Tissue and Serum MiRNA Profile in Locally Advanced Breast Cancer (LABC) in Response to Neo-Adjuvant Chemotherapy (NAC) Treatment

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2016 Apr 12

PMID 27064979

Citations 33

Authors

Manal Al-Khanbashi

Stefano Caramuta

Adil M Alajmi

Ibrahim Al-Haddabi

Marwa Al-Riyami

Weng-Onn Lui

Mansour S Al-Moundhri

Affiliations

Soon will be listed here.

Abstract

Introduction: MicroRNAs (miRNAs) are small non-coding RNA that plays a vital role in cancer progression. Neo-adjuvant chemotherapy (NAC) has become the standard of care for locally advanced breast cancer. The aim of this study was to evaluate miRNA alterations during NAC using multiple samples of tissue and serum to correlate miRNA expression with clinico-pathological features and patient outcomes.

Methods: Tissue and serum samples were collected from patients with locally advanced breast cancer undergoing NAC at four time points: time of diagnosis, after the first and fourth cycle of doxorubicin/cyclophosphamide treatment, and after the fourth cycle of docetaxel administration. First, we evaluated the miRNA expression profiles in tissue and correlated expression with clinico-pathological features. Then, a panel of four miRNAs (miR-451, miR-3200, miR-21, and miR-205) in serum samples was further validated using quantitative reverse-transcription polymerase chain reaction (RT-qPCR). The alterations in serum levels of miRNA, associations with clinical and pathological responses, correlation with clinico-pathological features, and survival outcomes were studied using Friedman, Mann-Whitney U, and Spearman, Wilcoxon signed-ranks tests. P≤0.05 was considered statistically significant.

Results: We analyzed 72 tissue samples and 108 serum samples from 9 patients and 27 patients, respectively. MicroRNA expression profiling of tumor versus normal tissue revealed more than 100 differentially expressed miRNAs. Serum miR-451 levels were significantly decreased during treatment, and higher serum levels were associated with improved clinical and pathological responses and disease-free survival. This is one of the early reports on miR-3200 in response to treatment in breast cancer, as serum levels of miR-3200 found to decline during NAC, and higher serum levels were associated with lower residual breast cancer burden and relapse rates at time of diagnosis.

Conclusion: Variations in serum miRNA levels during NAC treatment may be therapeutically significant for predicting response and survival outcomes.

Citing Articles

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References

Wickramasinghe N, Manavalan T, Dougherty S, Riggs K, Li Y, Klinge C . Estradiol downregulates miR-21 expression and increases miR-21 target gene expression in MCF-7 breast cancer cells. Nucleic Acids Res. 2009; 37(8):2584-95. PMC: 2677875. DOI: 10.1093/nar/gkp117. View

Wang F, Zheng Z, Guo J, Ding X . Correlation and quantitation of microRNA aberrant expression in tissues and sera from patients with breast tumor. Gynecol Oncol. 2010; 119(3):586-93. DOI: 10.1016/j.ygyno.2010.07.021. View

Yan L, Huang X, Shao Q, Huang M, Deng L, Wu Q . MicroRNA miR-21 overexpression in human breast cancer is associated with advanced clinical stage, lymph node metastasis and patient poor prognosis. RNA. 2008; 14(11):2348-60. PMC: 2578865. DOI: 10.1261/rna.1034808. View

Mattie M, Benz C, Bowers J, Sensinger K, Wong L, Scott G . Optimized high-throughput microRNA expression profiling provides novel biomarker assessment of clinical prostate and breast cancer biopsies. Mol Cancer. 2006; 5:24. PMC: 1563474. DOI: 10.1186/1476-4598-5-24. View

Nahleh Z, Sivasubramaniam D, Dhaliwal S, Sundarajan V, Komrokji R . Residual cancer burden in locally advanced breast cancer: a superior tool. Curr Oncol. 2008; 15(6):271-8. PMC: 2601022. DOI: 10.3747/co.v15i6.242. View

Wang G, Wang L, Sun S, Wu J, Wang Q . Quantitative measurement of serum microRNA-21 expression in relation to breast cancer metastasis in Chinese females. Ann Lab Med. 2015; 35(2):226-32. PMC: 4330173. DOI: 10.3343/alm.2015.35.2.226. View

