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MicroRNAs (miRNAs) are involved in the development and progression of malignant tumors. In breast cancer, differential miRNA expression has been demonstrated across breast cancer subtypes, with both tumor-promoting and tumor suppressive functions for individual miRNAs.
Novel predictive biomarkers that can be assessed in the liquid specimen before systemic treatment could help to individualize treatment decisions in breast cancer and to potentially avoid ineffective systemic treatment.
In our study we detect level of circulating miRNA 21 in breast cancer patient before and after neoadjuvant treatment , whether there will be change or not, and if related to complete pathological response.
MicroRNAs (miRNAs) are a group of non-coding, single stranded RNAs of ~ 19-24 nucleotides, which act by a novel mechanism of posttranscriptional regulation that is profoundly altered in malignant cells. (Ling, Fabbri and Calin, 2013).Based on the function of miRNAs, they are divided into two types: an oncomir, implicated in cancer progression by regulating tumor suppressor genes negatively; and a tumor suppressor, preventing cancers by regulating oncogenes. (Zhang et al., 2007).
A key oncomir in carcinogenesis is miRNA-21, which was one of the first miRNAs detected in the human genome. It is located on chromosome 17 in the tenth intron of the coding gene transmembrane protein 49, which targets various tumor suppressors like PTEN, PDCD4, p53, and TAp63 pathways. (Yadav et al., 2016)
Experimental and literature research has highlighted that miRNA-21 was always significantly elevated in every study that included invasive breast carcinomas compared with healthy breast tissue. (Petrović, 2016).
miRNA-21 has been shown to be a very important promoter of cellular outgrowth, migration, invasion, and metastasis. In breast carcinoma cell lines, miRNA-21 was connected to cell proliferation and migration. (Yan et al., 2011).
Mei and her colleagues (2010) reported that miRNA-21 up-regulation is associated with therapy (taxol) resistance in breast cancer cells and further validated in a recent study by (Chen and Bourguignon, 2014) in which miRNA-21 up-regulation resulted in an increase of anti-apoptosis protein BCL-2 and chemo-resistance in breast cancer cells
Various studies have supported the potential role of circulating miRNAs to be used as prognostic and predictor biomarkers in breast cancer. (Schwarzenbach, 2017)
In their analysis of the blood serum of 56 breast cancer patients, Wang et al. (2012) illustrate reduced miR-125b levels to correlate with resistance to four cycles of neoadjuvant 5-fluorouracil, epirubicin and cyclophosphamide (FEC). Another recent study investigating dynamic changes of circulating miRNA as indicator for clinical response for neoadjuvant chemotherapy in HER2 negative patients , found that dynamics of three plasma miRNA , including miRNA 222, miRNA 20-a and miRNA 451 was associated with chemosensitivity. (Zhu et al., 2018)
The expression of serum-miRNA-125b and the changes of serum miRNA-21 expression during neoadjuvant chemotherapy were associated with chemotherapy response and disease-free survival (DFS). (Liu et al., 2017). Yadav et al. (2016) found that breast cancer patients received neoadjuvant therapy shows significant impact on overall reduction in serum miRNA-21 expression compared to before therapy (p < 0.0001)
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Breast cancer patients eligible to neoadjuvant systemic therapy | Invasive breast cancer, age are 18 years or more, from stage IIB to stage IIIC, all subtypes are included, either HR (ER, PR) positive or negative, HER2 positive or negative, eligible to neoadjuvant systemic therapy. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| microRNA 21 | Diagnostic Test | Plasma microRNA 21 5p expression, by real-time polymerase chain reaction, before and after neoadjuvant systemic therapy. Blood sample will be taken by a trained nurse, amount of blood will be 3 ml, and will be taken twice, one time before the start of the neoadjuvant systemic treatment , second time by the end of the neoadjuvant systemic treatment. |
| Measure | Description | Time Frame |
|---|---|---|
| Describe miRNA 21 expression level before and after neoadjuvant systemic therapy in breast cancer patient. | miRNA 21 expression level before and after neoadjuvant systemic therapy | 1 year |
| Measure | Description | Time Frame |
|---|---|---|
| Measure relation between miRNA 21 expression level before and after neoadjuvant systemic therapy and pathological response. | Relation between miRNA 21 expression level before and after neoadjuvant systemic therapy and pathological response | 1 year |
| Measure relation between the miRNA 21 expression and the clinicopathological parameters of Breast Cancer patients. |
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Inclusion Criteria:
Exclusion Criteria:
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Invasive breast cancer, from stage IIB to stage IIIC, all subtypes are included, who are candidates for neoadjuvant systemic therapy.
