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miRNAs as therapeutic predictors and prognostic biomarkers of neoadjuvant chemotherapy in breast cancer: a systematic review and meta-analysis

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Abstract

Purpose

Accumulating evidence has shown that microRNAs (miRNAs) are promising biomarkers of neoadjuvant chemotherapy (NAC) response in breast cancer (BC). However, their predictive roles remain controversial. Thus, this systematic review and meta-analysis aimed to describe the role of miRNA expression in NAC response and prognosis in BC to increase statistical power and improve translation.

Methods

A systematic review of electronic databases for relevant studies was conducted following PRISMA guidelines. Data were extracted, collated, and combined by odds ratio (OR) and hazard ratio (HR) with 95% confidence intervals (CIs) to estimate the strength of the associations.

Results

Of the 560 articles screened, 59 studies were included in our systematic review, and 5 studies were included in the subsequent meta-analysis. Sixty of 123 miRNAs were found to be related with NAC response and an elevated baseline miR-7 level in tissues was associated with a higher pathological complete response rate (OR 5.63; 95% CI 2.15–14.79; P = 0.0004). The prognostic value of 39 miRNAs was also studied. Of them, 26 miRNAs were found to be associated with survival. Pooled HRs indicated that patients with increased levels of serum miR-21 from baseline to the end of the second NAC cycle and from baseline to the end of NAC had a worse disease-free survival than those with decreased levels.

Conclusion

Our results highlight that a large number of miRNAs have possible associations with NAC response and prognosis in BC patients. Further well-designed studies are needed to elucidate the molecular mechanisms underlying these associations.

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Data availability

The datasets generated during and/or analyzed during the current study are available in Online Electronic Supplementary Materials.

References

  1. Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F (2021) Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 71:209–249. https://doi.org/10.3322/caac.21660

    Article  PubMed  Google Scholar 

  2. Pernaut C, Lopez F, Ciruelos E (2018) Standard neoadjuvant treatment in early/locally advanced breast cancer. Breast Care (Basel) 13:244–249. https://doi.org/10.1159/000491759

    Article  Google Scholar 

  3. Colomer R, Saura C, Sanchez-Rovira P, Pascual T, Rubio IT, Burgues O, Marcos L, Rodriguez CA, Martin M, Lluch A (2019) Neoadjuvant management of early breast cancer: a clinical and investigational position statement. Oncologist 24:603–611. https://doi.org/10.1634/theoncologist.2018-0228

    Article  PubMed  PubMed Central  Google Scholar 

  4. Berruti A, Amoroso V, Gallo F, Bertaglia V, Simoncini E, Pedersini R, Ferrari L, Bottini A, Bruzzi P, Sormani MP (2014) Pathologic complete response as a potential surrogate for the clinical outcome in patients with breast cancer after neoadjuvant therapy: a meta-regression of 29 randomized prospective studies. J Clin Oncol 32:3883–3891. https://doi.org/10.1200/JCO.2014.55.2836

    Article  PubMed  Google Scholar 

  5. Cortazar P, Zhang L, Untch M, Mehta K, Costantino JP, Wolmark N, Bonnefoi H, Cameron D, Gianni L, Valagussa P, Swain SM, Prowell T, Loibl S, Wickerham DL, Bogaerts J, Baselga J, Perou C, Blumenthal G, Blohmer J, Mamounas EP, Bergh J, Semiglazov V, Justice R, Eidtmann H, Paik S, Piccart M, Sridhara R, Fasching PA, Slaets L, Tang S, Gerber B, Geyer CE Jr, Pazdur R, Ditsch N, Rastogi P, Eiermann W, von Minckwitz G (2014) Pathological complete response and long-term clinical benefit in breast cancer: the CTNeoBC pooled analysis. Lancet 384:164–172. https://doi.org/10.1016/S0140-6736(13)62422-8

    Article  PubMed  Google Scholar 

  6. Wang-Lopez Q, Chalabi N, Abrial C, Radosevic-Robin N, Durando X, Mouret-Reynier MA, Benmammar KE, Kullab S, Bahadoor M, Chollet P, Penault-Llorca F, Nabholtz JM (2015) Can pathologic complete response (pCR) be used as a surrogate marker of survival after neoadjuvant therapy for breast cancer? Crit Rev Oncol Hematol 95:88–104. https://doi.org/10.1016/j.critrevonc.2015.02.011

    Article  PubMed  Google Scholar 

  7. Torrisi R, Marrazzo E, Agostinetto E, De Sanctis R, Losurdo A, Masci G, Tinterri C, Santoro A (2021) Neoadjuvant chemotherapy in hormone receptor-positive/HER2-negative early breast cancer: when, why and what? Crit Rev Oncol Hematol 160:103280. https://doi.org/10.1016/j.critrevonc.2021.103280

    Article  PubMed  Google Scholar 

  8. Bartel DP (2004) MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 116:281–297. https://doi.org/10.1016/s0092-8674(04)00045-5

