Five MicroRNAs in Serum Are Able to Differentiate Breast Cancer Patients From Healthy Individuals

Overview

Journal Front Oncol

Specialty Oncology

Date 2020 Nov 23

PMID 33224883

Citations 10

Authors

Andrea Feliciano

Lucila Gonzalez

Yoelsis Garcia-Mayea

Cristina Mir

Mireia Artola

Nieves Barragan

Remedios Martin

Anna Altes

Josep Castellvi

Sergi Benavente

Santiago Ramon Y Cajal

Martin Espinosa-Bravo

Javier Cortes

Isabel T Rubio

Matilde E LLeonart

Affiliations

Soon will be listed here.

Abstract

Breast cancer is the cancer with the most incidence and mortality in women. microRNAs are emerging as novel prognosis/diagnostic tools. Our aim was to identify a serum microRNA signature useful to predict cancer development. We focused on studying the expression levels of 30 microRNAs in the serum of 96 breast cancer patients . 92 control individuals. Bioinformatic studies provide a microRNA signature, designated as a predictor, based on the expression levels of five microRNAs. Then, we tested the predictor in a group of 60 randomly chosen women. Lastly, a proteomic study unveiled the overexpression and downregulation of proteins differently expressed in the serum of breast cancer patients . that of control individuals. Twenty-six microRNAs differentiate cancer tissue from healthy tissue, and 16 microRNAs differentiate the serum of cancer patients from that of the control group. The tissue expression of miR-99a, miR-497, miR-362, and miR-1274, and the serum levels of miR-141 correlated with patient survival. Moreover, the predictor consisting of miR-125b, miR-29c, miR-16, miR-1260, and miR-451 was able to differentiate breast cancer patients from controls. The predictor was validated in 20 new cases of breast cancer patients and tested in 60 volunteer women, assigning 11 out of 60 women to the cancer group. An association of low levels of miR-16 with a high content of CD44 protein in serum was found. Circulating microRNAs in serum can represent biomarkers for cancer prediction. Their clinical relevance and the potential use of the predictor here described are discussed.

Citing Articles

Dysregulation of MiR-21, MiR-221 and MiR-451 During Neoadjuvant Treatment of Breast Cancer: A Prospective Study.

Patury C, Santos B, Matos A, Slabi J, Gastalho L, Kaneto C Biomolecules. 2025; 14(12.

PMID: 39766287 PMC: 11674781. DOI: 10.3390/biom14121580.

Circulating Micro-RNAs Predict the Risk of Recurrence in Triple-Negative Breast Cancer.

Kujala J, Tengstrom M, Heikkinen S, Taipale M, Kosma V, Hartikainen J Cells. 2024; 13(22).

PMID: 39594632 PMC: 11593277. DOI: 10.3390/cells13221884.

The role of miRNAs as biomarkers in breast cancer.

Baylie T, Kasaw M, Getinet M, Getie G, Jemal M, Nigatu A Front Oncol. 2024; 14:1374821.

PMID: 38812786 PMC: 11133523. DOI: 10.3389/fonc.2024.1374821.

Applying Machine Learning for Enhanced MicroRNA Analysis: A Companion Risk Tool for Oral Squamous Cell Carcinoma in Standard Care Incisional Biopsy.

Pruthi N, Yap T, Moore C, Cirillo N, McCullough M Biomolecules. 2024; 14(4).

PMID: 38672474 PMC: 11048287. DOI: 10.3390/biom14040458.

Breast cancer tumor microenvironment affects Treg/IL-17-producing Treg/Th17 cell axis: Molecular and therapeutic perspectives.

Seif F, Torki Z, Zalpoor H, Habibi M, Pornour M Mol Ther Oncolytics. 2023; 28:132-157.

PMID: 36816749 PMC: 9922830. DOI: 10.1016/j.omto.2023.01.001.

References

Huang G, Sun J, Lu Y, Liu Y, Cao H, Zhang H . MiR-200 family and cancer: From a meta-analysis view. Mol Aspects Med. 2019; 70:57-71. DOI: 10.1016/j.mam.2019.09.005. View

Rodriguez-Martinez A, de Miguel-Perez D, Ortega F, Garcia-Puche J, Robles-Fernandez I, Exposito J . Exosomal miRNA profile as complementary tool in the diagnostic and prediction of treatment response in localized breast cancer under neoadjuvant chemotherapy. Breast Cancer Res. 2019; 21(1):21. PMC: 6366103. DOI: 10.1186/s13058-019-1109-0. View

Ru Y, Kechris K, Tabakoff B, Hoffman P, Radcliffe R, Bowler R . The multiMiR R package and database: integration of microRNA-target interactions along with their disease and drug associations. Nucleic Acids Res. 2014; 42(17):e133. PMC: 4176155. DOI: 10.1093/nar/gku631. View

Wang H, Tan G, Dong L, Cheng L, Li K, Wang Z . Circulating MiR-125b as a marker predicting chemoresistance in breast cancer. PLoS One. 2012; 7(4):e34210. PMC: 3327688. DOI: 10.1371/journal.pone.0034210. View

