title: 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.
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.
authors.affiliation: Division of Gastrointestinal Oncology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Takahashi
authors.affiliation: Division of Clinical Laboratories, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan.
authors.forename: Koh
authors.initials: K
authors.lastname: Furuta
authors.affiliation: Division of Pathology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan.
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Taniguchi
authors.affiliation: Division of Gastrointestinal Oncology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Sasaki
authors.affiliation: Division of Gastrointestinal Oncology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan.
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Shoji
authors.affiliation: Division of Gastrointestinal Oncology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan.
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Honma
authors.affiliation: Division of Gastrointestinal Oncology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan.
authors.forename: Satoru
authors.initials: S
authors.lastname: Iwasa
authors.affiliation: Division of Gastrointestinal Oncology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan.
authors.forename: Natsuko
authors.initials: N
authors.lastname: Okita
authors.affiliation: Division of Gastrointestinal Oncology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan.
authors.forename: Atsuo
authors.initials: A
authors.lastname: Takashima
authors.affiliation: Division of Gastrointestinal Oncology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan.
authors.forename: Ken
authors.initials: K
authors.lastname: Kato
authors.affiliation: Division of Gastrointestinal Oncology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Hamaguchi
authors.affiliation: Division of Gastrointestinal Oncology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan.|Division of Clinical Oncology, Kochi Health Sciences Center, 2125-1 Ike, Koch-city, Koch, 781-8555, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Shimada
authors.affiliation: Division of Gastrointestinal Oncology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan.
authors.forename: Yasuhide
authors.initials: Y
authors.lastname: Yamada
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000097:blood; D019008:Drug Resistance, Neoplasm; D005260:Female; D005500:Follow-Up Studies; D017228:Hepatocyte Growth Factor / Q000097:blood*; D006801:Humans; D007124:Immunoenzyme Techniques; D008113:Liver Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000556:secondary*; D008175:Lung Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000556:secondary*; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D010534:Peritoneal Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000556:secondary*; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D015996:Survival Rate; D000068878:Trastuzumab / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D017228:Hepatocyte Growth Factor; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C066855:HGF protein, human; C508053:ERBB2 protein, human
keywords: HER2; HGF; gastric cancer; ligands; trastuzumab