Evaluation of the Sensitivity and Specificity of Circulating MicroRNAs to Diagnose Breast Cancer: A Systematic Review and Meta-analysis

Document Type : Review Article

Authors

1 School of Medicine, Capital Medical University, Beijing, China

2 Department of General Surgery, Fudan University Affiliated Huadong Hospital, Shanghai 200040, China

3 Medical Center of Digestive Disease, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China

4 Department of Obstetrics and Gynecology, The second Affiliated Hospital of Soochow University, Suzhou, China

Abstract

Background and aim: Today, scientists use cell-free circulating microRNAs (miRNAs) biomarkers to identify, control, and treat cancer, even in its early stages. The present study aimed to evaluate the sensitivity and specificity of circulating microRNAs to diagnose breast cancer.
Material and methods: The search was conducted based on keywords related to the study objectives in the international databases PubMed, Scopus, Science Direct, ISI, Web of Knowledge, and Embase between January 2015 and March 2023. Effect size (95% confidence interval) was calculated using the fixed effect model with the inverse-variance method. STATA/MP. V17 software was used for meta-analysis.
Results: In the present study, 31 articles were included in the meta-analysis. Sensitivity of circulating microRNAs to diagnose breast cancer was 85% (ES: 0.85 [95% CI: 0.74, 0.95]. Specificity of circulating microRNAs to diagnose breast cancer was 85% (ES: 0.85 [95% CI: 0.75, 0.96]. The AUC of miR-21 to diagnose breast cancer was 84% (ES: 0.84 [95% CI: 0.71, 0.97].
Conclusions: Based on the present meta-analysis, circulating microRNAs are promising biomarkers in breast cancer diagnosis.

