Skip to main content
Erschienen in: Tumor Biology 11/2016

30.09.2016 | Original Article

Serum microRNA-21 expression as a prognostic and therapeutic biomarker for breast cancer patients

verfasst von: Prasant Yadav, Masroor Mirza, Kajal Nandi, S. K. Jain, R. C. M. Kaza, Nita Khurana, P. C. Ray, Alpana Saxena

Erschienen in: Tumor Biology | Ausgabe 11/2016

Einloggen, um Zugang zu erhalten

Abstract

MiRNA-21 is recognized as the main active candidate and high expression in many solid tumors consequential cell proliferation, differentiation, apoptosis, and closely related to metastasis of disease. The study aimed to evaluate the serum miRNA-21 expression and therapy outcome in breast cancer patients and cell lines. Seventy-five histopathologically confirmed newly diagnosed breast cancer patients were included in the study; before and after therapy, patient’s blood sample were collected and analyzed for serum microRNA-21 expression by quantitative real-time PCR. In patients, 8.9 mean fold increased microRNA-21 expression was observed compared to controls. Increased expression was found to be associated with advanced stage (11.72-fold), lymph node involvement (11.12-fold), and distant metastases (20.17-fold). After treatment significant decrease in miRNA-21 expression was observed and found to be significant (p < 0.0001). Patients treated with neoadjuvant therapy had significant impact on miRNA-21 suppression and found to be significantly associated with different clinicopathological features of patients. Increased miRNA-21 expression was also found to be significantly associated with poor survival of breast cancer patients (p = 0.002). MicroRNA-21 expression could be used as promising predictive indicators for breast cancer prognosis. MicroRNA-21 over-expression was associated with response to neoadjuvant therapy and may perhaps be considered as primary treatment choice.
Literatur
2.
Zurück zum Zitat Mitchell PS, Parkin RK, Kroh EM, Fritz BR, Wyman SK, Pogosova-Agadjanyan EL, et al. Circulating microRNAs as stable blood-based markers for cancer detection. Proc Natl Acad Sci U S A. 2008;105:10513–8.CrossRefPubMedPubMedCentral Mitchell PS, Parkin RK, Kroh EM, Fritz BR, Wyman SK, Pogosova-Agadjanyan EL, et al. Circulating microRNAs as stable blood-based markers for cancer detection. Proc Natl Acad Sci U S A. 2008;105:10513–8.CrossRefPubMedPubMedCentral
3.
Zurück zum Zitat Meng F, Henson R, Wehbe-Janek H, Ghoshal K, Jacob ST, Patel T. MicroRNA- 21 regulates expression of the PTEN tumor suppressor gene in human hepatocellular cancer. Gastroenterology. 2007;133:647–58.CrossRefPubMedPubMedCentral Meng F, Henson R, Wehbe-Janek H, Ghoshal K, Jacob ST, Patel T. MicroRNA- 21 regulates expression of the PTEN tumor suppressor gene in human hepatocellular cancer. Gastroenterology. 2007;133:647–58.CrossRefPubMedPubMedCentral
4.
Zurück zum Zitat Asangani IA, Rasheed SA, Nikolova DA, Leupold JH, Colburn NH, Post S, et al. MicroRNA-21 (miR-21) post-transcriptionally downregulates tumor suppressor Pdcd4 and stimulates invasion, intravasation and metastasis in colorectal cancer. Oncogene. 2008;27:2128–36.CrossRefPubMed Asangani IA, Rasheed SA, Nikolova DA, Leupold JH, Colburn NH, Post S, et al. MicroRNA-21 (miR-21) post-transcriptionally downregulates tumor suppressor Pdcd4 and stimulates invasion, intravasation and metastasis in colorectal cancer. Oncogene. 2008;27:2128–36.CrossRefPubMed