    Article  CAS  PubMed  Google Scholar 

  9. Casey MC, Sweeney KJ, Brown JA, Kerin MJ (2016) Exploring circulating micro-RNA in the neoadjuvant treatment of breast cancer. Int J Cancer 139:12–22. https://doi.org/10.1002/ijc.29985

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Jayaraj R, Nayagam SG, Kar A, Sathyakumar S, Mohammed H, Smiti M, Sabarimurugan S, Kumarasamy C, Priyadharshini T, Gothandam KM, Ramesh N, Gupta A, Baxi S, Swamiappan S, Krishnan S (2019) Clinical theragnostic relationship between drug-resistance specific miRNA expressions, chemotherapeutic resistance, and sensitivity in breast cancer: a systematic review and meta-analysis. Cells. https://doi.org/10.3390/cells8101250

    Article  PubMed  PubMed Central  Google Scholar 

  11. Zhao R, Wu J, Jia W, Gong C, Yu F, Ren Z, Chen K, He J, Su F (2011) Plasma miR-221 as a predictive biomarker for chemoresistance in breast cancer patients who previously received neoadjuvant chemotherapy. Onkologie 34:675–680. https://doi.org/10.1159/000334552

    Article  CAS  PubMed  Google Scholar 

  12. Zhu Y, Yu F, Jiao Y, Feng J, Tang W, Yao H, Gong C, Chen J, Su F, Zhang Y, Song E (2011) Reduced miR-128 in breast tumor-initiating cells induces chemotherapeutic resistance via Bmi-1 and ABCC5. Clin Cancer Res Off J Am Assoc Cancer Res 17:7105–7115. https://doi.org/10.1158/1078-0432.CCR-11-0071

    Article  CAS  Google Scholar 

  13. Muller V, Gade S, Steinbach B, Loibl S, von Minckwitz G, Untch M, Schwedler K, Lubbe K, Schem C, Fasching PA, Mau C, Pantel K, Schwarzenbach H (2014) Changes in serum levels of miR-21, miR-210, and miR-373 in HER2-positive breast cancer patients undergoing neoadjuvant therapy: a translational research project within the Geparquinto trial. Breast Cancer Res Treat 147:61–68. https://doi.org/10.1007/s10549-014-3079-3

    Article  CAS  PubMed  Google Scholar 

  14. Liu B, Su F, Chen M, Li Y, Qi X, Xiao J, Li X, Liu X, Liang W, Zhang Y, Zhang J (2017) Serum miR-21 and miR-125b as markers predicting neoadjuvant chemotherapy response and prognosis in stage II/III breast cancer. Hum Pathol 64:44–52. https://doi.org/10.1016/j.humpath.2017.03.016

    Article  CAS  PubMed  Google Scholar 

  15. Liu B, Su F, Lv X, Zhang W, Shang X, Zhang Y, Zhang J (2019) Serum microRNA-21 predicted treatment outcome and survival in HER2-positive breast cancer patients receiving neoadjuvant chemotherapy combined with trastuzumab. Cancer Chemother Pharmacol 84:1039–1049. https://doi.org/10.1007/s00280-019-03937-9

    Article  CAS  PubMed  Google Scholar 

  16. Garcia-Garcia F, Salinas-Vera YM, Garcia-Vazquez R, Marchat LA, Rodriguez-Cuevas S, Lopez-Gonzalez JS, Carlos-Reyes A, Ramos-Payan R, Aguilar-Medina M, Perez-Plasencia C, Ruiz-Garcia E, Lopez-Camarillo C (2019) miR1455p is associated with pathological complete response to neoadjuvant chemotherapy and impairs cell proliferation by targeting TGFbetaR2 in breast cancer. Oncol Rep 41:3527–3534. https://doi.org/10.3892/or.2019.7102

    Article  CAS  PubMed  Google Scholar 

  17. Al-Khanbashi M, Caramuta S, Alajmi AM, Al-Haddabi I, Al-Riyami M, Lui WO, Al-Moundhri MS (2016) Tissue and serum miRNA profile in locally advanced breast cancer (LABC) in response to neo-adjuvant chemotherapy (NAC) treatment. PLoS ONE 11:e0152032. https://doi.org/10.1371/journal.pone.0152032

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Zhu W, Liu M, Fan Y, Ma F, Xu N, Xu B (2018) Dynamics of circulating microRNAs as a novel indicator of clinical response to neoadjuvant chemotherapy in breast cancer. Cancer Med 7:4420–4433. https://doi.org/10.1002/cam4.1723

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Moher D, Liberati A, Tetzlaff J, Altman DG, PRISMA Group (2009) Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. BMJ 339:b2535. https://doi.org/10.1136/bmj.b2535

    Article  PubMed  PubMed Central  Google Scholar 

  20. Tierney JF, Stewart LA, Ghersi D, Burdett S, Sydes MR (2007) Practical methods for incorporating summary time-to-event data into meta-analysis. Trials 8:16. https://doi.org/10.1186/1745-6215-8-16