Keywords

Main Subjects


[1]  Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. Ca Cancer J Clin. 2018;68(6):394-424.
[2]  El Sharif N, Khatib I. Healthy Lifestyle and Breast Cancer Risk in Palestinian Women: A Case-Control Study. Nutrition and Cancer. 2023:1-1. https://doi.org/10.1080/01635581.2023.2168022.
[3]  Yuniastini Y, Murhan A, Purwati P, Pratiwi MD. Risk Factors for Breast Cancer: Hormonal Contraception. Jurnal Aisyah: Jurnal Ilmu Kesehatan. 2022;7(S1):349-54. http://dx.doi.org/10.30604/jika.v7iS1.1307.
[4]  Singh R, kumar Sain MN. Etiology Of Breast Cancer. Journal of Pharmaceutical Negative Results. 2023:1427-34. https://doi.org/10.47750/pnr.2023.14.03.192.
[5]  Ho AY, Barker CA, Arnold BB, Powell SN, Hu ZI, Gucalp Aet al. A phase 2 clinical trial assessing the efficacy and safety of pembrolizumab and radiotherapy in patients with metastatic triple‐negative breast cancer. Cancer. 2020;126(4):850-60. https://doi.org/10.1002/cncr.32599.
[6]  Pashayan N, Antoniou AC, Ivanus U, Esserman LJ, Easton DF, French D, et al. Personalized early detection and prevention of breast cancer: ENVISION consensus statement. Nature Reviews Clinical Oncology. 2020;17(11):687-705. https://doi.org/10.1038/s41571-020-0388-9.
[7]  Cai X, Li X, Razmjooy N, Ghadimi N. Breast cancer diagnosis by convolutional neural network and advanced thermal exchange optimization algorithm. Computational and Mathematical Methods in Medicine. 2021. https://doi.org/10.1155/2021/5595180.
[8]  Balali GI. Breast cancer: a review of mammography and clinical breast examination for early detection of cancer. Open Access Library Journal. 2020;7(10):1. https://doi.org/10.4236/oalib.1106866.
[9]  Heindel W, Weigel S, Gerß J, Hense HW, Sommer A, Krischke M, et al. Digital breast tomosynthesis plus synthesised mammography versus digital screening mammography for the detection of invasive breast cancer (TOSYMA): a multicentre, open-label, randomised, controlled, superiority trial. The Lancet Oncology. 2022;23(5):601-11. https://doi.org/10.1016/S1470-2045(22)00194-2.
[10] Iranmakani S, Mortezazadeh T, Sajadian F, Ghaziani MF, Ghafari A, Khezerloo D, et al. A review of various modalities in breast imaging: technical aspects and clinical outcomes. Egyptian Journal of Radiology and Nuclear Medicine. 2020;51(1):1-22. https://doi.org/10.1186/s43055-020-00175-5.
[11] Smith RA, Andrews KS, Brooks D, Fedewa SA, Manassaram-Baptiste D, Saslow D, et al. Cancer screening in the United States, 2019: A review of current American Cancer Society guidelines and current issues in cancer screening. CA: a cancer journal for clinicians. 2019;69(3):184-210. https://doi.org/10.3322/caac.21557.
[12] Jusoh AR, Mohan SV, Ping TL, Bin TA, Din T, Haron J, et al. Plasma circulating mirnas profiling for identification of potential breast cancer early detection biomarkers. Asian Pacific Journal of Cancer Prevention: APJCP. 2021;22(5):1375-81. https://doi.org/10.31557/APJCP.2021.22.5.1375.
[13] Mavaddat N, Michailidou K, Dennis J, Lush M, Fachal L, Lee A, et al. Polygenic risk scores for prediction of breast cancer and breast cancer subtypes. The American Journal of Human Genetics. 2019;104(1):21-34. https://doi.org/10.1016/j.ajhg.2018.11.002.
[14] Yu D, Tong Y, Guo X, Feng L, Jiang Z, Ying S, et al. Diagnostic value of concentration of circulating cell-free DNA in breast cancer: a meta-analysis. Frontiers in oncology. 2019;9:95. https://doi.org/10.3389/fonc.2019.00095.
[15] Lubowicka E, Przylipiak A, Zajkowska M, Piskór BM, Malinowski P, Fiedorowicz W, et al. Plasma chemokine CCL2 and its receptor CCR2 concentrations as diagnostic biomarkers for breast cancer patients. BioMed research international. 2018. https://doi.org/10.1155/2018/2124390.
[16] Khorrami S, Tavakoli M, Safari E. Clinical value of serum S100A8/A9 and CA15-3 in the diagnosis of breast cancer. Iranian Journal of Pathology. 2019;14(2):104-12. https://doi.org/10.30699/IJP.14.2.104.
[17] Mo MH, Chen L, Fu Y, Wang W, Fu SW. Cell-free circulating miRNA biomarkers in cancer. Journal of Cancer. 2012;3:432-48. https://doi.org/10.7150/jca.4919.
