Research Article
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Meme kanserli hastalarda 20 serum mirna’nın klinikopatolojik değişkenler ile ilişkisi

Year 2023, , 168 - 178, 05.04.2023
https://doi.org/10.31362/patd.1216451

Abstract

Amaç: MiRNA’ların meme kanseri patogenezinde rol oynadığının belirlenmesi, meme kanserinin tanı ve tedavisinde yararlı olabileceğini düşündürmektedir.
Gereç ve yöntem: Toplanan 39 invaziv meme kanserli hasta serumundan mikroRNA’lar izole edildi ve cDNA’lara dönüştürüldü. Hastaların tanı anında ve tedavi sonrasında alınan kanlarından, 20 miRNA’nın (miR-105, miR-21, miR-141, miR-200a, miR-200b, miR-200c, miR-203, miR-210, miR-375, miR-34a, miR-133a, miR-155, miR-139-5p, miR-143, miR-145, miR-365, miR-299-5p, miR-411, miR-452 ve miR-17) serum düzeyleri analiz edildi.
Bulgular: Analiz sonuçlarında, miR-200c (p=0.030), miR-375 (p=0.045), miR-34a’nın (p=0.042) serum düzeyleri lokal ileri/metastatik grupta anlamlı olarak yüksek saptandı. miR-141’in (p=0.062) serum seviyesi lenf nodu tutulumu pozitif hastalarda daha düşük gözlenirken, miR-133a (p=0.037) seviyelerinin aynı hasta grubunda daha yüksek olduğu tespit edildi. MiR-105 (p=0.015), miR-203 (p=0.015), miR-375 (p=0.033), miR-145 (p=0.025) serum seviyelerinin PR negatif grupta belirgin yüksek olduğu, aynı şekilde miR-105 (p=0.053) seviyelerinin ER negatif grupta yüksek olduğu görüldü. Her 2 pozitif hastalarda miR-375 ve miR-133a seviyelerinin yüksekliği dikkat çekti (p=0.037 ve p=0.014, sırasıyla). MiR-143 (p=0.009) ve miR-145 (p=0.017) seviyelerinin ki-67 indeksi >%20 olan hasta grubunda daha yüksek olduğu ve bu miRNA’ların ki-67 indeksi ile korelasyon gösterdiği gözlendi (p=0.007; p=0.015, sırasıyla). Moleküler alt gruplara göre ayrılan hastalardan luminal B grubunda olanlarda 2 miRNA’nın (miRNA-133a (p=0.018) ve miRNA-139-5p (p=0.004)) anlamlı olarak daha yüksek olduğu saptandı. Çalışılan miRNA’lardan 9 tanesinin (miRNA-105 (p=0.0001), miRNA-21 (p=0.001), miRNA-141 (p=0.041), miRNA-200a (p=0.003), miRNA-200b (p=0.0001), miRNA-200c (p=0.0001), miRNA-203 (p=0.0001), miRNA-34a (p=0.0001), miRNA-452 (p=0.018)) tedavi sonrasında anlamlı olarak arttığı, 5 tanesinin (miRNA-155 (p=0.0001), miRNA-143 (p=0.0001), miRNA-145 (p=0.0001), miRNA-365 (p=0.0001), miRNA-299-5p (p=0.0001)) tedavi sonrasında anlamlı olarak azaldığı görüldü.
Sonuç: Sonuçlarımızın, invaziv meme kanserinin takibi ve prognozunu değerlendirmede yol gösterici olabileceğini düşünmekteyiz.

