CC BY-NC-ND 4.0 · J Lab Physicians
DOI: 10.1055/s-0043-1774405
Original Article

Unrevealing the Role of miRNA in Successful TNBC Treatment: A Pilot Study to Explore the Chemotherapy Drugs for Timely Treatment of TNBC

Poulami Sarkar*
1   Department of Biochemistry, All India Institute of Medical Sciences (AIIMS), Bhopal, Madhya Pradesh, India
,
Rashmi Chowdhary*
1   Department of Biochemistry, All India Institute of Medical Sciences (AIIMS), Bhopal, Madhya Pradesh, India
,
Ashish Kumar Yadav
1   Department of Biochemistry, All India Institute of Medical Sciences (AIIMS), Bhopal, Madhya Pradesh, India
,
Neha Arya
2   Department of Translational Medicine, All India Institute of Medical Sciences (AIIMS), Bhopal, Madhya Pradesh, India
,
Bharti Pandya
3   Department of Surgery, All India Institute of Medical Sciences (AIIMS), Bhopal, Madhya Pradesh, India
,
Vinay Kumar
4   Department of Surgical Oncology, All India Institute of Medical Sciences (AIIMS), Bhopal, Madhya Pradesh, India
,
Jagat R. Kanwar
1   Department of Biochemistry, All India Institute of Medical Sciences (AIIMS), Bhopal, Madhya Pradesh, India
,
Arshi Siddiqui
5   Department of Biotechnology, Barkatullah University, Bhopal, Madhya Pradesh, India
,
Roji Begum Khan
6   School of Biotechnology, Rajiv Gandhi Proudyogiki Vishwavidyalaya (RGPV), Bhopal, Madhya Pradesh, India
› Author Affiliations
Funding None.

Abstract

Objective Worldwide, breast cancer is the most prevalent and common type of cancer. Physical examination and mammography with a range of sensitivities are currently used as screening methods. Triple-negative breast cancer (TNBC) lacks estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER-2) gene expression. MicroRNAs (miRNA) as potential prognostic and diagnostic biomarkers, miRNA 125, 200c, 221, 21, and 34a were selected for study.

Materials and Methods Here, 25 consenting TNBC patients with negative ER/PR/HER-2 status and compatible history were accrued from the Department of Oncosurgery, All India Institutes of Medical Sciences (AIIMS) Bhopal. Serum from participants and 25 controls was collected for quantitative estimation of miRNA by quantitative real-time polymerase chain reaction. After being treated with epirubicin, capecitabine, and paclitaxel, the MDA-MB-231 cell line's expression of these miRNA subtypes was also examined.

Results miRNA125 (p< 0.0001) and miRNA21 (p< 0.05) were found to be statistically significant. miR125 (ΔCt [cycle threshold] 2.77) was seen to be upregulated and miR21 (ΔCt -1.61) was seen to be downregulated in TNBC patients. Epirubicin treatment caused miR125 to be downregulated, but capecitabine treatment caused miR125 to be upregulated. Paclitaxel was seen to downregulate miR21. All three chemotherapeutic agents were seen to downregulate miR34a.

Conclusion miRNAs can be developed into a reliable biomarker and prognostic tool with more research. They can also help develop and improve pharmaco-therapeutic strategies.

Declaration

I guarantee this is my original work, and I have the rights in the work. I am submitting the work for first publication in this journal and it is not being considered for publication elsewhere. It has not already been published elsewhere, and I have obtained and can supply all necessary permissions for the reproduction of any copyright works not owned by you.


Ethical Approval

Ref No.-IHEC-LOP/2019/EF0111 by, Institutional Human Ethics Committee, All India Institute of Medical Sciences (AIIMS) Bhopal, Madhya Pradesh, India.


* Poulami Sarkar and Dr Rashmi Chowdhary are first and Joint authors in this study.