[18] Li C, Zhou T, Chen J, Li R, Chen H, Luo S, et al. The role of Exosomal miRNAs in cancer. Journal of translational medicine. 2022;20(1):1-5. https://doi.org/10.1186/s12967-021-03215-4.
[19] Davarinejad O, Mohammadi P, Ghavi D, Golmohammadi F, Foruzandeh Z, Alivand M, et al. Identifying miRNA signature for predicting and treatment of breast cancer using the transcriptomic data of 7,000 breast tumors. 2022. https://doi.org/10.21203/rs.3.rs-1551331/v1.
[20] Hasanoğlu S, Göncü BS, Yücesan E, Atasoy S, Kayali Y, Kandaş NÖ. Investigating differential miRNA expression profiling using serum and urine specimensfor detecting potential biomarkers for early prostate cancer diagnosis. Turkish journal of medical sciences. 2021;51(4):1764-74. https://doi.org/10.3906/sag-2010-183.
[21] Hoshino I. The usefulness of microRNA in urine and saliva as a biomarker of gastroenterological cancer. International Journal of Clinical Oncology. 2021;26:1431-40. https://doi.org/10.1007/s10147-021-01911-1.
[22] Chen H, Liu H, Zou H, Chen R, Dou Y, Sheng S, et al. Evaluation of plasma miR-21 and miR-152 as diagnostic biomarkers for common types of human cancers. Journal of cancer. 2016;7(5):490-99. https://doi.org/10.7150/jca.12351.
[23] Boeri M, Verri C, Conte D, Roz L, Modena P, Facchinetti F, et al. MicroRNA signatures in tissues and plasma predict development and prognosis of computed tomography detected lung cancer. Proceedings of the National Academy of Sciences. 2011;108(9):3713-8. https://doi.org/10.1073/pnas.1100048108.
[24] Aggarwal V, Priyanka K, Tuli HS. Emergence of circulating MicroRNAs in breast cancer as diagnostic and therapeutic efficacy biomarkers. Molecular diagnosis & therapy. 2020;24(2):153-73. https://doi.org/10.1007/s40291-020-00447-w.
[25] Cui Z, Lin D, Song W, Chen M, Li D. Diagnostic value of circulating microRNAs as biomarkers for breast cancer: a meta-analysis study. Tumor Biology. 2015;36:829-39. https://doi.org/10.1007/s13277-014-2700-8.
[26] Liu L, Wang S, Cao X, Liu J. Analysis of circulating microRNA biomarkers for breast cancer detection: a meta-analysis. Tumor Biology. 2014;35:12245-53. https://doi.org/10.1007/s13277-014-2533-5.
[27] Tugwell P, Tovey D. PRISMA 2020. Journal of Clinical Epidemiology. 2021;134:A5-6. https://doi.org/10.1016/j.jclinepi.2021.04.008.
[28] Whiting PF, Rutjes AW, Westwood ME, Mallett S, Deeks JJ, Reitsma JB, et al. QUADAS-2: a revised tool for the quality assessment of diagnostic accuracy studies. Annals of internal medicine. 2011;155(8):529-36. https://doi.org/10.7326/0003-4819-155-8-201110180-00009.
[29] Rasheed NW. Circulating microRNA-92a as biomarkers for primary woman breast cancer Iraq population. Journal of Population Therapeutics and Clinical Pharmacology. 2023;30(1):344-54. https://doi.org/10.47750/jptcp.2023.1093.
[30] Zou R, Loke SY, Tang YC, Too HP, Zhou L, Lee AS, et al. Development and validation of a circulating microRNA panel for the early detection of breast cancer. British journal of cancer. 2022;126(3):472-81. https://doi.org/10.1038/s41416-021-01593-6.
[31] Li X, Tang X, Li K, Lu L. Evaluation of serum microRNAs (miR-9-5p, miR-17-5p, and miR-148a-3p) as potential biomarkers of breast cancer. BioMed Research International. 2022. https://doi.org/10.1155/2022/9961412.
[32] Sadeghi H, Kamal A, Ahmadi M, Najafi H, Sharifi Zarchi A, Haddad P, et al. A novel panel of blood-based microRNAs capable of discrimination between benign breast disease and breast cancer at early stages. RNA biology. 2021;18(sup2):747-56. https://doi.org/10.1080/15476286.2021.1989218.
[33] Swellam M, Zahran RF, Ghonem SA, Abdel-Malak C. Serum MiRNA-27a as potential diagnostic nucleic marker for breast cancer. Archives of Physiology and Biochemistry. 2021;127(1):90-6. https://doi.org/10.1080/13813455.2019.1616765.
[34] Zou R, Loke SY, Tan VK, Quek ST, Jagmohan P, Tang YC, et al. Development of a microRNA panel for classification of abnormal mammograms for breast cancer. Cancers. 2021;13(9):2130. https://doi.org/10.3390/cancers13092130.