5.
Zurück zum Zitat Papagiannakopoulos T, Shapiro A, Kosik KS. MicroRNA-21 targets a network of key tumor-suppressive pathways in glioblastoma cells. Cancer Res. 2008;68:8164–72.CrossRefPubMed Papagiannakopoulos T, Shapiro A, Kosik KS. MicroRNA-21 targets a network of key tumor-suppressive pathways in glioblastoma cells. Cancer Res. 2008;68:8164–72.CrossRefPubMed
6.
Zurück zum Zitat Iorio MV, Ferracin M, Liu CG, Veronese A, Spizzo R, Sabbioni S, et al. MicroRNA gene expression deregulation in human breast cancer. Cancer Res. 2005;65:7065–70.CrossRefPubMed Iorio MV, Ferracin M, Liu CG, Veronese A, Spizzo R, Sabbioni S, et al. MicroRNA gene expression deregulation in human breast cancer. Cancer Res. 2005;65:7065–70.CrossRefPubMed
7.
Zurück zum Zitat Luo X, Burwinkel B, Tao S, Brenner H. MicroRNA signatures: novel biomarker for colorectal cancer? Cancer Epidemiol Biomarkers Prev. 2011;20(7):1272–86.CrossRefPubMed Luo X, Burwinkel B, Tao S, Brenner H. MicroRNA signatures: novel biomarker for colorectal cancer? Cancer Epidemiol Biomarkers Prev. 2011;20(7):1272–86.CrossRefPubMed
8.
Zurück zum Zitat Skrzypski M, Dziadziuszko R, Jassem J. MicroRNA in lung cancer diagnostics and treatment. Mutat Res. 2011;717(1–2):25–31.CrossRefPubMed Skrzypski M, Dziadziuszko R, Jassem J. MicroRNA in lung cancer diagnostics and treatment. Mutat Res. 2011;717(1–2):25–31.CrossRefPubMed
9.
Zurück zum Zitat Zhao L, Chen X, Cao Y. New role of microRNA: carcinogenesis and clinical application in cancer. Acta Biochim Biophys Sin Shanghai. 2011;43(11):831–9.CrossRefPubMed Zhao L, Chen X, Cao Y. New role of microRNA: carcinogenesis and clinical application in cancer. Acta Biochim Biophys Sin Shanghai. 2011;43(11):831–9.CrossRefPubMed
10.
Zurück zum Zitat Moore LM, Zhang W. Targeting miR-21 in glioma: a small RNA with big potential. Expert Opin Ther Targets. 2010;14(11):1247–57.CrossRefPubMed Moore LM, Zhang W. Targeting miR-21 in glioma: a small RNA with big potential. Expert Opin Ther Targets. 2010;14(11):1247–57.CrossRefPubMed
11.
Zurück zum Zitat Selcuklu SD, Donoghue MT, Spillane C. miR-21 as a key regulator of oncogenic processes. Biochem Soc Trans. 2009;37(Pt 4):918–25.CrossRefPubMed Selcuklu SD, Donoghue MT, Spillane C. miR-21 as a key regulator of oncogenic processes. Biochem Soc Trans. 2009;37(Pt 4):918–25.CrossRefPubMed
12.
Zurück zum Zitat Krichevsky AM, Gabriely G. miR-21: a small multi-faceted RNA. J Cell Mol Med. 2009;13(1):39–53.CrossRefPubMed Krichevsky AM, Gabriely G. miR-21: a small multi-faceted RNA. J Cell Mol Med. 2009;13(1):39–53.CrossRefPubMed
13.
Zurück zum Zitat Rossi S, Shimizu M, Barbarotto E, Nicoloso MS, Dimitri F, Sampath D, et al. microRNA fingerprinting of CLL patients with chromosome 17p deletion identify a miR-21 score that stratifies early survival. Blood. 2010;116(6):945–52.CrossRefPubMedPubMedCentral Rossi S, Shimizu M, Barbarotto E, Nicoloso MS, Dimitri F, Sampath D, et al. microRNA fingerprinting of CLL patients with chromosome 17p deletion identify a miR-21 score that stratifies early survival. Blood. 2010;116(6):945–52.CrossRefPubMedPubMedCentral
