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Reaction of plasma hepatocyte growth factor levels in non‐small cell lung cancer patients treated with EGFR‐TKIs
Author(s) -
Tanaka Hidenori,
Kimura Tatsuo,
Kudoh Shinzoh,
Mitsuoka Shigeki,
Watanabe Tetsuya,
Suzumura Tomohiro,
Tachibana Keisei,
Noguchi Masayuki,
Yano Seiji,
Hirata Kazuto
Publication year - 2011
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.25799
Subject(s) - lung cancer , hepatocyte growth factor , hepatocyte , medicine , lung , cancer research , growth factor , oncology , biology , receptor , biochemistry , in vitro
Hepatocyte growth factor induces resistance to epidermal growth factor receptor tyrosine kinase inhibitors. It has been hypothesized that epidermal growth factor receptor tyrosine kinase inhibitors administration may influence the levels of plasma hepatocyte growth factor. Patients with advanced non‐small cell lung cancer and relapsed after chemotherapies were eligible. Plasma hepatocyte growth factor levels were analyzed on pretreatment and post‐treatment day 15 and 30. We also investigated the correlation between plasma hepatocyte growth factor levels and sensitivity to epidermal growth factor receptor tyrosine kinase inhibitors, tissue immunoreactivity for hepatocyte growth factor and MET gene status. Thirty‐one patients were enrolled. Plasma hepatocyte growth factor levels on post‐treatment day 15 (630.1 ± 366.9 pg/ml) were significantly higher ( p = 0.029) than the pretreatment plasma hepatocyte growth factor levels (485.9 ± 230.2 pg/ml). Plasma hepatocyte growth factor levels on the post‐treatment day 30 (581.5 ± 298.1 pg/ml) tend to be higher than those before treatment ( p = 0.057). Pretreatment plasma hepatocyte growth factor levels in patients with progressive disease (724.1 ± 216.4 pg/ml) were significantly higher than those in patients with stable disease (396.5 ± 148.3 pg/ml; p = 0.0008) and partial response (381.7 ± 179.0 pg/ml; p = 0.0039). The optimal pretreatment plasma hepatocyte growth factor cut‐off value for diagnosis of responder was 553.5 pg/ml, and its sensitivity and specificity were 90% and 65%, respectively. Pretreatment plasma hepatocyte growth factor levels had no correlation with tissue immunoreactivities for hepatocyte growth factor, MET gene status and active EGFR mutations. Administration of epidermal growth factor receptor tyrosine kinase inhibitors significantly increased plasma hepatocyte growth factor levels. High levels of pretreatment plasma hepatocyte growth factor indicated intrinsic resistance to epidermal growth factor receptor tyrosine kinase inhibitors. Plasma hepatocyte growth factor can serve as a useful biomarker for the early diagnosis of tumor relapse treated with epidermal growth factor receptor tyrosine kinase inhibitors.