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High levels of human epididymis protein 4 mRNA and protein expression are associated with chemoresistance and a poor prognosis in pancreatic cancer

  • Authors:
    • Ryotaro Ohkuma
    • Erica Yada
    • Shumpei Ishikawa
    • Daisuke Komura
    • Yutaro Kubota
    • Kazuyuki Hamada
    • Atsushi Horiike
    • Tomoyuki Ishiguro
    • Yuya Hirasawa
    • Hirotsugu Ariizumi
    • Midori Shida
    • Makoto Watanabe
    • Rie Onoue
    • Kiyohiro Ando
    • Junji Tsurutani
    • Kiyoshi Yoshimura
    • Tetsuro Sasada
    • Takeshi Aoki
    • Masahiko Murakami
    • Tomoko Norose
    • Nobuyuki Ohike
    • Masafumi Takimoto
    • Shinichi Kobayashi
    • Takuya Tsunoda
    • Satoshi Wada
  • View Affiliations / Copyright

    Affiliations: Department of Clinical Diagnostic Oncology, Clinical Research Institute for Clinical Pharmacology and Therapeutics, Showa University, Tokyo 157‑8577, Japan, Kanagawa Cancer Center Research Institute, Yokohama, Kanagawa 241‑0815, Japan, Department of Molecular Preventive Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo 113‑0033, Japan, Department of Medicine, Division of Medical Oncology, School of Medicine, Showa University, Tokyo 157‑8577, Japan, Department of Surgery, Division of General and Gastroenterological Surgery, School of Medicine, Showa University, Tokyo 157‑8577, Japan, Department of Pathology and Laboratory Medicine, School of Medicine, Showa University, Tokyo 157‑8577, Japan, Clinical Research Institute for Clinical Pharmacology and Therapeutics, Showa University, Tokyo 157‑8577, Japan
    Copyright: © Ohkuma et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 57-69
    |
    Published online on: November 12, 2020
       https://doi.org/10.3892/ijo.2020.5147
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Abstract

