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. 2024 Mar 15:16:127-139.
doi: 10.2147/BCTT.S445753. eCollection 2024.

ZNF217 Gene Copy Number as a Marker of Response to Standard Therapy Drugs According to ERα Status in Breast Cancer

Nelson Rangel  1 , Iris Lorena Sánchez  2 , Duván Sebastián Valbuena  2 , Milena Rondón-Lagos  2
Affiliations

ZNF217 Gene Copy Number as a Marker of Response to Standard Therapy Drugs According to ERα Status in Breast Cancer

Nelson Rangel et al. Breast Cancer (Dove Med Press). .

Abstract

Purpose: The therapeutic decision for the management of breast cancer (BC) patients is based on the evaluation of prognostic factors alongside clinical and pathological parameters. Despite the use of standard biomarkers, response and resistance to therapy represent a challenge for clinicians. Among the new potential biomarkers for BC the ZNF217 gene have gained importance in recent years. However, while associations between ZNF217 gene copy number and clinicopathological characteristics have been established, its correlation with treatment response remains unclear.

Patients and methods: This study aimed to evaluate the ZNF217 gene copy number and establish its associations with treatment response in estrogen receptor positive (ERα+) and ERα negative (ERα-) BC cell lines. In addition, a validation of the relationship between ZNF217 gene copy number and its prognostic value was performed using datasets of BC patients retrieved from the cBioPortal public database.

Results: Our data show that in ERα+ cells, ZNF217 gene copy number increase (amplification), while cell proliferation decreases in response to standard drug treatments. In contrast, both ZNF217 gene copy number (gain) and cell proliferation increases in response to standard drug treatments in ERα- cells. The results obtained align with findings from the cBioPortal database analysis, demonstrating that ERα+/HER2- low proliferation patients, exhibiting ZNF217 gene amplification or gain, have a significantly higher survival probability after treatment, compared to ERα-/HER2- and HER2+ patients.

Conclusion: Our results suggest that in ERα+ BC cells, ZNF217 gene amplification could be indicative of a favorable response, while in ERα- BC cells, ZNF217 gene gain could be postulated as a potential predictor of treatment resistance. A broader understanding of the role of ZNF217 gene in treatment response, together with prospective studies in BC patients, could contribute to confirming our data, as well as optimizing existing treatments and exploring novel approaches to improve overall cancer treatment outcomes.

Keywords: FISH; chemotherapy; gene amplification; gene gain; hormone therapy; treatment resistance.

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Conflict of interest statement

The authors report no conflicts of interest in this work.

Figures

Figure 1
Figure 1
Effects of single and combined treatments on cell proliferation, and on ZNF217 gene copy number in ERα+ cells after 24h, 48h and 96h. (A and B) MCF7 cells. (C and D) BT474 cells. Error bars represents mean standard deviation of 24 replicates. Differences between control and treatments were evaluated with Dunnett’s multiple comparisons test (see Supplementary Tables 1 and 2).
Figure 2
Figure 2
Representative FISH images of BC cells after TAM treatment for 24h, 48h and 96h. FISH was performed on nuclei spreads for ZNF217 gene and for neighboring regions (20p13) as control, using a dual color probe labeled with different spectrum colors: spectrum orange for ZNF217 gene and spectrum green for 20p13 region. Interphase nuclei at each treatment time point are indicated. The scale bars at the bottom right of each FISH image are indicative of the surface area of the nucleus. Ctrl: Control, untreated cells.
Figure 3
Figure 3
Effects of single and combined treatments on cell proliferation, and on ZNF217 gene copy number in ERα- cells after 24h, 48h and 96h. (A and B) MDA-MB468 cells. (C and D) KPL4 cells. Error bars represents mean standard deviation of 24 replicates. Differences between control and treatments were evaluated with Dunnett’s multiple comparisons test (see Supplementary Tables 3 and 4).
Figure 4
Figure 4
Kaplan–Meier plots of (A) OS and (B) RFS in BC patients with ZNF217 gene amplification or gene gain, versus BC patients without ZNF217 gene amplification or gene gain. (C) Kaplan–Meier plots of RFS in BC patients with ZNF217 gene amplification or (D) ZNF217 gene gain according to molecular subtypes defined by 3 gene classifier model. p value was determined using the Log rank test.
Figure 5
Figure 5
Kaplan–Meier plots of OS or RFS in BC patients with ZNF217 gene amplification or gain according to molecular subtypes defined by 3 gene classifier model and treated with CT or HoT. (A) OS in BC patients with ZNF217 gene amplification treated with HoT. (B) OS in BC patients with ZNF217 gene gain treated with CT. (C) RFS in BC patients with ZNF217 gene gain, treated with HoT. p value was determined using the Log rank test.
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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(3):209–249. doi:10.3322/caac.21660 - DOI - PubMed
    1. Harbeck N, Penault-Llorca F, Cortes J, et al. Breast cancer. Nat Rev Dis Primers. 2019;5(1):66. doi:10.1038/s41572-019-0111-2 - DOI - PubMed
    1. Haibe-Kains B, Desmedt C, Loi S, et al. A three-gene model to robustly identify breast cancer molecular subtypes. JNCI J National Cancer Inst. 2012;104(4):311–325. doi:10.1093/jnci/djr545 - DOI - PMC - PubMed
    1. Gonzalez-Angulo AM, Morales-Vasquez F, Hortobagyi GN. Overview of Resistance to Systemic Therapy in Patients with Breast Cancer. Madame curie bioscience database. Available from: https://www.ncbi.nlm.nih.gov/books/NBK6306/. Accessed October 17, 2023. - PubMed
    1. Szostakowska M, Trębińska-Stryjewska A, Grzybowska EA, Fabisiewicz A. Resistance to endocrine therapy in breast cancer: molecular mechanisms and future goals. Breast Cancer Res Treat. 2019;173(3):489–497. doi:10.1007/s10549-018-5023-4 - DOI - PMC - PubMed

Grants and funding

This work was supported by Universidad Pedagógica y Tecnológica de Colombia and by Pontificia Universidad Javeriana through the “Support for the publication of high-quality research articles 2024” grant.
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