Sochor M, Basova P, Pesta M, Dusilkova N, Bartos J, Burda P . Oncogenic microRNAs: miR-155, miR-19a, miR-181b, and miR-24 enable monitoring of early breast cancer in serum. BMC Cancer. 2014; 14:448. PMC: 4075993. DOI: 10.1186/1471-2407-14-448. View

Madhavan D, Peng C, Wallwiener M, Zucknick M, Nees J, Schott S . Circulating miRNAs with prognostic value in metastatic breast cancer and for early detection of metastasis. Carcinogenesis. 2016; 37(5):461-70. DOI: 10.1093/carcin/bgw008. View

Pendharkar N, Dhali S, Abhang S . A Novel Strategy to Investigate Tissue-Secreted Tumor Microenvironmental Proteins in Serum toward Development of Breast Cancer Early Diagnosis Biomarker Signature. Proteomics Clin Appl. 2018; 13(3):e1700119. DOI: 10.1002/prca.201700119. View

Matamala N, Vargas M, Gonzalez-Campora R, Minambres R, Arias J, Menendez P . Tumor microRNA expression profiling identifies circulating microRNAs for early breast cancer detection. Clin Chem. 2015; 61(8):1098-106. DOI: 10.1373/clinchem.2015.238691. View

Debeb B, Lacerda L, Anfossi S, Diagaradjane P, Chu K, Bambhroliya A . miR-141-Mediated Regulation of Brain Metastasis From Breast Cancer. J Natl Cancer Inst. 2016; 108(8). PMC: 5017951. DOI: 10.1093/jnci/djw026. View

10.

Tumminello F, Flandina C, Crescimanno M, Leto G . Circulating cathepsin K and cystatin C in patients with cancer related bone disease: clinical and therapeutic implications. Biomed Pharmacother. 2007; 62(2):130-5. DOI: 10.1016/j.biopha.2007.07.001. View

11.

Zaleski M, Kobilay M, Schroeder L, Debald M, Semaan A, Hettwer K . Improved sensitivity for detection of breast cancer by combination of miR-34a and tumor markers CA 15-3 or CEA. Oncotarget. 2018; 9(32):22523-22536. PMC: 5976482. DOI: 10.18632/oncotarget.25077. View

12.

Bonjoch L, Casas V, Carrascal M, Closa D . Involvement of exosomes in lung inflammation associated with experimental acute pancreatitis. J Pathol. 2016; 240(2):235-45. DOI: 10.1002/path.4771. View

13.

Guillen-Gomez E, Bardaji-de-Quixano B, Ferrer S, Brotons C, Knepper M, Carrascal M . Urinary Proteome Analysis Identified Neprilysin and VCAM as Proteins Involved in Diabetic Nephropathy. J Diabetes Res. 2018; 2018:6165303. PMC: 5949160. DOI: 10.1155/2018/6165303. View

14.

Xiang M, Zeng Y, Yang R, Xu H, Chen Z, Zhong J . U6 is not a suitable endogenous control for the quantification of circulating microRNAs. Biochem Biophys Res Commun. 2014; 454(1):210-4. DOI: 10.1016/j.bbrc.2014.10.064. View

15.

Vasconcelos I, Hussainzada A, Berger S, Fietze E, Linke J, Siedentopf F . The St. Gallen surrogate classification for breast cancer subtypes successfully predicts tumor presenting features, nodal involvement, recurrence patterns and disease free survival. Breast. 2016; 29:181-5. DOI: 10.1016/j.breast.2016.07.016. View

16.

Chen C, Zhao S, Karnad A, Freeman J . The biology and role of CD44 in cancer progression: therapeutic implications. J Hematol Oncol. 2018; 11(1):64. PMC: 5946470. DOI: 10.1186/s13045-018-0605-5. View

17.

DeSantis C, Ma J, Sauer A, Newman L, Jemal A . Breast cancer statistics, 2017, racial disparity in mortality by state. CA Cancer J Clin. 2017; 67(6):439-448. DOI: 10.3322/caac.21412. View

18.

Yu X, Liang J, Xu J, Li X, Xing S, Li H . Identification and Validation of Circulating MicroRNA Signatures for Breast Cancer Early Detection Based on Large Scale Tissue-Derived Data. J Breast Cancer. 2019; 21(4):363-370. PMC: 6310725. DOI: 10.4048/jbc.2018.21.e56. View

19.

Madhavan D, Cuk K, Burwinkel B, Yang R . Cancer diagnosis and prognosis decoded by blood-based circulating microRNA signatures. Front Genet. 2013; 4:116. PMC: 3689027. DOI: 10.3389/fgene.2013.00116. View

20.

Kong Y, Lyu N, Wu J, Tang H, Xie X, Yang L . Breast cancer stem cell markers CD44 and ALDH1A1 in serum: distribution and prognostic value in patients with primary breast cancer. J Cancer. 2018; 9(20):3728-3735. PMC: 6215997. DOI: 10.7150/jca.28032. View