14.
15.
Zurück zum Zitat Corcoran C, Friel AM, Duffy MJ, Crown J, O’Driscoll L. Intracellular and extracellular microRNAs in breast cancer. Clin Chem. 2011;57:18–32.CrossRefPubMed Corcoran C, Friel AM, Duffy MJ, Crown J, O’Driscoll L. Intracellular and extracellular microRNAs in breast cancer. Clin Chem. 2011;57:18–32.CrossRefPubMed
16.
Zurück zum Zitat Mei M, Ren Y, Zhou X, Yuan XB, Han L, Wang GX, et al. Downregulation of miR-21 enhances chemotherapeutic effect of taxol in breast carcinoma cells. Technol Cancer Res Treat. 2010;9:77–86.CrossRefPubMed Mei M, Ren Y, Zhou X, Yuan XB, Han L, Wang GX, et al. Downregulation of miR-21 enhances chemotherapeutic effect of taxol in breast carcinoma cells. Technol Cancer Res Treat. 2010;9:77–86.CrossRefPubMed
17.
Zurück zum Zitat 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;13:52.CrossRefPubMedPubMedCentral 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;13:52.CrossRefPubMedPubMedCentral
18.
Zurück zum Zitat Dong J, Zhao YP, Zhou L, Zhang TP, Chen G. Bcl-2 upregulation induced by miR-21 via a direct interaction is associated with apoptosis and chemoresistance in MIA PaCa-2 pancreatic cancer cells. Arch Med Res. 2011;42:8–14.CrossRefPubMed Dong J, Zhao YP, Zhou L, Zhang TP, Chen G. Bcl-2 upregulation induced by miR-21 via a direct interaction is associated with apoptosis and chemoresistance in MIA PaCa-2 pancreatic cancer cells. Arch Med Res. 2011;42:8–14.CrossRefPubMed
21.
Zurück zum Zitat Mishra PJ, Merlino G. MicroRNA reexpression as differentiation therapy in cancer. J Clin Invest. 2009;119:2119–23.PubMedPubMedCentral Mishra PJ, Merlino G. MicroRNA reexpression as differentiation therapy in cancer. J Clin Invest. 2009;119:2119–23.PubMedPubMedCentral
22.
Zurück zum Zitat Chen X, Ba Y, Ma L, et al. Characterization of microRNAs in serum: a novel class of biomarkers for diagnosis of cancer and other diseases. Cell Res. 2008;18:997–1006.CrossRefPubMed Chen X, Ba Y, Ma L, et al. Characterization of microRNAs in serum: a novel class of biomarkers for diagnosis of cancer and other diseases. Cell Res. 2008;18:997–1006.CrossRefPubMed
23.
Zurück zum Zitat Asaga S, Kuo C, Nguyen T, Terpenning M, Giuliano AE, Hoon DS. Direct serum assay for microRNA-21 concentrations in early and advanced breast cancer. Clin Chem. 2011;57:84–91.CrossRefPubMed Asaga S, Kuo C, Nguyen T, Terpenning M, Giuliano AE, Hoon DS. Direct serum assay for microRNA-21 concentrations in early and advanced breast cancer. Clin Chem. 2011;57:84–91.CrossRefPubMed
24.
Zurück zum Zitat Wang ZX, Bian HB, Wang JR, Cheng ZX, Wang KM, De W. Prognostic significance of serum miRNA-21 expression in human non-small cell lung cancer. J Surg Oncol. 2011;104:847–51.CrossRefPubMed Wang ZX, Bian HB, Wang JR, Cheng ZX, Wang KM, De W. Prognostic significance of serum miRNA-21 expression in human non-small cell lung cancer. J Surg Oncol. 2011;104:847–51.CrossRefPubMed
25.