Supporting Institution

PAMUKKALE ÜNİVERSİTESİ BAP

Project Number

2018TIP025

References

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  • 12. Madhavan D, Peng C, Wallwiener M, et al. Circulating miRNAs with prognostic value in metastatic breast cancer and for early detection of metastasis. Carcinogenesis 2016;37:461-470. https://doi.org/10.1093/carcin/bgw008
  • 13. Simonini PSR, Breiling A, Gupta N, et al. Epigenetically Deregulated microRNA-375 Is involved in a positive feedback loop with estrogen receptor α in breast cancer cells. Cancer Res 2010;70:9175-9184. https://doi.org/10.1158/0008-5472.CAN-10-1318
  • 14. Li P, Xu T, Zhou X, et al. Downregulation of miRNA-141 in breast cancer cells is associated with cell migration and invasion: involvement of ANP32E targeting. Cancer Medicine 2017;6:662-672. https://doi.org/10.1002/cam4.1024
  • 15. Shimono Y, Ugalde MZ, Cho RW, et al. Down-regulation of miRNA-200c links breast cancer stem cells with normal stem cells. Cell 2009;138:592-603. https://doi.org/10.1016/j.cell.2009.07.011
  • 16. Sui Y, Zhang X, Yang H, Wei W, Wang M. Micro-RNA-133a acts as a tumour suppressor in breast cancer through targeting LASP1. Oncology Reports 2018;39:473-482. https://doi.org/10.3892/or.2017.6114
  • 17. Wu ZS, Wang CQ, Xiang R, et al. Loss of miR-133a expression associated with poor survival of breast cancer and restoration of miR-133a expression inhibited breast cancer cell growth and invasion. BMC Cancer 2012;12:51. https://doi.org/10.1186/1471-2407-12-51
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  • 20. Piasecka D, Braun M, Kordek R, Sadej R, Romanska H. MicroRNAs in regulation of triple-negative breast cancer progression. Journal of Cancer Research and Clinical Oncology 2018;144:1401-1411. https://doi.org/10.1007/s00432-018-2689-2
  • 21. Li HY, Liang JL, Kuo YL, et al. MiR-105/93-3p promotes chemoresistance and circulating miR-105/93-3p acts as a diagnostic biomarker for triple negative breast cancer, Breast Cancer Res 2017;19:133. https://doi.org/10.1186/s13058-017-0918-2 22. Yu X, Zhang X, Dhakal IB, Beggs M, Kadlubar S, Luo D. Induction of cell proliferation and survival genes by estradiol-repressed microRNAs in breast cancer cells. BMC Cancer 2012;12:29. https://doi.org/10.1186/1471-2407-12-29
  • 23. Han JG, Jiang YD, Zhang CH, et al. A novel panel of serum miR-21/miR-155/miR-365 as a potential diagnostic biomarker for breast cancer. Ann Surg Treat Res 2017;92:55-66. https://doi.org/10.4174/astr.2017.92.2.55
  • 24. Ye XM, Zhu HY, Bai WD, et al. Epigenetic silencing of miR-375 induces trastuzumab resistance in HER2 positive breast cancer by targeting IGF1R BMC Cancer 2014;14:134. https://doi.org/10.1186/1471-2407-14-134
  • 25. Li C, Li X, Gao S, Li C, Ma L. MicroRNA-133a inhibits proliferation of gastric cancer cells by downregulating ERBB2 expression. Oncology Research 2017;25:1169-1176. https://doi.org/10.3727/096504017X14847395834985
  • 26. Zhang HD, Sun DW, Mao L, et al. MiR-139-5p inhibits the biological function of breast cancer cells by targeting Notch1 and mediates chemosensitivity to docetaxel. Biochemical and Biophysical Research Communications 2015;465:702-713. https://doi.org/10.1016/j.bbrc.2015.08.053
  • 27. Hong L, Yang J, Han Y, Lu Q, Cao J, Syed L. High expression of miR-210 predicts poor survival in patients with breast cancer: a meta-analysis. Gene 2012;507:135-138. https://doi.org/10.1016/j.gene.2012.07.025
  • 28. Yan X, Chen X, Liang H, et al. miR-143 and miR-145 synergistically regulate ERBB3 to suppress cell proliferation and invasion in breast cancer. Mol Cancer 2014;13:220. https://doi.org/10.1186/1476-4598-13-220
  • 29. Freres P, Josse C, Bovy N, et al. Neoadjuvant chemotherapy in breast cancer patients induces miR-34a and miR-122 expression. J Cell Physiol 2015;230:473-481. https://doi.org/10.1002/jcp.24730
  • 30. Wang C, Zheng X, Shen C, Shi Y. MicroRNA-203 suppresses cell proliferation and migration by targeting BIRC5 and LASP1 in human triple-negative breast cancer cells Journal of Experimental & Clinical Cancer Research 2012;31:58. https://doi.org/10.1186/1756-9966-31-58
  • 31. Lin J, Wang L, Gao J, Zhu S. MiR‑203 inhibits estrogen‑induced viability, migration and invasion of estrogen receptor α‑positive breast cancer cells. Experimental and Therapeutic Medicine 2017;14:2702-2708. https://doi.org/10.3892/etm.2017.4828
  • 32. Li W, Li G, Fan Z, Liu T. Tumor-suppressive microRNA-452 inhibits migration and invasion of breast cancer cells by directly targeting RAB11A Oncology Letters 2017;14:2559-2565. https://doi.org/10.3892/ol.2017.6426
  • 33. Zhou W, Fong MY, Min Y, et al. Cancer-secreted miR-105 destroys vascular endothelial barriers to promote metastasis. Cancer Cell 2014;25:501-515. https://doi.org/10.1016/j.ccr.2014.03.007
  • 34. Si H, Sun X, Chen Y, et al. Circulating microRNA-92a and microRNA-21 as novel minimally invasive biomarkers for primary breast cancer. J Cancer Res Clin Oncol 2013;139:223-229. https://doi.org/10.1007/s00432-012-1315-y
  • 35. Sun Y, Wang M, Lin G, et al. Serum MicroRNA-155 as a potential biomarker to track disease in breast cancer. Plos One 2012;7:e47003. https://doi.org/10.1371/journal.pone.0047003
  • 36. Li M, Liu L, Zang W, et al. miR 365 overexpression promotes cell proliferation and invasion by targeting ADAMTS-1 in breast cancer. International Journal of Oncology 2015;47:296-302. https://doi.org/10.3892/ijo.2015.3015
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  • 38. Zhou LL, Dong JL, Huang G, Sun ZL, Wu J. MicroRNA-143 inhibits cell growth by targeting ERK5 and MAP3K7 in breast cancer. Braz J Med Biol Res 2017;50:e5891. https://doi.org/10.1590/1414-431X20175891
  • 39. Spizzo R, Nicoloso MS, Lupini L, et al. miR-145 participates with TP53 in a death-promoting regulatory loop and targets estrogen receptor-α in human breast cancer cells Cell Death and Differentiation 2010;17:246-254. https://doi.org/10.1038/cdd.2009.117
  • 40. Shevde LA, Metge BJ, Mitra A, et al. Spheroid-forming subpopulation of breast cancer cells demonstrates vasculogenic mimicry via hsa-miR-299-5p regulated de novo expression of osteopontin. J Cell Mol Med 2010;14:1693-1706. https://doi.org/10.1111/j.1582-4934.2009.00821.x

