Oncotarget

Research Papers:

Serum level of hepatocyte growth factor is a novel marker of predicting the outcome and resistance to the treatment with trastuzumab in HER2-positive patients with metastatic gastric cancer

Naoki Takahashi, Koh Furuta, Hirokazu Taniguchi, Yusuke Sasaki, Hirokazu Shoji, Yoshitaka Honma, Satoru Iwasa, Natsuko Okita, Atsuo Takashima, Ken Kato, Tetsuya Hamaguchi, Yasuhiro Shimada and Yasuhide Yamada _

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Oncotarget. 2016; 7:4925-4938. https://doi.org/10.18632/oncotarget.6753

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Abstract

Naoki Takahashi1, Koh Furuta2, Hirokazu Taniguchi3, Yusuke Sasaki1, Hirokazu Shoji1, Yoshitaka Honma1, Satoru Iwasa1, Natsuko Okita1, Atsuo Takashima1, Ken Kato1, Tetsuya Hamaguchi1, Yasuhiro Shimada1,4, Yasuhide Yamada1

1Division of Gastrointestinal Oncology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan

2Division of Clinical Laboratories, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan

3Division of Pathology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan

4Division of Clinical Oncology, Kochi Health Sciences Center, 2125-1 Ike, Koch-city, Koch, 781–8555, Japan

Correspondence to:

Yasuhide Yamada, e-mail: yasuhide-yamada@amed.go.jp

Keywords: HER2, gastric cancer, trastuzumab, ligands, HGF

Received: July 04, 2015     Accepted: November 26, 2015     Published: December 24, 2015

ABSTRACT

HER2-overexpression in tumor tissue is observed in 6 to 23% of advanced gastric cancer (GC) cases, and trastuzumab is an active molecular drug for these patients. There are no data available on whether serum levels of ligands are associated with the response and resistance to trastuzumab in HER2-positive patients with metastatic GC. HER2 screening of 502 patients with advanced gastric cancer was performed in our institution. Among these patients, 84 patients (16.8%) were diagnosed as HER2-positive, and those who were treated with trastuzumab and met the inclusion criteria were enrolled in the present study. Serum levels of ligands that affect the HER2 signal pathway were measured by an enzyme-linked immunosorbent assay. Forty-six HER2-positive patients were enrolled in this study, and 26 patients (56.5%) achieved a partial response to treatment with trastuzumab. Among several ligands, the serum level of hepatocyte growth factor (HGF) was significantly lower in responders compared with that in non-responders (p = 0.014). Multivariate analyses showed that a high level of serum HGF was a poor prognostic factor for overall survival (OS) compared with low levels of HGF (adjusted HR: 3.857, 95% CI: 1.309–11.361, p = 0.014). Among 25 patients without initial disease progression on the treatment with trastuzumab, the mean value of serum HGF at disease progression was significantly higher than that at pre-treatment (p = 0.041). As novel findings, our study indicated that serum level of HGF was associated with tumor shrinkage and time to progression of trastuzumab in HER2-positive patients with metastatic GC.


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