Zurück zum Zitat Si H, Sun X, Chen Y, Cao Y, Chen S, Wang H, et al. Circulating microRNA-92a and microRNA-21 as novel minimally invasive biomarkers for primary breast cancer. J Cancer Res Clin Oncol. 2013;139(2):223–9.CrossRefPubMed Si H, Sun X, Chen Y, Cao Y, Chen S, Wang H, et al. Circulating microRNA-92a and microRNA-21 as novel minimally invasive biomarkers for primary breast cancer. J Cancer Res Clin Oncol. 2013;139(2):223–9.CrossRefPubMed
26.
Zurück zum Zitat Ng EK, Li R, Shin VY, Jin HC, Leung CP, Ma ES, et al. Circulating microRNAs as specific biomarkers for breast cancer detection. PLoS One. 2013;8(1), e53141.CrossRefPubMedPubMedCentral Ng EK, Li R, Shin VY, Jin HC, Leung CP, Ma ES, et al. Circulating microRNAs as specific biomarkers for breast cancer detection. PLoS One. 2013;8(1), e53141.CrossRefPubMedPubMedCentral
27.
Zurück zum Zitat Sempere LF, Kauppinen S. In: Bradshaw RA, Dennis EA, editors. Translational implications of microRNAs in clinical diagnostics and therapeutics: handbook of cell signaling. Oxford: Academic; 2009. p. 2965–e2981. Sempere LF, Kauppinen S. In: Bradshaw RA, Dennis EA, editors. Translational implications of microRNAs in clinical diagnostics and therapeutics: handbook of cell signaling. Oxford: Academic; 2009. p. 2965–e2981.
28.
Zurück zum Zitat Schwartz GF, Hortobagyi GN, Masood S, Palazzo J, Holland R, Page D. Proceedings of the consensus conference on neoadjuvant chemotherapy in carcinoma of the breast, April 26–28, 2003, Philadelphia, PA. Hum Pathol. 2004;35:781–4.CrossRefPubMed Schwartz GF, Hortobagyi GN, Masood S, Palazzo J, Holland R, Page D. Proceedings of the consensus conference on neoadjuvant chemotherapy in carcinoma of the breast, April 26–28, 2003, Philadelphia, PA. Hum Pathol. 2004;35:781–4.CrossRefPubMed
29.
Zurück zum Zitat Kaufmann M, von Minckwitz G, Bear HD, Buzdar A, McGale P, Bonnefoi H, et al. Recommendations from an international expert panel on the use of neoadjuvant (primary) systemic treatment of operable breast cancer: new perspectives 2006. Ann Oncol. 2007;18:1927–34.CrossRefPubMed Kaufmann M, von Minckwitz G, Bear HD, Buzdar A, McGale P, Bonnefoi H, et al. Recommendations from an international expert panel on the use of neoadjuvant (primary) systemic treatment of operable breast cancer: new perspectives 2006. Ann Oncol. 2007;18:1927–34.CrossRefPubMed
30.
Zurück zum Zitat Chia S, Swain SM, Byrd DR, Mankoff DA. Locally advanced and inflammatory breast cancer. J Clin Oncol. 2008;26:786–90.CrossRefPubMed Chia S, Swain SM, Byrd DR, Mankoff DA. Locally advanced and inflammatory breast cancer. J Clin Oncol. 2008;26:786–90.CrossRefPubMed
Metadaten
Titel
Serum microRNA-21 expression as a prognostic and therapeutic biomarker for breast cancer patients
verfasst von
Prasant Yadav
Masroor Mirza
Kajal Nandi
S. K. Jain
R. C. M. Kaza
Nita Khurana
P. C. Ray
Alpana Saxena
Publikationsdatum
30.09.2016
Verlag
Springer Netherlands
Erschienen in
Tumor Biology / Ausgabe 11/2016
Print ISSN: 1010-4283
Elektronische ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-016-5361-y

Weitere Artikel der Ausgabe 11/2016

Tumor Biology 11/2016 Zur Ausgabe

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.