The Correlation Study Between TOP2A Gene Expression in Circulating Tumor Cells and Chemotherapeutic Drug Resistance of Patients with Breast Cancer

Overview

Journal Breast Cancer

Specialty Oncology

Date 2024 Apr 1

PMID 38561479

Authors

Jin-Hui Ye

Jian Yu

Ming-Ying Huang

Yue-Mei Mo

Affiliations

Soon will be listed here.

Abstract

Background: Patients with breast cancer (BC) at advanced stages have poor outcomes because of high rate of recurrence and metastasis. Biomarkers for predicting prognosis remain to be explored. This study aimed to evaluate the relationships between circulating tumor cells (CTCs) and outcomes of BC patients.

Patients And Methods: A total of 50 female were enrolled in this study. Their diagnoses were determined by clinical characteristics, image data, and clinical pathology. CTC subtypes and TOP2A gene expression on CTCs were detected by CanPatrol™ technology and triple color in situ RNA hybridization (RNA-ISH), which divided into epithelial CTCs (eCTCs), mesenchymal CTCs (MCTCs), and hybrid CTCs (HCTCs) based on their surface markers. Hormone receptor, including estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER-2) expression, was measured by immunohistochemistry (IHC) method before treatment. The risk factors for predicting recurrence and metastasis were calculated by COX risk regression model. The progression-free survival (PFS) of patients was determined using Kaplan-Meier survival curve.

Results: The patients with a large tumor size (≥ 3 cm) and advanced tumor node metastasis (TNM) stages had high total CTCs (TCTCs) (P < 0.05). These patients also had high TOP2A expression level. COX risk regression analysis indicated that TOP2A expression levels in TCTCs, ER + , HER-2 + , and TNM stages were critical risk factors for recurrence and metastasis of patients (P < 0.05). The PFS of patients with ≥ 5 TCTCs, ≥ 3 HCTCs, and positive TOP2A expression in ≥ 3 TCTCs was significantly longer than that in patient with < 5 TCTCs, < 3 HCTCs, and TOP2A expression in < 3 TCTCs (P < 0.05). In contrast, the PFS of patients with positive hormone receptors (ER + , PR + , HER-2 +) also was dramatically lived longer than that in patients with negative hormone receptor expression.

Conclusions: High TCTC, HCTCs, and positive TOP2A gene expression on CTCs were critical biomarkers for predicting outcomes of BC patients. Positive hormone receptor expression in BC patients has significant favor PFS.

Citing Articles

Disrupted Lipid Metabolism, Cytokine Signaling, and Dormancy: Hallmarks of Doxorubicin-Resistant Triple-Negative Breast Cancer Models.

Vishnubalaji R, Alajez N Cancers (Basel). 2025; 16(24.

PMID: 39766172 PMC: 11674486. DOI: 10.3390/cancers16244273.

Prognostic model based on tumor stemness genes for triple-negative breast cancer.

Ouyang M, Gui Y, Li N, Zhao L Sci Rep. 2024; 14(1):30855.

PMID: 39730613 PMC: 11680876. DOI: 10.1038/s41598-024-81503-x.

References

Balasubramanian R, Rolph R, Morgan C, Hamed H . Genetics of breast cancer: management strategies and risk-reducing surgery. Br J Hosp Med (Lond). 2019; 80(12):720-725. DOI: 10.12968/hmed.2019.80.12.720. View

Siegel R, Miller K, Jemal A . Cancer statistics, 2020. CA Cancer J Clin. 2020; 70(1):7-30. DOI: 10.3322/caac.21590. View

Bray F, Ferlay J, Laversanne M, Brewster D, Gombe Mbalawa C, Kohler B . Cancer Incidence in Five Continents: Inclusion criteria, highlights from Volume X and the global status of cancer registration. Int J Cancer. 2015; 137(9):2060-71. DOI: 10.1002/ijc.29670. View

Gage M, Wattendorf D, Henry L . Translational advances regarding hereditary breast cancer syndromes. J Surg Oncol. 2012; 105(5):444-51. DOI: 10.1002/jso.21856. View

Leite A, Macedo A, Lagoeiro Jorge A, Martins W . Antiplatelet Therapy in Breast Cancer Patients Using Hormonal Therapy: Myths, Evidence and Potentialities - Systematic Review. Arq Bras Cardiol. 2018; 111(2):205-212. PMC: 6122903. DOI: 10.5935/abc.20180138. View

