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Overexpression of Stat3 increases circulating cfDNA in breast cancer

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Abstract

Purpose

Current studies on circulating cell-free DNA (cfDNA) have been focusing on its potential as biomarkers in liquid biopsy by detecting its content or genetic and epigenetic changes for the evaluation of tumor burden and therapeutic efficacy. However, the regulatory mechanism of cfDNA release remains unclear. Stat3 has been documented as an oncogene for the development and metastasis of breast cancer cells. In this study, we investigated whether Stat3 affects the release of cfDNA into blood and its association with the number of circulating tumor cells (CTCs).

Methods

The cfDNA level in plasma of patients with breast cancer and healthy volunteers were determined by quantitative real-time PCR. Three mouse breast cancer models with different Stat3 expression were generated and used to established three breast cancer orthotopic animal models to examine the effect of Stat3 on cfDNA release in vivo. Stat3 mediated Epithelial-mesenchymal phenotype transition of CTCs was determined by immunofluorescence assay and Western blot assay.

Results

The data showed that Stat3 increased circulating cfDNA, which is correlated with the increased volume of primary tumors and number of CTCs, accompanied with the dynamic EMT changes regulated by Snail induction. Furthermore, the high level of total circulating cfDNA and Stat3-cfDNA in patients with breast cancer were detected by quantitative real-time PCR using GAPDH and Stat3 primers.

Conclusion

Our results suggested that Stat3 increases the circulating cfDNA and CTCs in breast cancer.

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Acknowledgements

The present study was supported by the National Natural Science Foundation of China (No. 81472489), Shandong Co-Innovation Center of Classic TCM formula (2019KF203), Shandong University of Traditional Chinese Medicine.

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Authors and Affiliations

  1. Laboratory of Molecular Oncology, Weifang Medical College, Weifang, 261053, Shandong, China

    Yi-Fei Wang, Xue-Jian Wang, Zhong Lu, Shu-Rong Liu, Yu Jiang, Xiao-Qing Wan, Cong-Cong Cheng, Li-Hong Shi, Li-Hua Wang & Yi Ding

  2. Affiliated Hospital, Weifang Medical University, Weifang, 261053, Shandong, China

    Yi-Fei Wang, Zhong Lu, Shu-Rong Liu, Yu Jiang, Cong-Cong Cheng & Li-Hua Wang

  3. Key Laboratory of Applied Pharmacology, Weifang Medical University, Weifang, 261053, Shandong, China

    Xue-Jian Wang, Li-Hong Shi & Yi Ding

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  1. Yi-Fei Wang
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  2. Xue-Jian Wang
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Correspondence to Yi Ding.

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Conflict of interest

The authors declare that they have no competing interests. The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

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All procedures performed involving human participants were in accordance with the ethical standards of the institutional research committee, and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. All applicable international guidelines for the care and use of animals were followed.

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Informed consent was obtained from all individual participants included in the study. The present study was reviewed and approved by the Ethics Committee of the Weifang Medical University. The animal study was approved by the Ethics Committee of Weifang Medical University.

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Wang, YF., Wang, XJ., Lu, Z. et al. Overexpression of Stat3 increases circulating cfDNA in breast cancer. Breast Cancer Res Treat 187, 69–80 (2021). https://doi.org/10.1007/s10549-021-06142-6

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