    Article  PubMed  PubMed Central  Google Scholar 

  21. Stang A (2010) Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol 25:603–605. https://doi.org/10.1007/s10654-010-9491-z

    Article  PubMed  Google Scholar 

  22. Gong C, Yao Y, Wang Y, Liu B, Wu W, Chen J, Su F, Yao H, Song E (2011) Up-regulation of miR-21 mediates resistance to trastuzumab therapy for breast cancer. J Biol Chem 286:19127–19137. https://doi.org/10.1074/jbc.M110.216887

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Chen J, Tian W, Cai H, He H, Deng Y (2012) Down-regulation of microRNA-200c is associated with drug resistance in human breast cancer. Med Oncol 29:2527–2534. https://doi.org/10.1007/s12032-011-0117-4

    Article  CAS  PubMed  Google Scholar 

  24. Jung EJ, Santarpia L, Kim J, Esteva FJ, Moretti E, Buzdar AU, Di Leo A, Le XF, Bast RC Jr, Park ST, Pusztai L, Calin GA (2012) Plasma microRNA 210 levels correlate with sensitivity to trastuzumab and tumor presence in breast cancer patients. Cancer 118:2603–2614. https://doi.org/10.1002/cncr.26565

    Article  CAS  PubMed  Google Scholar 

  25. Li XJ, Ji MH, Zhong SL, Zha QB, Xu JJ, Zhao JH, Tang JH (2012) MicroRNA-34a modulates chemosensitivity of breast cancer cells to adriamycin by targeting Notch1. Arch Med Res 43:514–521. https://doi.org/10.1016/j.arcmed.2012.09.007

    Article  CAS  PubMed  Google Scholar 

  26. Wang H, Tan G, Dong L, Cheng L, Li K, Wang Z, Luo H (2012) Circulating miR-125b as a marker predicting chemoresistance in breast cancer. PLoS ONE 7:e34210. https://doi.org/10.1371/journal.pone.0034210

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Wu X, Somlo G, Yu Y, Palomares MR, Li AX, Zhou W, Chow A, Yen Y, Rossi JJ, Gao H, Wang J, Yuan YC, Frankel P, Li S, Ashing-Giwa KT, Sun G, Wang Y, Smith R, Robinson K, Ren X, Wang SE (2012) De novo sequencing of circulating miRNAs identifies novel markers predicting clinical outcome of locally advanced breast cancer. J Transl Med 10:42. https://doi.org/10.1186/1479-5876-10-42

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Zhu Y, Wu J, Li S, Ma R, Cao H, Ji M, Jing C, Tang J (2013) The function role of miR-181a in chemosensitivity to adriamycin by targeting Bcl-2 in low-invasive breast cancer cells. Cell Physiol Biochem Int J Exp Cell Physiol Biochem Pharmacol 32:1225–1237. https://doi.org/10.1159/000354521

    Article  CAS  Google Scholar 

  29. Gezer U, Keskin S, Igci A, Tukenmez M, Tiryakioglu D, Cetinkaya M, Disci R, Dalay N, Eralp Y (2014) Abundant circulating microRNAs in breast cancer patients fluctuate considerably during neoadjuvant chemotherapy. Oncol Lett 8:845–848. https://doi.org/10.3892/ol.2014.2188

    Article  PubMed  PubMed Central  Google Scholar 

  30. Jiang L, He D, Yang D, Chen Z, Pan Q, Mao A, Cai Y, Li X, Xing H, Shi M, Chen Y, Bruce IC, Wang T, Jin L, Qi X, Hua D, Jin J, Ma X (2014) MiR-489 regulates chemoresistance in breast cancer via epithelial mesenchymal transition pathway. FEBS Lett 588:2009–2015. https://doi.org/10.1016/j.febslet.2014.04.024

    Article  CAS  PubMed  Google Scholar 

  31. Kolacinska A, Morawiec J, Fendler W, Malachowska B, Morawiec Z, Szemraj J, Pawlowska Z, Chowdhury D, Choi YE, Kubiak R, Pakula L, Zawlik I (2014) Association of microRNAs and pathologic response to preoperative chemotherapy in triple negative breast cancer: preliminary report. Mol Biol Rep 41:2851–2857. https://doi.org/10.1007/s11033-014-3140-7

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Li Q, Liu M, Ma F, Luo Y, Cai R, Wang L, Xu N, Xu B (2014) Circulating miR-19a and miR-205 in serum may predict the sensitivity of luminal A subtype of breast cancer patients to neoadjuvant chemotherapy with epirubicin plus paclitaxel. PLoS ONE 9:e104870. https://doi.org/10.1371/journal.pone.0104870

