Plasma miR-21, miR-155, miR-10b, and Let-7a as the potential biomarkers for the monitoring of breast cancer patients

There is a pressing need for further studies to categorize and validate circulating microRNAs (miRs) in breast cancer patients that can be one of the novel strategies for cancer screening and monitoring. The present study is aimed to investigate the expression of the circulating candidate microRNAs after the operation, chemotherapy, and radiotherapy in the non-metastatic breast cancer patients. Tumor tissue and plasma samples were collected from the 30 patients with recently diagnosed Luminal A breast cancer. Control plasma samples were collected from the 10 healthy subjects. A panel of four miRs including miR-21, miR-55, miR-10b, and Let-7a were selected and their expression levels were measured before and after the operation, chemotherapy, and radiotherapy by using Real-Time PCR technique. The plasma expression of the miR-21, miR-155, and miR-10b was significantly increased and the Let-7a plasma expression decreased in the breast cancer patients compromised to the control ones. There was a similar expression pattern of the miRs between the tissue and plasma samples. The plasma levels of the miR-21, miR-155, and miR-10b were significantly down-regulated and the Let-7a plasma level was up-regulated after the operation, chemotherapy, and radiotherapy compromised to the pre-treatment. There was a significant difference in the miR-155 plasma level after the operation, chemotherapy, and radiotherapy compromised with each other. Moreover, there was no significant difference between the plasma levels of the miRs after the radiotherapy compromised to the control cases. The operation, chemotherapy, and radiotherapy led to a more reduction in the oncomiRs and an increase in the tumor suppressor-miRs. It seems that monitoring miRs during treatment might be considered as a respectable diagnostic tool for monitoring of breast cancer patients.

[1]  Stefano Caramuta,et al.  Tissue and Serum miRNA Profile in Locally Advanced Breast Cancer (LABC) in Response to Neo-Adjuvant Chemotherapy (NAC) Treatment , 2016, PloS one.

[2]  Yang Li,et al.  HMDD v2.0: a database for experimentally supported human microRNA and disease associations , 2013, Nucleic Acids Res..

[3]  C. Croce,et al.  MicroRNAs in cancer: small molecules with a huge impact. , 2009, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[4]  A. Alizadeh,et al.  Expression of the circulating and the tissue microRNAs after surgery, chemotherapy, and radiotherapy in mice mammary tumor , 2016, Tumor Biology.

[5]  M. Hecker,et al.  Analysis of microRNA and Gene Expression Profiles in Multiple Sclerosis: Integrating Interaction Data to Uncover Regulatory Mechanisms , 2016, Scientific Reports.

[6]  C. Croce,et al.  MicroRNA dysregulation in cancer: diagnostics, monitoring and therapeutics. A comprehensive review , 2012, EMBO molecular medicine.

[7]  Alicia Algeciras-Schimnich,et al.  Analysis of circulating microRNA: preanalytical and analytical challenges. , 2011, Clinical chemistry.

[8]  Leonard D. Goldstein,et al.  MicroRNA expression profiling of human breast cancer identifies new markers of tumor subtype , 2007, Genome Biology.

[9]  D. Pang,et al.  A novel panel of serum miR-21/miR-155/miR-365 as a potential diagnostic biomarker for breast cancer , 2017, Annals of surgical treatment and research.

[10]  F. Slack,et al.  OncomiR or Tumor Suppressor? The Duplicity of MicroRNAs in Cancer. , 2016, Cancer research.

[11]  Susumu Goto,et al.  KEGG: Kyoto Encyclopedia of Genes and Genomes , 2000, Nucleic Acids Res..

[12]  G. Calin,et al.  Prognostic value of miR-155 in individuals with monoclonal B-cell lymphocytosis and patients with B chronic lymphocytic leukemia. , 2013, Blood.

[13]  Yu Sun,et al.  Serum MicroRNA-155 as a Potential Biomarker to Track Disease in Breast Cancer , 2012, PloS one.

[14]  S. Nam,et al.  The Clinicopathological Significance of MicroRNA-155 in Breast Cancer: A Meta-Analysis , 2014, BioMed research international.

[15]  K. J. Sweeney,et al.  MicroRNAs as Novel Biomarkers for Breast Cancer , 2009, Journal of oncology.

[16]  Hsiao-Fang Sunny Sun,et al.  In silico identification of oncogenic potential of fyn-related kinase in hepatocellular carcinoma , 2013, Bioinform..

[17]  R. Shiekhattar,et al.  MicroRNA biogenesis and cancer. , 2005, Cancer research.

[18]  M. Kassem,et al.  Circulating microRNAs in breast cancer: novel diagnostic and prognostic biomarkers , 2017, Cell Death & Disease.

[19]  A. Alizadeh,et al.  Effects of exercise training together with tamoxifen in reducing mammary tumor burden in mice: Possible underlying pathway of miR-21. , 2015, European journal of pharmacology.

