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, Junichi Sakamoto

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

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.

Original languageEnglish
Pages (from-to)2906-2918
Number of pages13
JournalOncotarget
Volume11
Issue number30
DOIs
Publication statusPublished - Jul 28 2020

Keywords

  • Gastric cancer
  • Neoadjuvant chemotherapy
  • Pathological response
  • Personalized therapy
  • Predictive biomarkers

ASJC Scopus subject areas

  • Oncology

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