Supplementary Material



Publication History

Received: 24 April 2023

Accepted: 09 August 2023

Article published online:
05 September 2023

© 2023. The Indian Association of Laboratory Physicians. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/)

Thieme Medical and Scientific Publishers Pvt. Ltd.
A-12, 2nd Floor, Sector 2, Noida-201301 UP, India

 
  • References

  • 1 Sung H, Ferlay J, Siegel RL. et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin 2021; 71 (03) 209-249
  • 2 Drukteinis JS, Mooney BP, Flowers CI, Gatenby RA. Beyond mammography: new frontiers in breast cancer screening. Am J Med 2013; 126 (06) 472-479
  • 3 Wolff AC, Hammond MEH, Allison KH. et al. Human epidermal growth factor receptor 2 testing in breast cancer: American Society of Clinical Oncology/College of American Pathologists Clinical Practice Guideline Focused Update. J Clin Oncol 2018; 36 (20) 2105-2122
  • 4 Prat A, Perou CM. Deconstructing the molecular portraits of breast cancer. Mol Oncol 2011; 5 (01) 5-23
  • 5 Cortazar P, Zhang L, Untch M. et al. Pathological complete response and long-term clinical benefit in breast cancer: the CTNeoBC pooled analysis. Lancet 2014; 384 (9938) 164-172
  • 6 McLaughlin SA. Surgical management of the breast: breast conservation therapy and mastectomy. Surg Clin North Am 2013; 93 (02) 411-428
  • 7 Survival Study of Triple-Negative and Non–Triple-Negative Breast Cancer in a Brazilian Cohort - Homero Gonçalves, Maximiliano Ribeiro Guerra, Jane Rocha Duarte Cintra, Vívian Assis Fayer, Igor Vilela Brum, Maria Teresa Bustamante Teixeira, 2018 [Internet]. [cited 2021 Jul 26]. Accessed August 25, 2023: https://journals.sagepub.com/doi/full/10.1177/1179554918790563
  • 8 Cardoso F, Harbeck N, Barrios CH. et al. Research needs in breast cancer. Ann Oncol 2017; 28 (02) 208-217
  • 9 Malla RR, Kumari S, Gavara MM. et al. A perspective on the diagnostics, prognostics, and therapeutics of microRNAs of triple-negative breast cancer. Biophys Rev 2019; 11 (02) 227-234
  • 10 McAnena P, Lowery A, Kerin MJ. Role of micro-RNAs in breast cancer surgery. Br J Surg 2018; 105 (02) e19-e30
  • 11 Reddy KB. MicroRNA (miRNA) in cancer. Cancer Cell Int 2015; 15 (01) 38
  • 12 Wang Z, Li Y, Ahmad A. et al. Targeting miRNAs involved in cancer stem cell and EMT regulation: an emerging concept in overcoming drug resistance. Drug Resist Updat 2010; 13 (4-5): 109-118
  • 13 Ma J, Dong C, Ji C. MicroRNA and drug resistance. Cancer Gene Ther 2010; 17 (08) 523-531
  • 14 Zhang L, Liao Y, Tang L. MicroRNA-34 family: a potential tumor suppressor and therapeutic candidate in cancer. J Exp Clin Cancer Res 2019; 38 (01) 53
  • 15 Li ZH, Weng X, Xiong QY. et al. miR-34a expression in human breast cancer is associated with drug resistance. Oncotarget 2017; 8 (63) 106270-106282
  • 16 Banzhaf-Strathmann J, Edbauer D. Good guy or bad guy: the opposing roles of microRNA 125b in cancer. Cell Commun Signal 2014; 12 (01) 30
  • 17 Yang Z, Liu Z. The emerging role of microRNAs in breast cancer. J Oncol 2020; 2020: 9160905
  • 18 Vilquin P, Donini CF, Villedieu M. et al. MicroRNA-125b upregulation confers aromatase inhibitor resistance and is a novel marker of poor prognosis in breast cancer. Breast Cancer Res 2015; 17 (01) 13
  • 19 Najjary S, Mohammadzadeh R, Mokhtarzadeh A, Mohammadi A, Kojabad AB, Baradaran B. Role of miR-21 as an authentic oncogene in mediating drug resistance in breast cancer. Gene 2020; 738: 144453 DOI: 10.1016/j.gene.2020.144453.
  • 20 Wang H, Tan Z, Hu H. et al. microRNA-21 promotes breast cancer proliferation and metastasis by targeting LZTFL1. BMC Cancer 2019; 19 (01) 738
  • 21 Song Q, An Q, Niu B, Lu X, Zhang N, Cao X. Role of miR-221/222 in tumor development and the underlying mechanism. J Oncol 2019; 2019: 7252013