[20]  Eduardo Andrés-León,et al.  Tumor microRNA expression profiling identifies circulating microRNAs for early breast cancer detection. , 2015, Clinical chemistry.

[21]  Wei Zhang,et al.  MicroRNA regulation of integrins. , 2013, Translational research : the journal of laboratory and clinical medicine.

[22]  Sean R. Davis,et al.  NCBI GEO: archive for functional genomics data sets—update , 2012, Nucleic Acids Res..

[23]  X. Chen,et al.  Characterization of microRNAs in serum: a novel class of biomarkers for diagnosis of cancer and other diseases , 2008, Cell Research.

[24]  Xiaohe Yang,et al.  microRNA Regulation in Estrogen Receptor-Positive Breast Cancer and Endocrine Therapy , 2018, Biological Procedures Online.

[25]  Imran Babar,et al.  MicroRNAs as potential agents to alter resistance to cytotoxic anticancer therapy. , 2007, Cancer research.

[26]  Michael Kertesz,et al.  The role of site accessibility in microRNA target recognition , 2007, Nature Genetics.

[27]  M. Bushell,et al.  microRNAs in cancer management. , 2012, The Lancet. Oncology.

[28]  K. Gunsalus,et al.  Combinatorial microRNA target predictions , 2005, Nature Genetics.

[29]  Hua Zhao,et al.  A Pilot Study of Circulating miRNAs as Potential Biomarkers of Early Stage Breast Cancer , 2010, PloS one.

[30]  Zhonghu Bai,et al.  Breast cancer intrinsic subtype classification, clinical use and future trends. , 2015, American journal of cancer research.

[31]  E. Kistner,et al.  Let-7 expression defines two differentiation stages of cancer , 2007, Proceedings of the National Academy of Sciences.

[32]  S. Lawler,et al.  MicroRNAs in cancer: biomarkers, functions and therapy. , 2014, Trends in molecular medicine.

[33]  R. S. Huang,et al.  Identification of MicroRNAs as Breast Cancer Prognosis Markers through the Cancer Genome Atlas , 2016, PloS one.

[34]  F. Badr Potential Role of miR-21 in Breast Cancer Diagnosis and Therapy , 2016 .

[35]  A. Ahmadi,et al.  New insight to IL-23/IL-17 axis in Iranian infected adult patients with gastritis: effects of genes polymorphisms on expression of cytokines. , 2015, Acta gastro-enterologica Belgica.

[36]  T. Stopka,et al.  Oncogenic MicroRNAs: miR-155, miR-19a, miR-181b, and miR-24 enable monitoring of early breast cancer in serum , 2014, BMC Cancer.

[37]  L. Sempere,et al.  Critical analysis of the potential for microRNA biomarkers in breast cancer management , 2015, Breast cancer.

[38]  Qian Song,et al.  MicroRNA-10b and the clinical outcomes of various cancers: A systematic review and meta-analysis. , 2017, Clinica chimica acta; international journal of clinical chemistry.

[39]  Lin Zhang,et al.  Double-negative feedback loop between reprogramming factor LIN28 and microRNA let-7 regulates aldehyde dehydrogenase 1-positive cancer stem cells. , 2010, Cancer research.

[40]  International criteria for measurement of tumour response , 2001, Cancer Imaging.

[41]  M. Daidone,et al.  Circulating Biomarkers for Prediction of Treatment Response. , 2015, Journal of the National Cancer Institute. Monographs.

[42]  Anton J. Enright,et al.  MicroRNA targets in Drosophila , 2003, Genome Biology.

[43]  Hiroyuki Ogata,et al.  KEGG: Kyoto Encyclopedia of Genes and Genomes , 1999, Nucleic Acids Res..

[44]  Xiaowei Wang,et al.  Sequence analysis Prediction of both conserved and nonconserved microRNA targets in animals , 2007 .

[45]  Carme Camps,et al.  MicroRNA-10b and breast cancer metastasis , 2008, Nature.

[46]  A. Alizadeh,et al.  MicroRNA-206, let-7a and microRNA-21 pathways involved in the anti-angiogenesis effects of the interval exercise training and hormone therapy in breast cancer. , 2016, Life sciences.

[47]  Ulus Atasoy,et al.  Circulating microRNAs in breast cancer and healthy subjects , 2009, BMC Research Notes.

[48]  R. Weinberg,et al.  Tumour invasion and metastasis initiated by microRNA-10b in breast cancer , 2007, Nature.

[49]  Alexander Stojadinovic,et al.  Current Approaches and Challenges in Monitoring Treatment Responses in Breast Cancer , 2014, Journal of Cancer.

[50]  Zhongming Zhao,et al.  TSGene: a web resource for tumor suppressor genes , 2012, Nucleic Acids Res..

[51]  Thomas D. Schmittgen,et al.  Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. , 2001, Methods.