Pancreatic cancer is associated with an exceedingly poor prognosis, warranting the development of novel therapeutic strategies and discovery of prognostic predictors. Given that chemoresistance‑related molecules are reportedly associated with the poor prognosis of pancreatic cancer, the present study aimed to identify molecules that could be efficacious therapeutic targets for pancreatic cancer. First, 10 patient‑derived xenografts (PDXs) were established from patients with pancreatic cancer. Subsequently, after treating tumor tissue generated from the PDXs with standard drugs, next‑generation sequencing (NGS) was performed using these tissues. The results of NGS analysis and immunohistochemical analysis on 80 pancreatic cancer tissues revealed that human epididymis protein 4 (HE4) expression in the anticancer drug‑treated PDX group was higher than that in the untreated PDXs. In addition, chemoresistance ability was observed in tumor cell lines overexpressing HE4. Furthermore, Kaplan‑Meier analysis of tumor tissues from 80 patients with pancreatic cancer was performed and it was found that patients with a high HE4 expression level had a poor survival rate compared with those who had a low HE4 expression level. Multivariate analysis also indicated the high expression level of HE4 was an independent poor prognostic biomarker. Thus, it was concluded that high gene and protein expression levels of HE4 mediate chemoresistance and are independent prognostic factors for pancreatic cancer.
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Copy and paste a formatted citation
Spandidos Publications style
Ohkuma R, Yada E, Ishikawa S, Komura D, Kubota Y, Hamada K, Horiike A, Ishiguro T, Hirasawa Y, Ariizumi H, Ariizumi H, et al: High levels of human epididymis protein 4 mRNA and protein expression are associated with chemoresistance and a poor prognosis in pancreatic cancer. Int J Oncol 58: 57-69, 2021.
APA
Ohkuma, R., Yada, E., Ishikawa, S., Komura, D., Kubota, Y., Hamada, K. ... Wada, S. (2021). High levels of human epididymis protein 4 mRNA and protein expression are associated with chemoresistance and a poor prognosis in pancreatic cancer. International Journal of Oncology, 58, 57-69. https://doi.org/10.3892/ijo.2020.5147
MLA
Ohkuma, R., Yada, E., Ishikawa, S., Komura, D., Kubota, Y., Hamada, K., Horiike, A., Ishiguro, T., Hirasawa, Y., Ariizumi, H., Shida, M., Watanabe, M., Onoue, R., Ando, K., Tsurutani, J., Yoshimura, K., Sasada, T., Aoki, T., Murakami, M., Norose, T., Ohike, N., Takimoto, M., Kobayashi, S., Tsunoda, T., Wada, S."High levels of human epididymis protein 4 mRNA and protein expression are associated with chemoresistance and a poor prognosis in pancreatic cancer". International Journal of Oncology 58.1 (2021): 57-69.
Chicago
Ohkuma, R., Yada, E., Ishikawa, S., Komura, D., Kubota, Y., Hamada, K., Horiike, A., Ishiguro, T., Hirasawa, Y., Ariizumi, H., Shida, M., Watanabe, M., Onoue, R., Ando, K., Tsurutani, J., Yoshimura, K., Sasada, T., Aoki, T., Murakami, M., Norose, T., Ohike, N., Takimoto, M., Kobayashi, S., Tsunoda, T., Wada, S."High levels of human epididymis protein 4 mRNA and protein expression are associated with chemoresistance and a poor prognosis in pancreatic cancer". International Journal of Oncology 58, no. 1 (2021): 57-69. https://doi.org/10.3892/ijo.2020.5147
Copy and paste a formatted citation
x
Spandidos Publications style
Ohkuma R, Yada E, Ishikawa S, Komura D, Kubota Y, Hamada K, Horiike A, Ishiguro T, Hirasawa Y, Ariizumi H, Ariizumi H, et al: High levels of human epididymis protein 4 mRNA and protein expression are associated with chemoresistance and a poor prognosis in pancreatic cancer. Int J Oncol 58: 57-69, 2021.
APA
Ohkuma, R., Yada, E., Ishikawa, S., Komura, D., Kubota, Y., Hamada, K. ... Wada, S. (2021). High levels of human epididymis protein 4 mRNA and protein expression are associated with chemoresistance and a poor prognosis in pancreatic cancer. International Journal of Oncology, 58, 57-69. https://doi.org/10.3892/ijo.2020.5147
MLA
Ohkuma, R., Yada, E., Ishikawa, S., Komura, D., Kubota, Y., Hamada, K., Horiike, A., Ishiguro, T., Hirasawa, Y., Ariizumi, H., Shida, M., Watanabe, M., Onoue, R., Ando, K., Tsurutani, J., Yoshimura, K., Sasada, T., Aoki, T., Murakami, M., Norose, T., Ohike, N., Takimoto, M., Kobayashi, S., Tsunoda, T., Wada, S."High levels of human epididymis protein 4 mRNA and protein expression are associated with chemoresistance and a poor prognosis in pancreatic cancer". International Journal of Oncology 58.1 (2021): 57-69.
Chicago
Ohkuma, R., Yada, E., Ishikawa, S., Komura, D., Kubota, Y., Hamada, K., Horiike, A., Ishiguro, T., Hirasawa, Y., Ariizumi, H., Shida, M., Watanabe, M., Onoue, R., Ando, K., Tsurutani, J., Yoshimura, K., Sasada, T., Aoki, T., Murakami, M., Norose, T., Ohike, N., Takimoto, M., Kobayashi, S., Tsunoda, T., Wada, S."High levels of human epididymis protein 4 mRNA and protein expression are associated with chemoresistance and a poor prognosis in pancreatic cancer". International Journal of Oncology 58, no. 1 (2021): 57-69. https://doi.org/10.3892/ijo.2020.5147
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