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Ebtehal M Salah, MD | Contact | +201013678565 | ebtehal.mohamed@hotmail.com | |
| Iman A Sharawy, Phd | Contact | +201068280224 | emansharawy@gmail.com |
| Name | Affiliation | Role |
|---|---|---|
| Ebtehal M Salah | Assistant lecturer of clinical oncology | Principal Investigator |
| Iman Sharawy | Professor of clinical oncology | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Ain Shams University Hospitals | Cairo | Egypt |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 20082533 | Result | Mei M, Ren Y, Zhou X, Yuan XB, Han L, Wang GX, Jia Z, Pu PY, Kang CS, Yao Z. Downregulation of miR-21 enhances chemotherapeutic effect of taxol in breast carcinoma cells. Technol Cancer Res Treat. 2010 Feb;9(1):77-86. doi: 10.1177/153303461000900109. | |
| 27696295 | Result | Yadav P, Mirza M, Nandi K, Jain SK, Kaza RC, Khurana N, Ray PC, Saxena A. Serum microRNA-21 expression as a prognostic and therapeutic biomarker for breast cancer patients. Tumour Biol. 2016 Nov;37(11):15275-15282. doi: 10.1007/s13277-016-5361-y. Epub 2016 Sep 30. |
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| ID | Term |
|---|---|
| D001943 | Breast Neoplasms |
| ID | Term |
|---|---|
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D001941 | Breast Diseases |
| D012871 | Skin Diseases |
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Blood sample
|
Relation between the miRNA 21 expression and the clinicopathological parameters |
| 1 year |
| 24172333 | Result | Ling H, Fabbri M, Calin GA. MicroRNAs and other non-coding RNAs as targets for anticancer drug development. Nat Rev Drug Discov. 2013 Nov;12(11):847-65. doi: 10.1038/nrd4140. |
| 16989803 | Result | Zhang B, Pan X, Cobb GP, Anderson TA. microRNAs as oncogenes and tumor suppressors. Dev Biol. 2007 Feb 1;302(1):1-12. doi: 10.1016/j.ydbio.2006.08.028. Epub 2006 Aug 16. |
| 26891730 | Result | Petrovic N. miR-21 Might be Involved in Breast Cancer Promotion and Invasion Rather than in Initial Events of Breast Cancer Development. Mol Diagn Ther. 2016 Apr;20(2):97-110. doi: 10.1007/s40291-016-0186-3. |
| 21219636 | Result | Yan LX, Wu QN, Zhang Y, Li YY, Liao DZ, Hou JH, Fu J, Zeng MS, Yun JP, Wu QL, Zeng YX, Shao JY. Knockdown of miR-21 in human breast cancer cell lines inhibits proliferation, in vitro migration and in vivo tumor growth. Breast Cancer Res. 2011 Jan 10;13(1):R2. doi: 10.1186/bcr2803. |
| 24606718 | Result | Chen L, Bourguignon LY. Hyaluronan-CD44 interaction promotes c-Jun signaling and miRNA21 expression leading to Bcl-2 expression and chemoresistance in breast cancer cells. Mol Cancer. 2014 Mar 8;13:52. doi: 10.1186/1476-4598-13-52. |
| 28683441 | Result | Schwarzenbach H. Clinical Relevance of Circulating, Cell-Free and Exosomal microRNAs in Plasma and Serum of Breast Cancer Patients. Oncol Res Treat. 2017;40(7-8):423-429. doi: 10.1159/000478019. Epub 2017 Jun 28. |
| 30099860 | Result | Zhu W, Liu M, Fan Y, Ma F, Xu N, Xu B. Dynamics of circulating microRNAs as a novel indicator of clinical response to neoadjuvant chemotherapy in breast cancer. Cancer Med. 2018 Sep;7(9):4420-4433. doi: 10.1002/cam4.1723. Epub 2018 Aug 11. |
| 22523546 | Result | Wang H, Tan G, Dong L, Cheng L, Li K, Wang Z, Luo H. Circulating MiR-125b as a marker predicting chemoresistance in breast cancer. PLoS One. 2012;7(4):e34210. doi: 10.1371/journal.pone.0034210. Epub 2012 Apr 16. |
| 28412211 | Result | Liu B, Su F, Chen M, Li Y, Qi X, Xiao J, Li X, Liu X, Liang W, Zhang Y, Zhang J. Serum miR-21 and miR-125b as markers predicting neoadjuvant chemotherapy response and prognosis in stage II/III breast cancer. Hum Pathol. 2017 Jun;64:44-52. doi: 10.1016/j.humpath.2017.03.016. Epub 2017 Apr 12. |
| D017437 |
| Skin and Connective Tissue Diseases |