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Palmieri C, Cleator S, Kilburn LS, Kim SB, Ahn SH, Beresford M, Gong G, Mansi J, Mallon E, Reed S, Mousa K, Fallowfield L, Cheang M, Morden J, Page K, Guttery DS, Rghebi B, Primrose L, Shaw JA, Thompson AM, Bliss JM, Coombes RC (2014) NEOCENT: a randomised feasibility and translational study comparing neoadjuvant endocrine therapy with chemotherapy in ER-rich postmenopausal primary breast cancer. Breast Cancer Res Treat 148:581–590. https://doi.org/10.1007/s10549-014-3183-4

    Article  CAS  PubMed  Google Scholar 

  34. Zhao FL, Dou YC, Wang XF, Han DC, Lv ZG, Ge SL, Zhang YK (2014) Serum microRNA-195 is down-regulated in breast cancer: a potential marker for the diagnosis of breast cancer. Mol Biol Rep 41:5913–5922. https://doi.org/10.1007/s11033-014-3466-1

    Article  CAS  PubMed  Google Scholar 

  35. De Mattos-Arruda L, Bottai G, Nuciforo PG, Di Tommaso L, Giovannetti E, Peg V, Losurdo A, Perez-Garcia J, Masci G, Corsi F, Cortes J, Seoane J, Calin GA, Santarpia L (2015) MicroRNA-21 links epithelial-to-mesenchymal transition and inflammatory signals to confer resistance to neoadjuvant trastuzumab and chemotherapy in HER2-positive breast cancer patients. Oncotarget 6:37269–37280. https://doi.org/10.18632/oncotarget.5495

    Article  PubMed  PubMed Central  Google Scholar 

  36. Freres P, Josse C, Bovy N, Boukerroucha M, Struman I, Bours V, Jerusalem G (2015) Neoadjuvant chemotherapy in breast cancer patients induces miR-34a and miR-122 expression. J Cell Physiol 230:473–481. https://doi.org/10.1002/jcp.24730

    Article  CAS  PubMed  Google Scholar 

  37. Wang G, Wang L, Sun S, Wu J, Wang Q (2015) Quantitative measurement of serum microRNA-21 expression in relation to breast cancer metastasis in Chinese females. Ann Lab Med 35:226–232. https://doi.org/10.3343/alm.2015.35.2.226

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Wu J, Li S, Jia W, Deng H, Chen K, Zhu L, Yu F, Su F (2015) Reduced Let-7a is associated with chemoresistance in primary breast cancer. PLoS ONE 10:e0133643. https://doi.org/10.1371/journal.pone.0133643

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Zheng Y, Li S, Boohaker RJ, Liu X, Zhu Y, Zhai L, Li H, Gu F, Fan Y, Lang R, Liu F, Qian X, Xu B, Fu L (2015) A microRNA expression signature in taxane-anthracycline-based neoadjuvant chemotherapy response. J Cancer 6:671–677. https://doi.org/10.7150/jca.11616

    Article  PubMed  PubMed Central  Google Scholar 

  40. Chen X, Lu P, Wang DD, Yang SJ, Wu Y, Shen HY, Zhong SL, Zhao JH, Tang JH (2016) The role of miRNAs in drug resistance and prognosis of breast cancer formalin-fixed paraffin-embedded tissues. Gene 595:221–226. https://doi.org/10.1016/j.gene.2016.10.015

    Article  CAS  PubMed  Google Scholar 

  41. Gu X, Xue JQ, Han SJ, Qian SY, Zhang WH (2016) Circulating microRNA-451 as a predictor of resistance to neoadjuvant chemotherapy in breast cancer. Cancer Biomark A 16:395–403. https://doi.org/10.3233/CBM-160578

    Article  CAS  Google Scholar 

  42. Hu Y, Qiu Y, Yague E, Ji W, Liu J, Zhang J (2016) miRNA-205 targets VEGFA and FGF2 and regulates resistance to chemotherapeutics in breast cancer. Cell Death Dis 7:e2291. https://doi.org/10.1038/cddis.2016.194

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Li S, Bi T, Wang R, Gao X, Zhou J (2016) Circulating miR-663 as a novel biomarker for chemo-resistance in breast cancer of neoadjuvant chemotherapy. Int J Clin Exp Med 9:4002–4008

    CAS  Google Scholar 

  44. Sha LY, Zhang Y, Wang W, Sui X, Liu SK, Wang T, Zhang H (2016) miR-18a upregulation decreases Dicer expression and confers paclitaxel resistance in triple negative breast cancer. Eur Rev Med Pharmacol Sci 20:2201–2208

    PubMed  Google Scholar 

  45. Xue J, Chi Y, Chen Y, Huang S, Ye X, Niu J, Wang W, Pfeffer LM, Shao ZM, Wu ZH, Wu J (2016) miRNA-621 sensitizes breast cancer to chemotherapy by suppressing FBXO11 and enhancing p53 activity. Oncogene 35:448–458. https://doi.org/10.1038/onc.2015.96