Association between 20 serum mirnas and clinicopathological variables in patients with breast cancer

Year 2023, , 168 - 178, 05.04.2023
https://doi.org/10.31362/patd.1216451

Abstract

Purpose: Determining microRNAs in breast cancer pathogenesis suggests that it may be beneficial for diagnosis and treatment.
Materials and methods: Patients serum were collected and microRNAs were isolated. Then microRNAs was converted to cDNA. After that, investigated serum levels of 20 microRNAs (miR-17, miR-21, miR-34a, miR-105, miR-133a, miR-139-5p, miR-141, miR-143, miR-145, miR-155, miR-200a, miR-200b, miR-200c, miR-203, miR-210, miR-299-5p, miR-365, miR-375, miR-411, miR-452) in 39 patients with invasive breast cancer were analyzed before and after treatment.
Results: In the analysis results, it is detected that serum levels of miR-200c, miR-375, miR-34a were markedly higher in the local advanced/metastatic group. MiR-141 levels was lower in patients with positive lymph node involvement, whereas miR-133a levels were higher in the same patient group. miR-105, miR-203, miR-375, miR-145 serum levels were markedly higher in the progesterone receptor negative group, likewise miR-105 levels were high in the estrogen receptor negative group. The high levels of miR-375 and miR-133a were noticeable in human epidermal growth factor receptor-2 positive patients. MiR-143 and miR-145 levels were observed higher in the patient with a ki-67 index >20%. It was found that 2 miRNAs (miR-133a and miR-139-5p) were markedly higher in patients in the luminal B group, which were separated by molecular subgroups. Nine of miRNAs that evaluated (miR-21, miR-34a, miR-105, miR-141, miR-200a, miR-200b, miR-200c, miR-203, miR-452) significantly increased and 5 of the miRNAs (miR-145, miR-365, miR-155, miR-143, miR-299-5p) were significantly reduced post-treatment.
Conclusion: We think that miRNAs may help in evaluating the follow-up and prognosis of invasive breast cancer.

