW, Mendell JT. MicroRNAs in cell proliferation, cell death, and tumorigenesis. Br J Cancer 2006;94:776–80.
8. Esquela-Kerscher A, Slack FJ. Oncomirs - microRNAs with a role in cancer. Nat Rev Cancer 2006;6:259–69. [CrossRef]
9. Christodoulatos GS, Dalamaga M. Micro-RNAs as clinical biomarkers and therapeutic targets in breast cancer: Quo vadis? World J Clin Oncol 2014;5:71–81. [CrossRef]
10. Zhong X, Coukos G, Zhang L. miRNAs in human cancer. Methods Mol Biol 2012;822:295–306.
11. Wang X, Ivan M, Hawkins SM. The role of MicroRNA molecules and MicroRNA-regulating machinery in the pathogenesis and progression of epithelial ovarian cancer. Gynecol Oncol 2017;147:481–7.
12. Weidle UH, Birzele F, Kollmorgen G, Nopora A. Potential microRNA-related target for therapeutic intervention with ovarian cancer metastasis. Cancer Genomics Proteomics 2018;15:1–15 [CrossRef]
13. Deb B, Uddin A, Chakraborty S. miRNAs and ovarian cancer: An overview. J Cell Physiol 2018;233:3846–54. [CrossRef]
14. Yavuzsen HT, Aktas S, Saatli BH, Altun ZS. MicroRNA’s in ovarian cancer. DEÜ Tıp Fakültesi Dergisi 2019;33:93–101.
15. Shi M, Mu Y, Zhang H, Liu M, Wan J, Qin X, et al. MicroRNA-200 and microRNA-30 family as prognostic molecular signatures in ovarian cancer: A meta-analysis. Medicine (Baltimore) 2018;97:e11505. [CrossRef]
16. Xing Z, Li D, Yang L, Xi Y, Su X. MicroRNAs and anticancer drugs. Acta Biochim Biophys Sin 2014;46:233–9.
17. Wiemer AC. The role of microRNAs in cancer: No small matter. Eur J Cancer 2007;43:1529–44. [CrossRef]
18. Duska LR, Park WP, Moore KN. Epithelial ovarian cancer in older women: defining the best managenment approach. Am Soc Clin Oncol Educ Book 2015;e311–21. [CrossRef]
19. Cavallari I, Ciccarese F, Sharova E, Urso L, Raimondi V, Silic-Benussi M, et al. The miR-200 Family of microRNAs: Fine tuners of epithelial-mesenchymal transition and circulating cancer biomarkers. Cancers (Basel) 2021;13:5874.
20. Zuberi M, Mir R, Das J, Ahmad I, Javid J, Yadav P, et al. Expression of serum miR-200a, miR-200b, and miR-200c as candidate biomarkers in epithelial ovarian cancer and their association with clinicopathological features. Clin Transl Oncol 2015;17:779–87.
21. Wang X, Seed B. A PCR primer bank for quantitative gene expression analysis. Nucleic Acids Res 2003;31:e154. [CrossRef]
22. Hulstaert E, Morlion A, Levanon K, Vandesompele J, Mestdagh P. Candidate RNA biomarkers in biofluids for early diagnosis of ovarian cancer: A systematic review. Gynecol Oncol 2021;160:633–42
23. Iorio MV, Visone R, Di Leva G, Donati V, Petrocca F, Casalini P, et al. MicroRNA signatures in human ovarian cancer. Cancer Res 2007;67:8699–707. [CrossRef]
24. Mateescu B, Batista L, Cardon M, Gruosso T, de Feraudy Y, Mariani O, et al. miR-141 and miR-200a act on ovarian tumorigenesis by controlling oxidative stress response, Nat Med 2011;17:1627–35. [CrossRef]
25. Suo HB, Zhang KC, Zhao J. MiR-200a promotes cell invasion and migration of ovarian carcinoma by targeting PTEN, Eur Rev Med Pharmacol Sci 2018;22:4080–89.
26. Guan W, Cui H, Huang P, Chun WJ, Lee JW, Kim H, et al. miR200b/200a/429 cluster stimulates ovarian cancer development by targeting ING5. J Oncol 2020;2020:3404059.
27. Lu YM, Shang C, Ou YL, Yin D, Li YN, Li X, et al. miR-200c modulates ovarian cancer cell metastasis potential by targeting zinc finger E-box-binding homeobox 2 (ZEB2) expression. Med Oncol 2014;31:134. [CrossRef]
28. Sadlecki P, Jozwicki J, Antosik P, Grabiec M. Expression of selected epithelial–mesenchymal transition transcription factors in serous borderline ovarian tumors and type I ovarian cancers. Tumor Biology 2018;40:1010428318784807
29. Chen R, Zhang M, Liu W, Chen H, Cai T, Xiong H, et al. Estrogen affects the negative feedback loop of PTENP1-miR200c to inhibit PTEN expression in the development of endometrioid endometrial carcinoma. Cell Death Dis 2018;10:4. [CrossRef]
30. Liew PL, Hsu CS, Liu WM, Lee YC, Lee YC, Chen CL. Prognostic and predictive values of Nrf2, Keap1, p16 and E-cadherin expression in ovarian epithelial carcinoma. Int J Clin Exp Pathol 2015;8:5642–49.
31. Konstantinopoulos PA, Spentzos D, Fountzilas E, Francoeur N, Sanisetty S, Grammatikos AP, et al. Keap1 mutations and Nrf2 patthway activation in epithelial ovarian cancer. Cancer Res 2011;71:5081–89.
32. van Jaarsveld MTM, Helleman J, Boersma AWM, van Kuijk PF, Despierre E, Vergote I, et al. miR-141 regulates KEAP1 and modulates cisplatin sensitivity in ovarian cancer cells. Oncogene 2013;32:4284–93. [CrossRef]
33. Ouh YT, Cho HW, Lee JK, Choi SH, Choi HJ, Hong JH. CXC chemokine ligand 1 mediates adiponectin-induced angiogenesis in ovarian cancer. Tumour Biol 2019;42:1010428319842699.