    Article  CAS  PubMed  Google Scholar 

  46. Garcia-Vazquez R, Ruiz-Garcia E, Meneses Garcia A, Astudillo-de la Vega H, Lara-Medina F, Alvarado-Miranda A, Maldonado-Martinez H, Gonzalez-Barrios JA, Campos-Parra AD, Rodriguez Cuevas S, Marchat LA, Lopez-Camarillo C (2017) A microRNA signature associated with pathological complete response to novel neoadjuvant therapy regimen in triple-negative breast cancer. Tumour Biol J Int Soc Oncodev Biol Med 39:1010428317702899. https://doi.org/10.1177/1010428317702899

    Article  CAS  Google Scholar 

  47. Liu B, Su F, Li Y, Qi X, Liu X, Liang W, You K, Zhang Y, Zhang J (2017) Changes of serum miR34a expression during neoadjuvant chemotherapy predict the treatment response and prognosis in stage II/III breast cancer. Biomed Pharmacother 88:911–917. https://doi.org/10.1016/j.biopha.2017.01.133

    Article  CAS  PubMed  Google Scholar 

  48. Ohzawa H, Miki A, Teratani T, Shiba S, Sakuma Y, Nishimura W, Noda Y, Fukushima N, Fujii H, Hozumi Y, Mukai H, Yasuda Y (2017) Usefulness of miRNA profiles for predicting pathological responses to neoadjuvant chemotherapy in patients with human epidermal growth factor receptor 2-positive breast cancer. Oncol Lett 13:1731–1740. https://doi.org/10.3892/ol.2017.5628

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Raychaudhuri M, Bronger H, Buchner T, Kiechle M, Weichert W, Avril S (2017) MicroRNAs miR-7 and miR-340 predict response to neoadjuvant chemotherapy in breast cancer. Breast Cancer Res Treat 162:511–521. https://doi.org/10.1007/s10549-017-4132-9

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Guo Q, Wen R, Shao B, Li Y, Jin X, Deng H, Wu J, Su F, Yu F (2018) Combined Let-7a and H19 signature: a prognostic index of progression-free survival in primary breast cancer patients. J Breast Cancer 21:142–149. https://doi.org/10.4048/jbc.2018.21.2.142

    Article  PubMed  PubMed Central  Google Scholar 

  51. Luengo-Gil G, Gonzalez-Billalabeitia E, Perez-Henarejos SA, Navarro Manzano E, Chaves-Benito A, Garcia-Martinez E, Garcia-Garre E, Vicente V, Ayala de la Pena F (2018) Angiogenic role of miR-20a in breast cancer. PLoS ONE 13:e0194638. https://doi.org/10.1371/journal.pone.0194638

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Stevic I, Muller V, Weber K, Fasching PA, Karn T, Marme F, Schem C, Stickeler E, Denkert C, van Mackelenbergh M, Salat C, Schneeweiss A, Pantel K, Loibl S, Untch M, Schwarzenbach H (2018) Specific microRNA signatures in exosomes of triple-negative and HER2-positive breast cancer patients undergoing neoadjuvant therapy within the GeparSixto trial. BMC Med 16:179. https://doi.org/10.1186/s12916-018-1163-y

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Wang XX, Ye FG, Zhang J, Li JJ, Chen QX, Lin PY, Song CG (2018) Serum miR-4530 sensitizes breast cancer to neoadjuvant chemotherapy by suppressing RUNX2. Cancer Manag Res 10:4393–4400. https://doi.org/10.2147/CMAR.S172205

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Yu SJ, Yang L, Hong Q, Kuang XY, Di GH, Shao ZM (2018) MicroRNA-200a confers chemoresistance by antagonizing TP53INP1 and YAP1 in human breast cancer. BMC Cancer 18:74. https://doi.org/10.1186/s12885-017-3930-0

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Di Cosimo S, Appierto V, Pizzamiglio S, Tiberio P, Iorio MV, Hilbers F, de Azambuja E, de la Pena L, Izquierdo M, Huober J, Baselga J, Piccart M, de Braud FG, Apolone G, Verderio P, Daidone MG (2019) Plasma miRNA levels for predicting therapeutic response to neoadjuvant treatment in HER2-positive breast cancer: results from the NeoALTTO Trial. Clin Cancer Res Off J Am Assoc Cancer Res 25:3887–3895. https://doi.org/10.1158/1078-0432.CCR-18-2507

    Article  Google Scholar 

  56. Garcia-Vazquez R, Marchat LA, Ruiz-Garcia E, Astudillo-de la Vega H, Meneses-Garcia A, Arce-Salinas C, Bargallo-Rocha E, Carlos-Reyes A, Lopez-Gonzalez JS, Perez-Plasencia C, Ramos-Payan R, Aguilar-Medina M, Lopez-Camarillo C (2019) MicroRNA-143 is associated with pathological complete response and regulates multiple signaling proteins in breast cancer. Technol Cancer Res Treat 18:1533033819827309. https://doi.org/10.1177/1533033819827309