Project Number

2018TIP025

References

  • 1. Calin GA, Sevignani C, Dan DC, et al. Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers. Proc Natl Acad Sci 2004;101:2999-3004. https://doi.org/10.1073/pnas.030732310
  • 2. Iorio MV, Crose CM. MicroRNA dysregulation in cancer: diagnostics, monitoring and therapeutics. A comprehensive review. EMBO Mol Med 2012;4:143-159. https://doi.org/10.1002/emmm.201100209
  • 3. McDermott AM, Miller N, Wall D, et al. Identification and validation of oncologic miRNA biomarkers for luminal A-like breast cancer. PLoS One 2014;9:e87032. https://doi.org/10.1371/journal.pone.0087032
  • 4. Di Leva G, Croce CM. Roles of small RNAs in tumor formation. Trends Mol Med 2010;16:257-267. https://doi.org/10.1016/j.molmed.2010.04.001
  • 5. Chin LJ, Slack FJ. A truth serum for cancer – MicroRNAs have majör potential as cancer biomarkers. Cell Res 2008;18:983‑984. https://doi.org/10.1038/cr.2008.290
  • 6. Jung EJ, Santarpia L, Kim J, et al. Plasma microRNA 210 levels correlate with sensitivity to trastuzumab and tumor presence in breast cancer patients. Cancer 2012;118:2603-2614. https://doi.org/10.1002/cncr.26565
  • 7. Marino ALF, Evangelista AF, Vieira RAC, et al. MicroRNA expression as risk biomarker of breast cancer metastasis: a pilot retrospective case-cohort study. BMC Cancer 2014;14:739. https://doi.org/10.1186/1471-2407-14-739
  • 8. Zhang L, Xu Y, Jin X, et al. A circulating miRNA signature as a diagnostic biomarker for non-invasive early detection of breast cancer. Breast Cancer Res Treat 2015;154:423-34. https://doi.org/10.1007/s10549-015-3591-0
  • 9. Madhavan D, Zucknick M, Wallwiener M, et al. Circulating miRNAs as surrogate markers for circulating tumor cells and prognostic markers in metastatic breast cancer. Clin Cancer Res 2012;18:5972-5982. https://doi.org/10.1158/1078-0432.CCR-12-1407
  • 10. Zhang G, Zhang W, Li B, et al. MicroRNA-200c and microRNA- 141 are regulated by a FOXP3-KAT2B axis and associated with tumor metastasis in breast cancer. Breast Cancer Research 2017;19:73. https://doi.org/10.1186/s13058-017-0858-x
  • 11. Roth C, Rack B, Müller V, Janni W, Pantel K, Schwarzenbach H. Circulating microRNAs as blood-based markers for patients with primary and metastatic breast cancer. Breast Cancer Research 2010;12:90. https://doi.org/10.1186/bcr2766
  • 12. Madhavan D, Peng C, Wallwiener M, et al. Circulating miRNAs with prognostic value in metastatic breast cancer and for early detection of metastasis. Carcinogenesis 2016;37:461-470. https://doi.org/10.1093/carcin/bgw008
  • 13. Simonini PSR, Breiling A, Gupta N, et al. Epigenetically Deregulated microRNA-375 Is involved in a positive feedback loop with estrogen receptor α in breast cancer cells. Cancer Res 2010;70:9175-9184. https://doi.org/10.1158/0008-5472.CAN-10-1318
  • 14. Li P, Xu T, Zhou X, et al. Downregulation of miRNA-141 in breast cancer cells is associated with cell migration and invasion: involvement of ANP32E targeting. Cancer Medicine 2017;6:662-672. https://doi.org/10.1002/cam4.1024
  • 15. Shimono Y, Ugalde MZ, Cho RW, et al. Down-regulation of miRNA-200c links breast cancer stem cells with normal stem cells. Cell 2009;138:592-603. https://doi.org/10.1016/j.cell.2009.07.011