Zhu W, Qin W, Atasoy U, Sauter E . Circulating microRNAs in breast cancer and healthy subjects. BMC Res Notes. 2009; 2:89. PMC: 2694820. DOI: 10.1186/1756-0500-2-89. View

van Schooneveld E, Wildiers H, Vergote I, Vermeulen P, Dirix L, Van Laere S . Dysregulation of microRNAs in breast cancer and their potential role as prognostic and predictive biomarkers in patient management. Breast Cancer Res. 2015; 17:21. PMC: 4332424. DOI: 10.1186/s13058-015-0526-y. View

Molnar V, Tamasi V, Bakos B, Wiener Z, Falus A . Changes in miRNA expression in solid tumors: an miRNA profiling in melanomas. Semin Cancer Biol. 2008; 18(2):111-22. DOI: 10.1016/j.semcancer.2008.01.001. View

10.

Iorio M, Ferracin M, Liu C, Veronese A, Spizzo R, Sabbioni S . MicroRNA gene expression deregulation in human breast cancer. Cancer Res. 2005; 65(16):7065-70. DOI: 10.1158/0008-5472.CAN-05-1783. View

11.

Xiong Y, Chen S, Liu L, Zhao Y, Lin W, Ni J . Increased serum microRNA-155 level associated with nonresponsiveness to hepatitis B vaccine. Clin Vaccine Immunol. 2013; 20(7):1089-91. PMC: 3697454. DOI: 10.1128/CVI.00044-13. View

12.

Burgos K, Javaherian A, Bomprezzi R, Ghaffari L, Rhodes S, Courtright A . Identification of extracellular miRNA in human cerebrospinal fluid by next-generation sequencing. RNA. 2013; 19(5):712-22. PMC: 3677285. DOI: 10.1261/rna.036863.112. View

13.

Khokher S, Qureshi M, Chaudhry N . Comparison of WHO and RECIST criteria for evaluation of clinical response to chemotherapy in patients with advanced breast cancer. Asian Pac J Cancer Prev. 2012; 13(7):3213-8. DOI: 10.7314/apjcp.2012.13.7.3213. View

14.

Heneghan H, Miller N, Lowery A, Sweeney K, Newell J, Kerin M . Circulating microRNAs as novel minimally invasive biomarkers for breast cancer. Ann Surg. 2010; 251(3):499-505. DOI: 10.1097/SLA.0b013e3181cc939f. View

15.

Majid S, Dar A, Saini S, Chen Y, Shahryari V, Liu J . Regulation of minichromosome maintenance gene family by microRNA-1296 and genistein in prostate cancer. Cancer Res. 2010; 70(7):2809-18. DOI: 10.1158/0008-5472.CAN-09-4176. View

16.

Hamfjord J, Stangeland A, Hughes T, Skrede M, Tveit K, Ikdahl T . Differential expression of miRNAs in colorectal cancer: comparison of paired tumor tissue and adjacent normal mucosa using high-throughput sequencing. PLoS One. 2012; 7(4):e34150. PMC: 3328481. DOI: 10.1371/journal.pone.0034150. View

17.

de Planell-Saguer M, Rodicio M . Detection methods for microRNAs in clinic practice. Clin Biochem. 2013; 46(10-11):869-78. DOI: 10.1016/j.clinbiochem.2013.02.017. View

18.

Calin G, Sevignani C, Dumitru C, Hyslop T, Noch E, Yendamuri S . Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers. Proc Natl Acad Sci U S A. 2004; 101(9):2999-3004. PMC: 365734. DOI: 10.1073/pnas.0307323101. View

19.

Kang W, Lee J, Oh S, Lee S, Jung C . Stromal expression of miR-21 in T3-4a colorectal cancer is an independent predictor of early tumor relapse. BMC Gastroenterol. 2015; 15:2. PMC: 4308857. DOI: 10.1186/s12876-015-0227-0. View

20.

Van der Auwera I, Limame R, van Dam P, Vermeulen P, Dirix L, Van Laere S . Integrated miRNA and mRNA expression profiling of the inflammatory breast cancer subtype. Br J Cancer. 2010; 103(4):532-41. PMC: 2939785. DOI: 10.1038/sj.bjc.6605787. View