[35] Shaker O, Ayeldeen G, Abdelhamid A. The impact of single nucleotide polymorphism in the long non-coding MEG3 gene on microRNA-182 and microRNA-29 expression levels in the development of breast cancer in Egyptian women. Frontiers in Genetics. 2021;12:683809. https://doi.org/10.3389/fgene.2021.683809.
[36] Diansyah MN, Prayogo AA, Sedana MP, Savitri M, Romadhon PZ, Amrita PN, et al. Early detection breast cancer: role of circulating plasma miRNA-21 expression as apotential screening biomarker. Turkish Journal of Medical Sciences. 2021;51(2):562-9. https://doi.org/10.3906/sag-2005-138.
[37] Zou X, Xia T, Li M, Wang T, Liu P, Zhou X, et al. MicroRNA profiling in serum: Potential signatures for breast cancer diagnosis. Cancer Biomarkers. 2021;30(1):41-53. https://doi.org/10.3233/CBM-201547.
[38] Nashtahosseini Z, Aghamaali MR, Sadeghi F, Heydari N, Parsian H. Circulating status of microRNAs 660‐5p and 210‐3p in breast cancer patients. The Journal of Gene Medicine. 2021;23(4):e3320. https://doi.org/10.1002/jgm.3320.
[39] Jang JY, Kim YS, Kang KN, Kim KH, Park YJ, Kim CW. Multiple microRNAs as biomarkers for early breast cancer diagnosis. Molecular and clinical oncology. 2021;14(2). https://doi.org/10.3892/mco.2020.2193.
[40] Hosseini Mojahed F, Aalami AH, Pouresmaeil V, Amirabadi A, Qasemi Rad M, Sahebkar A. Clinical evaluation of the diagnostic role of MicroRNA-155 in breast cancer. International Journal of Genomics. 2020. https://doi.org/10.1155/2020/9514831.
[41] Kim J, Park S, Hwang D, Kim SI, Lee H. Diagnostic value of circulating miR-202 in early-stage breast cancer in South Korea. Medicina. 2020;56(7):340. https://doi.org/10.3390/medicina56070340.
[42] Pastor-Navarro B, García-Flores M, Fernández-Serra A, Blanch-Tormo S, Martínez de Juan F, Martínez-Lapiedra C, et al. A tetra-panel of serum circulating mirnas for the diagnosis of the four most prevalent tumor types. International Journal of Molecular Sciences. 2020;21(8):2783. https://doi.org/10.3390/ijms21082783.
[43] Han S, Li P, Wang D, Yan H. Dysregulation of serum miR-1204 and its potential as a biomarker for the diagnosis and prognosis of breast cancer. Revista da Associação Médica Brasileira. 2020;66(6):732-6. https://doi.org/10.1590/1806-9282.66.6.732.
[44] Ashirbekov Y, Abaildayev A, Omarbayeva N, Botbayev D, Belkozhayev A, Askandirova A, et al. Combination of circulating miR-145-5p/miR-191-5p as biomarker for breast cancer detection. PeerJ. 2020;8:e10494. https://doi.org/10.7717/peerj.10494.
[45] Ibrahim AM, Said MM, Hilal AM, Medhat AM, Abd Elsalam IM. Candidate circulating microRNAs as potential diagnostic and predictive biomarkers for the monitoring of locally advanced breast cancer patients. Tumor Biology. 2020;42(10):1010428320963811. https://doi.org/10.1177/1010428320963811.
[46] Swellam M, Ramadan A, El-Hussieny EA, Bakr NM, Hassan NM, Sobeih ME, et al. Clinical significance of blood‐based miRNAs as diagnostic and prognostic nucleic acid markers in breast cancer: Comparative to conventional tumor markers. Journal of cellular biochemistry. 2019;120(8):12321-30. https://doi.org/10.1002/jcb.28496.
[47] Peña-Cano MI, Saucedo R, Morales-Avila E, Valencia J, Zavala-Moha JA, López A. Deregulated microRNAs and adiponectin in postmenopausal women with breast cancer. Gynecologic and Obstetric Investigation. 2019;84(4):369-77. https://doi.org/10.1159/000496340.
[48] Motamedi M, Hashemzadeh Chaleshtori M, Ghasemi S, Mokarian F. Plasma level of miR-21 and miR-451 in primary and recurrent breast cancer patients. Breast Cancer: Targets and Therapy. 2019:293-301.
[49] Swellam M, Zahran RF, Abo El-Sadat Taha H, El-Khazragy N, Abdel-Malak C. Role of some circulating MiRNAs on breast cancer diagnosis. Archives of Physiology and Biochemistry. 2019;125(5):456-64. https://doi.org/10.1080/13813455.2018.1482355.
[50] Li M, Zou X, Xia T, Wang T, Liu P, Zhou X, et al. A five-miRNA panel in plasma was identified for breast cancer diagnosis. Cancer medicine. 2019;8(16):7006-17. https://doi.org/10.1002/cam4.2572.
