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High expression of TIMP-1 in human breast cancer tissues is a predictive of resistance to paclitaxel-based chemotherapy

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Abstract

For breast cancer patients with lymph node metastasis, paclitaxel is the first-line chemotherapy drug. Clinical studies showed that some patients with breast cancer were insensitive to paclitaxel, which led to chemotherapy failure. Today, no validated markers exist for the prediction of chemotherapy sensitivity in this patient group. Tissue inhibitor of metalloproteinases-1 (TIMP-1) has been shown to protect against apoptosis. Epidemiological studies have also associated elevated tumor tissue TIMP-1 levels with a poor response to cyclophosphamide/methotrexate/5-fluorouracil and anthracycline-based chemotherapy. Additionally, our previous study proved that TIMP-1 significantly decreased the sensitivity of breast cancer cells to paclitaxel-induced apoptosis by enhancing degradation of cyclin B1. These data imply that TIMP-1 may be a useful predictive biomarker for chemotherapy resistance. In this retrospective study, we investigated the association between expression levels of TIMP-1 protein in the primary tumor and objective response to paclitaxel-based chemotherapy in 99 patients with breast cancer. With Kaplan–Meier survival analysis, the patients with high TIMP-1 levels were found to have significantly worse 5-year DFS (71.1 %) than the patients with low levels (88.5 %; P = 0.020). Similarly, the patients with high TIMP-1 levels had significantly worse 5-year OS (78.9 %) than patients with low levels (96.7 %; P = 0.004). In Cox’s univariate and multivariate analyses, TIMP-1 was prognostic for both DFS and OS. Our data showed that elevated tumor tissue TIMP-1 levels were significantly associated with a poor response to paclitaxel-based chemotherapy, and TIMP-1 might be a potential biomarker for predicting response of breast cancer patients to paclitaxel-based chemotherapy.

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Acknowledgments

This work was supported by The National Natural Science Foundation of China (Grant 30870978). We have read and have abided by the statement of ethical standards laid down in the 1964 Declaration of Helsinki.

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Authors and Affiliations

  1. Key Laboratory of Human Functional Genomics of Jiangsu Province, Nanjing Medical University, Nanjing, 210029, People’s Republic of China

    Dongliang Zhu, Meiling Hu & Yujie Sun

  2. Department of Cell Biology, Nanjing Medical University, Nanjing, 210029, People’s Republic of China

    Dongliang Zhu & Yujie Sun

  3. Department of General Surgery, The First Affiliated Hospital with Nanjing Medical University, Nanjing, 210029, People’s Republic of China

    Xiaoming Zha & Aidi Tao

  4. Department of Pathology, Nanjing General Hospital of Nanjing Military Command, Nanjing, 210016, People’s Republic of China

    Hangbo Zhou & Xiaojun Zhou

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  1. Dongliang Zhu
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  2. Xiaoming Zha
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  3. Meiling Hu
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  4. Aidi Tao
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  5. Hangbo Zhou
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Correspondence to Yujie Sun.

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Zhu, D., Zha, X., Hu, M. et al. High expression of TIMP-1 in human breast cancer tissues is a predictive of resistance to paclitaxel-based chemotherapy. Med Oncol 29, 3207–3215 (2012). https://doi.org/10.1007/s12032-012-0239-3

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  • DOI: https://doi.org/10.1007/s12032-012-0239-3

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