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Biomarker analysis to predict the pathological response to neoadjuvant chemotherapy in locally advanced gastric cancer: An exploratory biomarker study of COMPASS, a randomized phase II trial

Takashi Oshima, Takaki Yoshikawa _, Yohei Miyagi, Satoshi Morita, Michio Yamamoto, Kazuaki Tanabe, Kazuhiro Nishikawa, Yuichi Ito, Takanori Matsui, Yutaka Kimura, Tomoyuki Yokose, Yukihiko Hiroshima, Toru Aoyama, Tsutomu Hayashi, Takashi Ogata, Haruhiko Cho, Yasushi Rino, Munetaka Masuda, Akira Tsuburaya and Junichi Sakamoto

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Oncotarget. 2020; 11:2906-2918. https://doi.org/10.18632/oncotarget.27658

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Abstract

Takashi Oshima1, Takaki Yoshikawa2, Yohei Miyagi3, Satoshi Morita4, Michio Yamamoto5, Kazuaki Tanabe6, Kazuhiro Nishikawa7, Yuichi Ito8, Takanori Matsui9, Yutaka Kimura10, Tomoyuki Yokose13, Yukihiko Hiroshima3, Toru Aoyama11, Tsutomu Hayashi2, Takashi Ogata1, Haruhiko Cho12, Yasushi Rino11, Munetaka Masuda11, Akira Tsuburaya14 and Junichi Sakamoto15

1 Department of Gastrointestinal Surgery, Kanagawa Cancer Center, Asahi-ku, Yokohama, Kanagawa 241-8515, Japan

2 Department of Gastric Surgery, National Cancer Hospital, Chuo-ku, Tokyo 104-0045, Japan

3 Kanagawa Cancer Center Research Institute, Asahi-ku, Yokohama, Kanagawa 241-8515, Japan

4 Department of Biomedical Statistics and Bioinformatics, Kyoto University Graduate School of Medicine, Sakyo-ku, Kyoto, Kyoto 606-8507, Japan

5 Graduate School of Environmental and Life Science, Okayama University, Kita-ku, Okayama, Okayama 700-8530, Japan

6 Department of Gastroenterological and Transplant Surgery, Hiroshima University, Minami-ku, Hiroshima, Hiroshima 734-8551, Japan

7 Department of Surgery, National Hospital Organization Osaka National Hospital, Chuo-ku, Osaka, Osaka, 540-0006, Japan

8 Department of Gastroenterological Surgery, Aichi Cancer Center Hospital, Chikusa-ku, Nagoya, Aichi 464-8681, Japan

9 Department of Surgery, Aichi Cancer Center, Aichi Hospital, Kakemachi, Okazaki, Aichi 444-0011, Japan

10 Department of Surgery, NTT West Japan Osaka Hospital, Tennouji-ku, Osaka, Osaka 543-0042, Japan

11 Department of Surgery, Yokohama City University, Kanazawa-ku, Yokohama, Kanagawa 236-0004, Japan

12 Department of Gastric Surgery, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Bunkyo-ku, Tokyo 113-8677, Japan

13 Department of Pathology, Kanagawa Cancer Center, Asahi-ku, Yokohama, Kanagawa 241-8515, Japan

14 Department of Surgery, Ozawa Hospital, Odawara, Kanagawa 250-0012, Japan

15 Tokai Central Hospital, Kakamigahara, Gifu 504-8601, Japan

Correspondence to:

Takaki Yoshikawa,email: tayoshik@ncc.go.jp

Keywords: gastric cancer; neoadjuvant chemotherapy; pathological response; predictive biomarkers; personalized therapy

Received: November 24, 2018     Accepted: June 05, 2020     Published: July 28, 2020

ABSTRACT

Background: The findings of COMPASS, a randomized phase II study, suggested that the regimens and courses of neoadjuvant chemotherapy (NAC) for locally advanced gastric cancer (GC) did not affect the pathological response. However, pathological complete response was achieved in 10% patients who received four courses of either S-1/cisplatin or paclitaxel/cisplatin. We hypothesized that if relevant biomarkers could be used to predict the suitable NAC regimen before treatment initiation, further improvements could be ensured in the outcomes of locally advanced GC.

Materials and Methods: mRNA extraction, real-time polymerase chain reaction, and immunohistochemical analyses were performed using endoscopic biopsy specimens of primary tumors, collected prior to NAC, to determine the clinically relevant biomarkers.

Results: TIMP1, DSG2, RRM1, MUC2, EGFR, ZDHHC14, and CLDN18.2 were identified as biomarker candidates, since their expression was significantly associated with the pathological responses to each NAC regimen. Furthermore, TIMP1 and DSG2 were identified as predictive biomarkers of the pathological response to each NAC regimen.

Conclusions: The effective prediction of the pathological response to NAC regimens in locally advanced GC using biomarkers identified from endoscopic biopsy specimens indicates the possibility of personalizing NAC based on biomarker analysis.


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