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Hong T, Ding J, Li W (2019) miR-7 reverses breast cancer resistance to chemotherapy by targeting MRP1 And BCL2. OncoTargets Ther 12:11097–11105. https://doi.org/10.2147/OTT.S213780

    Article  CAS  Google Scholar 

  58. Huang J, Zhao M, Hu H, Wang J, Ang L, Zheng L (2019) MicroRNA-130a reduces drug resistance in breast cancer. Int J Clin Exp Pathol 12:2699–2705

    CAS  PubMed  PubMed Central  Google Scholar 

  59. Kassem NM, Makar WS, Kassem HA, Talima S, Tarek M, Hesham H, El-Desouky MA (2019) Circulating miR-34a and miR-125b as promising non invasive biomarkers in Egyptian locally advanced breast cancer patients. Asian Pac J Cancer Prev 20:2749–2755. https://doi.org/10.31557/APJCP.2019.20.9.2749

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Lindholm EM, Ragle Aure M, Haugen MH, Kleivi Sahlberg K, Kristensen VN, Nebdal D, Borresen-Dale AL, Lingjaerde OC, Engebraaten O (2019) miRNA expression changes during the course of neoadjuvant bevacizumab and chemotherapy treatment in breast cancer. Mol Oncol 13:2278–2296. https://doi.org/10.1002/1878-0261.12561

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Luengo-Gil G, Garcia-Martinez E, Chaves-Benito A, Conesa-Zamora P, Navarro-Manzano E, Gonzalez-Billalabeitia E, Garcia-Garre E, Martinez-Carrasco A, Vicente V, Ayala de la Pena F (2019) Clinical and biological impact of miR-18a expression in breast cancer after neoadjuvant chemotherapy. Cell Oncol (Dordr) 42:627–644. https://doi.org/10.1007/s13402-019-00450-2

    Article  CAS  Google Scholar 

  62. Rodriguez-Martinez A, de Miguel-Perez D, Ortega FG, Garcia-Puche JL, Robles-Fernandez I, Exposito J, Martorell-Marugan J, Carmona-Saez P, Garrido-Navas MDC, Rolfo C, Ilyine H, Lorente JA, Legueren M, Serrano MJ (2019) Exosomal miRNA profile as complementary tool in the diagnostic and prediction of treatment response in localized breast cancer under neoadjuvant chemotherapy. Breast Cancer Res 21:21. https://doi.org/10.1186/s13058-019-1109-0

    Article  PubMed  PubMed Central  Google Scholar 

  63. Chen Z, Pan T, Jiang D, Jin L, Geng Y, Feng X, Shen A, Zhang L (2020) The lncRNA-GAS5/miR-221-3p/DKK2 axis modulates ABCB1-mediated adriamycin resistance of breast cancer via the Wnt/beta-catenin signaling pathway. Mol Ther Nucleic Acids 19:1434–1448. https://doi.org/10.1016/j.omtn.2020.01.030

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Di Cosimo S, Appierto V, Pizzamiglio S, Silvestri M, Baselga J, Piccart M, Huober J, Izquierdo M, de la Pena L, Hilbers FS, de Azambuja E, Untch M, Pusztai L, Pritchard K, Nuciforo P, Vincent-Salomon A, Symmans F, Apolone G, de Braud FG, Iorio MV, Verderio P, Daidone MG (2020) Early modulation of circulating microRNAs levels in HER2-positive breast cancer patients treated with trastuzumab-based neoadjuvant therapy. Int J Mol Sci. https://doi.org/10.3390/ijms21041386

    Article  PubMed  PubMed Central  Google Scholar 

  65. Ibrahim AM, Said MM, Hilal AM, Medhat AM, Abd Elsalam IM (2020) Candidate circulating microRNAs as potential diagnostic and predictive biomarkers for the monitoring of locally advanced breast cancer patients. Tumour Biol J Int Soc Oncodev Biol Med 42:1010428320963811. https://doi.org/10.1177/1010428320963811

    Article  CAS  Google Scholar 

  66. McGuire A, Casey MC, Waldron RM, Heneghan H, Kalinina O, Holian E, McDermott A, Lowery AJ, Newell J, Dwyer RM, Miller N, Keane M, Brown JAL, Kerin MJ (2020) Prospective assessment of systemic microRNAs as markers of response to neoadjuvant chemotherapy in breast cancer. Cancers (Basel). https://doi.org/10.3390/cancers12071820

    Article  Google Scholar 

  67. Ritter A, Hirschfeld M, Berner K, Rucker G, Jager M, Weiss D, Medl M, Nothling C, Gassner S, Asberger J, Erbes T (2020) Circulating noncoding RNA biomarker potential in neoadjuvant chemotherapy of triple negative breast cancer? Int J Oncol 56:47–68. https://doi.org/10.3892/ijo.2019.4920

