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

生物标志物分析预测局部晚期胃癌新辅助化疗的病理反应:一项随机 II 期临床试验 COMPASS 的探索性生物标志物研究

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作者: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 Tsubur

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

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.

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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