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Significant relationship between the LAT1 expression pattern and chemoresistance in ovarian clear cell carcinoma

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Abstract

L-type amino acid transporter 1 (LAT1) is a Na+-independent neutral amino acid transporter that plays a key role in cancer cell growth and survival. To determine the significance of LAT1 in prognosis and resistance to chemotherapy in ovarian carcinoma, we investigated the LAT1 expression in 245 ovarian carcinoma patients by immunohistochemistry using tissue microarray. High expression of LAT1 was detected in 85 (34.7%) patients. The ratio of high expression of LAT1 was significantly high in clear cell carcinoma and low in serous carcinoma compared to other histological types (P < 0.0001). High expression of LAT1 in ovarian carcinoma was associated with poorer prognosis as per log-rank test (P = 0.008). Cox’s univariate and multivariate analysis revealed that high expression of LAT1 is an independent marker indicating poor prognosis (hazard ratio = 2.810, P < 0.0001) as well as the FIGO stage III/IV (vs. I/II) and suboptimal surgery. High LAT1 expression was also found to be associated with resistance to chemotherapy (P = 0.016) notably in clear cell carcinoma. In conclusion, we demonstrate that LAT1 is not only associated with poor prognosis of ovarian carcinoma, but also associated with chemoresistance in ovarian carcinoma.

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Acknowledgments

The authors would appreciate Chinami Onuma for her excellent technical assistance, and Editage (www.editage.jp) for English language editing.

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Authors and Affiliations

  1. Department of Basic Pathology, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama, 359-8513, Japan

    Kimiya Sato & Hitoshi Tsuda

  2. Department of Obstetrics and Gynecology, National Defense Medical College, Tokorozawa, Japan

    Morikazu Miyamoto & Kenichi Furuya

  3. Department of Clinical Oncology, National Defense Medical College, Tokorozawa, Japan

    Masashi Takano

Authors
  1. Kimiya Sato
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  2. Morikazu Miyamoto
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  3. Masashi Takano
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  4. Kenichi Furuya
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  5. Hitoshi Tsuda
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Contributions

Kimiya Sato, Morikazu Miyamoto, Masashi Takano, Kenichi Furuya, and Hitoshi Tsuda conceived and designed the study, and wrote, edited, and reviewed the manuscript. Kimiya Sato and Hitoshi Tsuda researched and analyzed data. All authors gave final approval for publication. Kimiya Sato takes full responsibility for the work as a whole, including the study design, access to data, and the decision to submit and publish the manuscript.

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Correspondence to Kimiya Sato.

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The research protocol was approved by the Institutional Ethical Review Board Committee of the National Defense Medical College, Tokorozawa, Japan. Informed consent was obtained from all the individuals included in this study.

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The authors declare that they have no conflict of interest.

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Sato, K., Miyamoto, M., Takano, M. et al. Significant relationship between the LAT1 expression pattern and chemoresistance in ovarian clear cell carcinoma. Virchows Arch 474, 701–710 (2019). https://doi.org/10.1007/s00428-019-02520-0

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  • DOI: https://doi.org/10.1007/s00428-019-02520-0

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