    Article  CAS  PubMed  Google Scholar 

  68. Salvador-Coloma C, Santaballa A, Sanmartin E, Calvo D, Garcia A, Hervas D, Cordon L, Quintas G, Ripoll F, Panadero J, Font de Mora J (2020) Immunosuppressive profiles in liquid biopsy at diagnosis predict response to neoadjuvant chemotherapy in triple-negative breast cancer. Eur J Cancer 139:119–134. https://doi.org/10.1016/j.ejca.2020.08.020

    Article  CAS  PubMed  Google Scholar 

  69. Zhang S, Wang Y, Wang Y, Peng J, Yuan C, Zhou L, Xu S, Lin Y, Du Y, Yang F, Zhang J, Dai H, Yin W, Lu J (2020) Serum miR-222-3p as a double-edged sword in predicting efficacy and trastuzumab-induced cardiotoxicity for HER2-positive breast cancer patients receiving neoadjuvant target therapy. Front Oncol 10:631. https://doi.org/10.3389/fonc.2020.00631

    Article  PubMed  PubMed Central  Google Scholar 

  70. Deng S, Zhang T, Chen X, Shi J, Meng M, Yue G, Xing S, Tian X, Yang X, Chen F, Li N (2021) Is there a correlation between miR-301a expression and neoadjuvant chemotherapy efficacy in breast cancer tissue? Biochem Biophys Rep 26:100947. https://doi.org/10.1016/j.bbrep.2021.100947

    Article  PubMed  PubMed Central  Google Scholar 

  71. Xing AY, Wang B, Li YH, Chen X, Wang YW, Liu HT, Gao P (2021) Identification of miRNA signature in breast cancer to predict neoadjuvant chemotherapy response. Pathol Oncol Res 27:1609753. https://doi.org/10.3389/pore.2021.1609753

    Article  PubMed  PubMed Central  Google Scholar 

  72. Yang Q, Zhao S, Shi Z, Cao L, Liu J, Pan T, Zhou D, Zhang J (2021) Chemotherapy-elicited exosomal miR-378a-3p and miR-378d promote breast cancer stemness and chemoresistance via the activation of EZH2/STAT3 signaling. J Exp Clin Cancer Res 40:120. https://doi.org/10.1186/s13046-021-01901-1

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Yanaihara N, Caplen N, Bowman E, Seike M, Kumamoto K, Yi M, Stephens RM, Okamoto A, Yokota J, Tanaka T, Calin GA, Liu CG, Croce CM, Harris CC (2006) Unique microRNA molecular profiles in lung cancer diagnosis and prognosis. Cancer Cell 9:189–198. https://doi.org/10.1016/j.ccr.2006.01.025

    Article  CAS  PubMed  Google Scholar 

  74. Yan LX, Huang XF, Shao Q, Huang MY, Deng L, Wu QL, Zeng YX, Shao JY (2008) MicroRNA miR-21 overexpression in human breast cancer is associated with advanced clinical stage, lymph node metastasis and patient poor prognosis. RNA 14:2348–2360. https://doi.org/10.1261/rna.1034808

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Zhang HL, Yang LF, Zhu Y, Yao XD, Zhang SL, Dai B, Zhu YP, Shen YJ, Shi GH, Ye DW (2011) Serum miRNA-21: elevated levels in patients with metastatic hormone-refractory prostate cancer and potential predictive factor for the efficacy of docetaxel-based chemotherapy. Prostate 71:326–331. https://doi.org/10.1002/pros.21246

    Article  CAS  PubMed  Google Scholar 

  76. Toiyama Y, Takahashi M, Hur K, Nagasaka T, Tanaka K, Inoue Y, Kusunoki M, Boland CR, Goel A (2013) Serum miR-21 as a diagnostic and prognostic biomarker in colorectal cancer. J Natl Cancer Inst 105:849–859. https://doi.org/10.1093/jnci/djt101

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Wang P, Zhuang L, Zhang J, Fan J, Luo J, Chen H, Wang K, Liu L, Chen Z, Meng Z (2013) The serum miR-21 level serves as a predictor for the chemosensitivity of advanced pancreatic cancer, and miR-21 expression confers chemoresistance by targeting FasL. Mol Oncol 7:334–345. https://doi.org/10.1016/j.molonc.2012.10.011

    Article  CAS  PubMed  Google Scholar 

  78. Qu K, Lin T, Pang Q, Liu T, Wang Z, Tai M, Meng F, Zhang J, Wan Y, Mao P, Dong X, Liu C, Niu W, Dong S (2016) Extracellular miRNA-21 as a novel biomarker in glioma: evidence from meta-analysis, clinical validation and experimental investigations. Oncotarget 7:33994–34010. https://doi.org/10.18632/oncotarget.9188