  • 22 Klicka K, Grzywa TM, Mielniczuk A, Klinke A, Włodarski PK. The role of miR-200 family in the regulation of hallmarks of cancer. Front Oncol 2022; 12: 965231 https://www.frontiersin.org/articles/10.3389/fonc.2022.965231
  • 23 Le MT, Hamar P, Guo C. et al. miR-200-containing extracellular vesicles promote breast cancer cell metastasis. J Clin Invest 2014; 124 (12) 5109-5128
  • 24 Thi Chung Duong T, Nguyen THN, Thi Ngoc Nguyen T, Huynh LH, Ngo HP, Thi Nguyen H. Diagnostic and prognostic value of miR-200 family in breast cancer: A meta-analysis and systematic review. Cancer Epidemiol 2022; 77: 102097
  • 25 Cancer Staging System [Internet]. American College of Surgeons. [cited 2021 Jul 29]. Accessed August 25, 2023: http://www.facs.org/quality-programs/cancer/ajcc/cancer-staging
  • 26 Saha. Clinical Cancer Investigation Journal [Internet]. [cited 2021 Jul 24]. Accessed August 25, 2023: https://www.ccij-online.org/article.asp?issn=2278-0513;year=2012;volume=1;issue=4;spage=201;epage=205;aulast=Saha
  • 27 Akhtar M, Dasgupta S, Rangwala M. Triple negative breast cancer: an Indian perspective. Breast Cancer (Dove Med Press) 2015; 7: 239-243
  • 28 Tariq K, Farhangi A, Rana F. TNBC vs non-TNBC: a retrospective review of differences in mean age, family history, smoking history, and stage at diagnosis. Clin Adv Hematol Oncol 2014; 12 (06) 377-381
  • 29 Malvia S, Bagadi SA, Dubey US, Saxena S. Epidemiology of breast cancer in Indian women. Asia Pac J Clin Oncol 2017; 13 (04) 289-295
  • 30 Lakshmaiah KC, Das U, Suresh TM. et al. A study of triple negative breast cancer at a tertiary cancer care center in southern India. Ann Med Health Sci Res 2014; 4 (06) 933-937
  • 31 Suba Z. Triple-negative breast cancer risk in women is defined by the defect of estrogen signaling: preventive and therapeutic implications. OncoTargets Ther 2014; 7: 147-164
  • 32 Phipps AI, Buist DS, Malone KE. et al. Family history of breast cancer in first-degree relatives and triple-negative breast cancer risk. Breast Cancer Res Treat 2011; 126 (03) 671-678
  • 33 Brewer HR, Jones ME, Schoemaker MJ, Ashworth A, Swerdlow AJ. Family history and risk of breast cancer: an analysis accounting for family structure. Breast Cancer Res Treat 2017; 165 (01) 193-200
  • 34 Nabi MG, Ahangar A, Wahid MA, Kuchay S. Clinicopathological comparison of triple negative breast cancers with non-triple negative breast cancers in a hospital in North India. Niger J Clin Pract 2015; 18 (03) 381-386
  • 35 Perkins CI, Hotes J, Kohler BA, Howe HL. Association between breast cancer laterality and tumor location, United States, 1994-1998. Cancer Causes Control 2004; 15 (07) 637-645
  • 36 Garfinkel L, Craig L, Seidman H. An appraisal of left and right breast cancer. J Natl Cancer Inst 1959; 23: 617-631
  • 37 Anderson K, Thompson PA, Wertheim BC. et al. Family history of breast and ovarian cancer and triple negative subtype in Hispanic/Latina women. Springerplus 2014; 3: 727
  • 38 Agarwal G, Ramakant P. Breast cancer care in India: the current scenario and the challenges for the future. Breast Care (Basel) 2008; 3 (01) 21-27
  • 39 Cornier MA, Dabelea D, Hernandez TL. et al. The metabolic syndrome. Endocr Rev 2008; 29 (07) 777-822
  • 40 Davis AA, Kaklamani VG. Metabolic syndrome and triple-negative breast cancer: a new paradigm. Int J Breast Cancer 2012; 2012: 809291
  • 41 Guo LJ, Zhang QY. Decreased serum miR-181a is a potential new tool for breast cancer screening. Int J Mol Med 2012; 30 (03) 680-686
  • 42 Maiti B, Kundranda MN, Spiro TP, Daw HA. The association of metabolic syndrome with triple-negative breast cancer. Breast Cancer Res Treat 2010; 121 (02) 479-483
  • 43 Cleveland RJ, Eng SM, Abrahamson PE. et al. Weight gain prior to diagnosis and survival from breast cancer. Cancer Epidemiol Biomarkers Prev 2007; 16 (09) 1803-1811
