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KRT19 and CEACAM5 mRNA-marked circulated tumor cells indicate unfavorable prognosis of breast cancer patients

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Breast Cancer Research and Treatment Aims and scope Submit manuscript

Abstract

Aim

To investigate the clinical and prognostic significance of circulated tumor cells (CTC) marked by cytokeratin 19 coding gene KRT19 mRNA and carcinoembryonic antigen coding gene CEACAM5 mRNA in preoperative peripheral blood of breast cancer patients and provide molecular markers for breast cancer metastasis risk.

Methods

The mRNA levels of KRT19 and CEACAM5 in preoperative peripheral blood of breast cancer patients without (n = 603) and with (n = 76) distant metastases at the time of initial diagnosis were detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The relationship between CTCKRT19, CTCCEACAM5 and clinicopathological features, local recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), or overall survival (OS) was statistically analyzed.

Results

In different pathological stages of breast cancer, the rates of CTCKRT19−pos and CTCCEACAM5−pos increased with the increase of the stages (P = 0.077 and P = 0.004). Preoperative CTCKRT19−pos in breast cancer patients was closely related to the lymph node metastasis statues (P < 0.0001), and had no significant correlation with other clinicopathological features. There was no significant correlation between CTCCEACAM5 and the clinicopathological features. Patients with high levels of CTC double-marked by KRT19 and CEACAM5 mRNA had shorter DMFS (P < 0.0001) and OS (P = 0.016) for patients with breast cancer. The 7-year DMFS rates for the low-, intermediate-, and high-risk groups were 90.7%, 67.5%, and 59.1%, respectively (P < 0.0001). The prognosis of patients with decreased KRT19 and CEACAM5 mRNA after treatment is better than that of patients who have not decreased, and the combination of the two indicators is better than the single one for predicting PFS (P = 0.002 compare with P = 0.036 or P = 0.047).

Conclusion

Double-marked CTC by KRT19 and CEACAM5 mRNA is a prognostic index of breast cancer patients before surgery and after chemotherapy. Single-marked CTC by KRT19 mRNA indicates lymph node statues of preoperative patients. Therefore, the RT-qPCR-based molecular diagnosis of CTC could be used for prognostic prediction of breast cancer patients and guiding clinical treatment.

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Acknowledgements

The authors would like to thank Dr. Yumei Feng (Tianjin Medical University Cancer Research Institute and Hospital Department of Biochemistry and Molecular Biology, Tianjin, China) for the useful discussion and insightful observation during the research process. Thanks to Tianjin Medical University Cancer Research Institute and Hospital laboratory of Biochemistry and Molecular Biology for technical assistance in RT-qPCR.

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Authors and Affiliations

  1. First Department of Breast Cancer, National Clinical Research Center of Cancer, Tianjin Medical University Cancer Institute and Hospital, 1 Huan-Hu Xi Road, Ti-Yuan Bei, He Xi, Tianjin, 300060, People’s Republic of China

    Xi-Mei Wang, Zhen Zhang, Li-Hui Pan, Xu-Chen Cao & Chunhua Xiao

  2. Key Laboratory of Cancer Prevention and Therapy, Tianjin, People’s Republic of China

    Xi-Mei Wang, Zhen Zhang, Li-Hui Pan, Xu-Chen Cao & Chunhua Xiao

  3. Key Laboratory of Breast Cancer Prevention and Therapy, Ministry of Education, Tianjin Medical University, Tianjin, 300060, People’s Republic of China

    Xi-Mei Wang, Zhen Zhang, Li-Hui Pan, Xu-Chen Cao & Chunhua Xiao

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  1. Xi-Mei Wang
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Correspondence to Chunhua Xiao.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the respective institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. This article does not contain any studies with animals performed by any of the authors.

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Informed consent was obtained from all individual participants included in the study.

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Wang, XM., Zhang, Z., Pan, LH. et al. KRT19 and CEACAM5 mRNA-marked circulated tumor cells indicate unfavorable prognosis of breast cancer patients. Breast Cancer Res Treat 174, 375–385 (2019). https://doi.org/10.1007/s10549-018-05069-9

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  • DOI: https://doi.org/10.1007/s10549-018-05069-9

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