  • 16. Sui Y, Zhang X, Yang H, Wei W, Wang M. Micro-RNA-133a acts as a tumour suppressor in breast cancer through targeting LASP1. Oncology Reports 2018;39:473-482. https://doi.org/10.3892/or.2017.6114
  • 17. Wu ZS, Wang CQ, Xiang R, et al. Loss of miR-133a expression associated with poor survival of breast cancer and restoration of miR-133a expression inhibited breast cancer cell growth and invasion. BMC Cancer 2012;12:51. https://doi.org/10.1186/1471-2407-12-51
  • 18. Blenkiron C, Goldstein LD, Thorne NP, et al. MicroRNA expression profiling of human breast cancer identifies new markers of tumor subtype. Genome Biol 2007;8:214. https://doi.org/10.1186/gb-2007-8-10-r214
  • 19. Lowery AJ, Miller N, Devaney A, et al. MicroRNA signatures predict oestrogen receptor, progesterone receptor and HER2/neu receptor status in breast cancer. Breast Cancer Res 2009;11:27. https://doi.org/10.1186/bcr2257
  • 20. Piasecka D, Braun M, Kordek R, Sadej R, Romanska H. MicroRNAs in regulation of triple-negative breast cancer progression. Journal of Cancer Research and Clinical Oncology 2018;144:1401-1411. https://doi.org/10.1007/s00432-018-2689-2
  • 21. Li HY, Liang JL, Kuo YL, et al. MiR-105/93-3p promotes chemoresistance and circulating miR-105/93-3p acts as a diagnostic biomarker for triple negative breast cancer, Breast Cancer Res 2017;19:133. https://doi.org/10.1186/s13058-017-0918-2 22. Yu X, Zhang X, Dhakal IB, Beggs M, Kadlubar S, Luo D. Induction of cell proliferation and survival genes by estradiol-repressed microRNAs in breast cancer cells. BMC Cancer 2012;12:29. https://doi.org/10.1186/1471-2407-12-29
  • 23. Han JG, Jiang YD, Zhang CH, et al. A novel panel of serum miR-21/miR-155/miR-365 as a potential diagnostic biomarker for breast cancer. Ann Surg Treat Res 2017;92:55-66. https://doi.org/10.4174/astr.2017.92.2.55
  • 24. Ye XM, Zhu HY, Bai WD, et al. Epigenetic silencing of miR-375 induces trastuzumab resistance in HER2 positive breast cancer by targeting IGF1R BMC Cancer 2014;14:134. https://doi.org/10.1186/1471-2407-14-134
  • 25. Li C, Li X, Gao S, Li C, Ma L. MicroRNA-133a inhibits proliferation of gastric cancer cells by downregulating ERBB2 expression. Oncology Research 2017;25:1169-1176. https://doi.org/10.3727/096504017X14847395834985
  • 26. Zhang HD, Sun DW, Mao L, et al. MiR-139-5p inhibits the biological function of breast cancer cells by targeting Notch1 and mediates chemosensitivity to docetaxel. Biochemical and Biophysical Research Communications 2015;465:702-713. https://doi.org/10.1016/j.bbrc.2015.08.053
  • 27. Hong L, Yang J, Han Y, Lu Q, Cao J, Syed L. High expression of miR-210 predicts poor survival in patients with breast cancer: a meta-analysis. Gene 2012;507:135-138. https://doi.org/10.1016/j.gene.2012.07.025
  • 28. Yan X, Chen X, Liang H, et al. miR-143 and miR-145 synergistically regulate ERBB3 to suppress cell proliferation and invasion in breast cancer. Mol Cancer 2014;13:220. https://doi.org/10.1186/1476-4598-13-220
  • 29. Freres P, Josse C, Bovy N, et al. Neoadjuvant chemotherapy in breast cancer patients induces miR-34a and miR-122 expression. J Cell Physiol 2015;230:473-481. https://doi.org/10.1002/jcp.24730