[51] Fang R, Zhu Y, Hu L, Khadka VS, Ai J, Zou H, et al. Plasma microRNA pair panels as novel biomarkers for detection of early stage breast cancer. Frontiers in physiology. 2019;9:1879. https://doi.org/10.3389/fphys.2018.01879.
[52] Soleimanpour E, Babaei E, Hosseinpour-Feizi MA, Montazeri V. Circulating miR-21 and miR-155 as potential noninvasive biomarkers in Iranian Azeri patients with breast carcinoma. Journal of Cancer Research and Therapeutics. 2019;15(5):1092-7. https://doi.org/10.4103/jcrt.JCRT_1227_16.
[53] Heydari N, Nikbakhsh N, Sadeghi F, Farnoush N, Khafri S, Bastami M, et al. Overexpression of serum MicroRNA-140-3p in premenopausal women with newly diagnosed breast cancer. Gene. 2018;655:25-9. https://doi.org/10.1016/j.gene.2018.02.032.
[54] Li M, Zhou Y, Xia T, Zhou X, Huang Z, Zhang H, et al. Circulating microRNAs from the miR-106a–363 cluster on chromosome X as novel diagnostic biomarkers for breast cancer. Breast cancer research and treatment. 2018;170:257-70. https://doi.org/10.1007/s10549-018-4757-3.
 [55] Yu X, Liang J, Xu J, Li X, Xing S, Li H, et al. Identification and validation of circulating MicroRNA signatures for breast cancer early detection based on large scale tissue-derived data. Journal of breast cancer. 2018;21(4):363-70. https://doi.org/10.4048/jbc.2018.21.e56.
[56] Zhang K, Wang YW, Wang YY, Song Y, Zhu J, Si PC, et al. Identification of microRNA biomarkers in the blood of breast cancer patients based on microRNA profiling. Gene. 2017;619:10-20. https://doi.org/10.1016/j.gene.2017.03.038.
[57] Zhang G, Zhang W, Li B, Stringer-Reasor E, Chu C, Sun L, et al. MicroRNA-200c and microRNA-141 are regulated by a FOXP3-KAT2B axis and associated with tumor metastasis in breast cancer. Breast Cancer Research. 2017;19(1):1-13. https://doi.org/10.1186/s13058-017-0858-x.
[58] Frères P, Wenric S, Boukerroucha M, Fasquelle C, Thiry J, Bovy N, et al. Circulating microRNA-based screening tool for breast cancer. Oncotarget. 2016;7(5):5416-28. https://doi.org/10.18632/oncotarget.6786.
[59] Antolín S, Calvo L, Blanco-Calvo M, Santiago MP, Lorenzo-Patiño MJ, Haz-Conde M, et al. Circulating miR-200c and miR-141 and outcomes in patients with breast cancer. BMC cancer. 2015;15(1):1-15. https://doi.org/10.1186/s12885-015-1238-5.
[60] Heneghan HM, Miller N, Lowery AJ, Sweeney KJ, Newell J, Kerin MJ. Circulating microRNAs as novel minimally invasive biomarkers for breast cancer. Annals of surgery. 2010;251(3):499-505. https://doi.org/10.1097/SLA.0b013e3181cc939f.
[61] Iorio MV, Croce CM. MicroRNAs in cancer: small molecules with a huge impact. Journal of clinical oncology. 2009;27(34):5848-56. https://doi.org/10.1200/JCO.2009.24.0317.
[62] Wang H, Peng R, Wang J, Qin Z, Xue L. Circulating microRNAs as potential cancer biomarkers: the advantage and disadvantage. Clinical epigenetics. 2018;10(1):1-10. https://doi.org/10.1186/s13148-018-0492-1.
[63] Tiberio P, Callari M, Angeloni V, Daidone MG, Appierto V. Challenges in using circulating miRNAs as cancer biomarkers. BioMed research international. 2015. https://doi.org/10.1155/2015/731479.
[64] Felekkis K, Papaneophytou C. Challenges in using circulating micro-RNAs as biomarkers for cardiovascular diseases. International Journal of Molecular Sciences. 2020;21(2):561. https://doi.org/10.3390/ijms21020561.
[65] Kirschner MB, Edelman JJ, Kao SC, Vallely MP, Van Zandwijk N, Reid G. The impact of hemolysis on cell-free microRNA biomarkers. Frontiers in genetics. 2013;4:94. https://doi.org/10.3389/fgene.2013.00094.
[66] Pizzamiglio S, Zanutto S, Ciniselli CM, Belfiore A, Bottelli S, Gariboldi M, et al. A methodological procedure for evaluating the impact of hemolysis on circulating microRNAs. Oncology letters. 2017;13(1):315-20. https://doi.org/10.3892/ol.2016.5452.
[67] Yamada A, Cox MA, Gaffney KA, Moreland A, Boland CR, Goel A. Technical factors involved in the measurement of circulating microRNA biomarkers for the detection of colorectal neoplasia. PLoS One. 2014;9(11):e112481. https://doi.org/10.1371/journal.pone.0112481.