Burstein H, Temin S, Anderson H, Buchholz T, Davidson N, Gelmon K . Adjuvant endocrine therapy for women with hormone receptor-positive breast cancer: american society of clinical oncology clinical practice guideline focused update. J Clin Oncol. 2014; 32(21):2255-69. PMC: 4876310. DOI: 10.1200/JCO.2013.54.2258. View

Jahanzeb M . Adjuvant trastuzumab therapy for HER2-positive breast cancer. Clin Breast Cancer. 2008; 8(4):324-33. DOI: 10.3816/CBC.2008.n.037. View

Burgess D, Doles J, Zender L, Xue W, Ma B, McCombie W . Topoisomerase levels determine chemotherapy response in vitro and in vivo. Proc Natl Acad Sci U S A. 2008; 105(26):9053-8. PMC: 2435590. DOI: 10.1073/pnas.0803513105. View

Mano M, Rosa D, de Azambuja E, Ismael G, Durbecq V . The 17q12-q21 amplicon: Her2 and topoisomerase-IIalpha and their importance to the biology of solid tumours. Cancer Treat Rev. 2006; 33(1):64-77. DOI: 10.1016/j.ctrv.2006.10.001. View

10.

de Lucio B, Manuel V, Barrera-Rodriguez R . Characterization of human NSCLC cell line with innate etoposide-resistance mediated by cytoplasmic localization of topoisomerase II alpha. Cancer Sci. 2005; 96(11):774-83. PMC: 11158927. DOI: 10.1111/j.1349-7006.2005.00111.x. View

11.

Yu M, Bardia A, Wittner B, Stott S, Smas M, Ting D . Circulating breast tumor cells exhibit dynamic changes in epithelial and mesenchymal composition. Science. 2013; 339(6119):580-4. PMC: 3760262. DOI: 10.1126/science.1228522. View

12.

Ricordel C, Chaillot L, Vlachavas E, Logotheti M, Jouannic A, Desvallees T . Genomic characteristics and clinical significance of CD56+ circulating tumor cells in small cell lung cancer. Sci Rep. 2023; 13(1):3626. PMC: 9984363. DOI: 10.1038/s41598-023-30536-9. View

13.

Kalluri R, Weinberg R . The basics of epithelial-mesenchymal transition. J Clin Invest. 2009; 119(6):1420-8. PMC: 2689101. DOI: 10.1172/JCI39104. View

14.

Thiery J, Acloque H, Huang R, Nieto M . Epithelial-mesenchymal transitions in development and disease. Cell. 2009; 139(5):871-90. DOI: 10.1016/j.cell.2009.11.007. View

15.

Yang J, Ma J, Jin Y, Cheng S, Huang S, Zhang N . Development and validation for prognostic nomogram of epithelial ovarian cancer recurrence based on circulating tumor cells and epithelial-mesenchymal transition. Sci Rep. 2021; 11(1):6540. PMC: 7985206. DOI: 10.1038/s41598-021-86122-4. View

16.

Gao T, Mao J, Huang J, Luo F, Lin L, Lian Y . Prognostic significance of circulating tumor cell measurement in the peripheral blood of patients with nasopharyngeal carcinoma. Clinics (Sao Paulo). 2023; 78:100179. PMC: 10064788. DOI: 10.1016/j.clinsp.2023.100179. View

17.

Li J, Liao Y, Ran Y, Wang G, Wu W, Qiu Y . Evaluation of sensitivity and specificity of CanPatrol™ technology for detection of circulating tumor cells in patients with non-small cell lung cancer. BMC Pulm Med. 2020; 20(1):274. PMC: 7576719. DOI: 10.1186/s12890-020-01314-4. View

18.

Wolff A, Hammond M, Allison K, Harvey B, Mangu P, Bartlett J . 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. DOI: 10.1200/JCO.2018.77.8738. View

19.

Joseph C, Papadaki A, Althobiti M, Alsaleem M, Aleskandarany M, Rakha E . Breast cancer intratumour heterogeneity: current status and clinical implications. Histopathology. 2018; 73(5):717-731. DOI: 10.1111/his.13642. View

20.

Li Y, Jiang X, Zhong M, Yu B, Yuan H . Whole Genome Sequencing of Single-Circulating Tumor Cell Ameliorates Unraveling Breast Cancer Heterogeneity. Breast Cancer (Dove Med Press). 2023; 14:505-513. PMC: 9805725. DOI: 10.2147/BCTT.S388653. View