  • 30. Wang C, Zheng X, Shen C, Shi Y. MicroRNA-203 suppresses cell proliferation and migration by targeting BIRC5 and LASP1 in human triple-negative breast cancer cells Journal of Experimental & Clinical Cancer Research 2012;31:58. https://doi.org/10.1186/1756-9966-31-58
  • 31. Lin J, Wang L, Gao J, Zhu S. MiR‑203 inhibits estrogen‑induced viability, migration and invasion of estrogen receptor α‑positive breast cancer cells. Experimental and Therapeutic Medicine 2017;14:2702-2708. https://doi.org/10.3892/etm.2017.4828
  • 32. Li W, Li G, Fan Z, Liu T. Tumor-suppressive microRNA-452 inhibits migration and invasion of breast cancer cells by directly targeting RAB11A Oncology Letters 2017;14:2559-2565. https://doi.org/10.3892/ol.2017.6426
  • 33. Zhou W, Fong MY, Min Y, et al. Cancer-secreted miR-105 destroys vascular endothelial barriers to promote metastasis. Cancer Cell 2014;25:501-515. https://doi.org/10.1016/j.ccr.2014.03.007
  • 34. Si H, Sun X, Chen Y, et al. Circulating microRNA-92a and microRNA-21 as novel minimally invasive biomarkers for primary breast cancer. J Cancer Res Clin Oncol 2013;139:223-229. https://doi.org/10.1007/s00432-012-1315-y
  • 35. Sun Y, Wang M, Lin G, et al. Serum MicroRNA-155 as a potential biomarker to track disease in breast cancer. Plos One 2012;7:e47003. https://doi.org/10.1371/journal.pone.0047003
  • 36. Li M, Liu L, Zang W, et al. miR 365 overexpression promotes cell proliferation and invasion by targeting ADAMTS-1 in breast cancer. International Journal of Oncology 2015;47:296-302. https://doi.org/10.3892/ijo.2015.3015
  • 37. Gao W, Yu Y, Cao H et al. Deregulated expression of miR-21, miR-143 and miR-181a in non small cell lung cancer is related to clinicopathologic characteristics or patient prognosis. Biomed Pharmacother 2010;64:399-408. https://doi.org/10.1016/j.biopha.2010.01.018
  • 38. Zhou LL, Dong JL, Huang G, Sun ZL, Wu J. MicroRNA-143 inhibits cell growth by targeting ERK5 and MAP3K7 in breast cancer. Braz J Med Biol Res 2017;50:e5891. https://doi.org/10.1590/1414-431X20175891
  • 39. Spizzo R, Nicoloso MS, Lupini L, et al. miR-145 participates with TP53 in a death-promoting regulatory loop and targets estrogen receptor-α in human breast cancer cells Cell Death and Differentiation 2010;17:246-254. https://doi.org/10.1038/cdd.2009.117
  • 40. Shevde LA, Metge BJ, Mitra A, et al. Spheroid-forming subpopulation of breast cancer cells demonstrates vasculogenic mimicry via hsa-miR-299-5p regulated de novo expression of osteopontin. J Cell Mol Med 2010;14:1693-1706. https://doi.org/10.1111/j.1582-4934.2009.00821.x
There are 39 citations in total.

Details

Primary Language English
Subjects Oncology and Carcinogenesis
Journal Section Research Article
Authors

Açelya Gökdeniz Yıldırım 0000-0003-2932-3797

Aydın Demiray 0000-0002-3343-0184

Ali Can Koç 0000-0003-2481-7026

Hande Şenol 0000-0001-6395-7924

Arzu Yaren 0000-0003-1436-8650

Project Number 2018TIP025
Publication Date April 5, 2023
Submission Date December 10, 2022
Acceptance Date March 2, 2023
Published in Issue Year 2023

Cite

AMA Gökdeniz Yıldırım A, Demiray A, Koç AC, Şenol H, Yaren A. Association between 20 serum mirnas and clinicopathological variables in patients with breast cancer. Pam Tıp Derg. April 2023;16(2):168-178. doi:10.31362/patd.1216451
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