  • 44 Sun H, Zou J, Chen L, Zu X, Wen G, Zhong J. Triple-negative breast cancer and its association with obesity. Mol Clin Oncol 2017; 7 (06) 935-942
  • 45 Benefield HC, Zirpoli GR, Allott EH. et al. Epidemiology of basal-like and luminal breast cancers among black women in the AMBER Consortium. Cancer Epidemiol Biomarkers Prev 2021; 30 (01) 71-79 DOI: 10.1158/1055-9965.EPI-20-0556.
  • 46 Hsieh CC, Trichopoulos D. Breast size, handedness and breast cancer risk. Eur J Cancer 1991; 27 (02) 131-135
  • 47 Al-Mahmood S, Sapiezynski J, Garbuzenko OB, Minko T. Metastatic and triple-negative breast cancer: challenges and treatment options. Drug Deliv Transl Res 2018; 8 (05) 1483-1507
  • 48 Lv Y, Ma X, Du Y, Feng J. Understanding patterns of brain metastasis in triple-negative breast cancer and exploring potential therapeutic targets. OncoTargets Ther 2021; 14: 589-607
  • 49 Cuk K, Zucknick M, Heil J. et al. Circulating microRNAs in plasma as early detection markers for breast cancer. Int J Cancer 2013; 132 (07) 1602-1612
  • 50 Wang JK, Wang Z, Li G. MicroRNA-125 in immunity and cancer. Cancer Lett 2019; 454: 134-145
  • 51 Nie J, Jiang HC, Zhou YC. et al. MiR-125b regulates the proliferation and metastasis of triple negative breast cancer cells via the Wnt/β-catenin pathway and EMT. Biosci Biotechnol Biochem 2019; 83 (06) 1062-1071
  • 52 Dong G, Liang X, Wang D. et al. High expression of miR-21 in triple-negative breast cancers was correlated with a poor prognosis and promoted tumor cell in vitro proliferation. Med Oncol 2014; 31 (07) 57
  • 53 Garofalo M, Quintavalle C, Romano G, Croce CM, Condorelli G. miR221/222 in cancer: their role in tumor progression and response to therapy. Curr Mol Med 2012; 12 (01) 27-33
  • 54 Chen H, Li Z, Zhang L. et al. MicroRNA-200c inhibits the metastasis of triple-negative breast cancer by targeting ZEB2, an epithelial-mesenchymal transition regulator. Ann Clin Lab Sci 2020; 50 (04) 519-527
  • 55 Zeng Z, Chen X, Zhu D, Luo Z, Yang M. Low expression of circulating MicroRNA-34c is associated with poor prognosis in triple-negative breast cancer. Yonsei Med J 2017; 58 (04) 697-702
  • 56 Fang H, Xie J, Zhang M, Zhao Z, Wan Y, Yao Y. miRNA-21 promotes proliferation and invasion of triple-negative breast cancer cells through targeting PTEN. Am J Transl Res 2017; 9 (03) 953-961
  • 57 Isakoff SJ. Triple-negative breast cancer: role of specific chemotherapy agents. Cancer J 2010; 16 (01) 53-61
  • 58 Wein L, Loi S. Mechanisms of resistance of chemotherapy in early-stage triple negative breast cancer (TNBC). Breast 2017; 34 (Suppl. 01) S27-S30
  • 59 Jin J, Zhang W, Ji W, Yang F, Guan X. Predictive biomarkers for triple negative breast cancer treated with platinum-based chemotherapy. Cancer Biol Ther 2017; 18 (06) 369-378
  • 60 Ourô S, Mourato C, Velho S. et al. Potential of miR-21 to predict incomplete response to chemoradiotherapy in rectal adenocarcinoma. Front Oncol 2020; 10: 577653
  • 61 Wang H, Tan G, Dong L. et al. Circulating MiR-125b as a marker predicting chemoresistance in breast cancer. PLoS One 2012; 7 (04) e34210
  • 62 Sandhu GS, Erqou S, Patterson H, Mathew A. Prevalence of triple-negative breast cancer in India: systematic review and meta-analysis. J Glob Oncol 2016; 2 (06) 412-421
  • 63 Thakur KK, Bordoloi D, Kunnumakkara AB. Alarming burden of triple-negative breast cancer in India. Clin Breast Cancer 2018; 18 (03) e393-e399
  • 64 Mehanna J, Haddad FG, Eid R, Lambertini M, Kourie HR. Triple-negative breast cancer: current perspective on the evolving therapeutic landscape. Int J Womens Health 2019; 11: 431-437
  • 65 Dass SA, Tan KL, Selva Rajan R. et al. Triple negative breast cancer: a review of present and future diagnostic modalities. Medicina (Kaunas) 2021; 57 (01) 62