    Article  PubMed  PubMed Central  Google Scholar 

  79. Bautista-Sanchez D, Arriaga-Canon C, Pedroza-Torres A, De La Rosa-Velazquez IA, Gonzalez-Barrios R, Contreras-Espinosa L, Montiel-Manriquez R, Castro-Hernandez C, Fragoso-Ontiveros V, Alvarez-Gomez RM, Herrera LA (2020) The promising role of miR-21 as a cancer biomarker and its importance in RNA-based therapeutics. Mol Ther Nucleic Acids 20:409–420. https://doi.org/10.1016/j.omtn.2020.03.003

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Suto T, Yokobori T, Yajima R, Morita H, Fujii T, Yamaguchi S, Altan B, Tsutsumi S, Asao T, Kuwano H (2015) MicroRNA-7 expression in colorectal cancer is associated with poor prognosis and regulates cetuximab sensitivity via EGFR regulation. Carcinogenesis 36:338–345. https://doi.org/10.1093/carcin/bgu242

    Article  CAS  PubMed  Google Scholar 

  81. Zhao J, Wang K, Liao Z, Li Y, Yang H, Chen C, Zhou YA, Tao Y, Guo M, Ren T, Xu L (2015) Promoter mutation of tumor suppressor microRNA-7 is associated with poor prognosis of lung cancer. Mol Clin Oncol 3:1329–1336. https://doi.org/10.3892/mco.2015.648

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Webster RJ, Giles KM, Price KJ, Zhang PM, Mattick JS, Leedman PJ (2009) Regulation of epidermal growth factor receptor signaling in human cancer cells by microRNA-7. J Biol Chem 284:5731–5741. https://doi.org/10.1074/jbc.M804280200

    Article  CAS  PubMed  Google Scholar 

  83. Yang W, Yang X, Wang X, Gu J, Zhou D, Wang Y, Yin B, Guo J, Zhou M (2019) Silencing CDR1as enhances the sensitivity of breast cancer cells to drug resistance by acting as a miR-7 sponge to down-regulate REGgamma. J Cell Mol Med 23:4921–4932. https://doi.org/10.1111/jcmm.14305

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Huang Q, Wu YY, Xing SJ, Yu ZW (2019) Effect of miR-7 on resistance of breast cancer cells to adriamycin via regulating EGFR/PI3K signaling pathway. Eur Rev Med Pharmacol Sci 23:5285–5292. https://doi.org/10.26355/eurrev_201906_18195

    Article  CAS  PubMed  Google Scholar 

  85. Dai X, Chen A, Bai Z (2014) Integrative investigation on breast cancer in ER, PR and HER2-defined subgroups using mRNA and miRNA expression profiling. Sci Rep 4:6566. https://doi.org/10.1038/srep06566

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Kolde R, Laur S, Adler P, Vilo J (2012) Robust rank aggregation for gene list integration and meta-analysis. Bioinformatics 28:573–580. https://doi.org/10.1093/bioinformatics/btr709

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Vosa U, Kolde R, Vilo J, Metspalu A, Annilo T (2014) Comprehensive meta-analysis of microRNA expression using a robust rank aggregation approach. Methods Mol Biol 1182:361–373. https://doi.org/10.1007/978-1-4939-1062-5_28

    Article  CAS  PubMed  Google Scholar 

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Funding

This study was supported by grants from the National Key R&D Program of China (No. 2016YFC0904900), National Science and Technology Major Projects for “Major New Drugs Innovation and Development” (Nos. 2017ZX09101001, 2018ZX09201014 and 2017ZX09304028), National Natural Science Foundation of China (Nos. 81872940, 81973395 and 82073935) and Beijing Natural Science Foundation (No. 7171012).

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  1. Zhuo Zhang and Hanxu Zhang have contributed equally to the article.

Authors and Affiliations

  1. Department of Pharmacy, Peking University First Hospital, Beijing, China

    Zhuo Zhang, Hanxu Zhang, Xiaocong Pang, Qian Xiang, Qianxin Liu & Yimin Cui

  2. School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing, China

    Hanxu Zhang & Yimin Cui

  3. Department of Obstetrics and Gynecology, Peking University First Hospital, Beijing, China

    Jiao Yu

  4. Breast Disease Center, Peking University First Hospital, Beijing, China

    Ling Xu

  5. Institute of Clinical Pharmacology, Peking University, Beijing, China

    Yimin Cui

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  1. Zhuo Zhang
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  4. Ling Xu
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Contributions

ZZ, LX, and YC contributed to the study conception and design. Material preparation, data collection and analysis were performed by ZZ, HZ, JY, and XP. The first draft of the manuscript was written by ZZ and HZ. QX, QL, and YC revised the paper. All authors read and approved the final manuscript.

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Correspondence to Yimin Cui.

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Zhang, Z., Zhang, H., Yu, J. et al. miRNAs as therapeutic predictors and prognostic biomarkers of neoadjuvant chemotherapy in breast cancer: a systematic review and meta-analysis. Breast Cancer Res Treat 194, 483–505 (2022). https://doi.org/10.1007/s10549-022-06642-z

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