title: Usefulness of plasma HGF level for monitoring acquired resistance to EGFR tyrosine kinase inhibitors in non-small cell lung cancer.
abstract: Monitoring of molecular markers is indispensable for deciding subsequent treatment after acquired resistance to molecular-targeted therapy. According to results using re-biopsy, EGFR T790M mutation and overexpression of hepatocyte growth factor (HGF) are major mechanisms of acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). The aim of the present study was to assess whether quantification of HGF using peripheral blood in addition to detection of T790M with plasma DNA is useful for monitoring as an alternative to invasive re-biopsy. HGF levels in plasma were determined using ELISA and T790M mutation was detected using mutation-biased PCR and quenched probe system (MBP-QP). The median level of HGF in plasma at baseline was 140 pg/ml and was significantly higher in the advanced stage of cancer and in smokers and predicted poor survival as determined using 315 plasma samples from 225 lung cancer patients. T790M was detected with plasma DNA in 9 of 16 patients who acquired resistance to EGFR-TKIs and a greater than 1.5-fold elevation compared with pretreatment HGF levels was observed in 6 patients after acquired resistance. Eleven of 16 patients (69%) showed either HGF elevation or T790M in plasma samples, with both outcomes observed in 25% of patients; this is consistent with results based on re-biopsy reported from other laboratories. Considering these results, assessing HGF and T790M using peripheral blood could be useful for monitoring mechanisms of acquired resistance to EGFR-TKIs.
authors.affiliation: Division of Hematology, Respiratory Medicine and Oncology, Department of Internal Medicine, Faculty of Medicine, Saga University, Saga 849-8501, Japan.
authors.forename: Hitomi
authors.initials: H
authors.lastname: Umeguchi
authors.affiliation: Division of Hematology, Respiratory Medicine and Oncology, Department of Internal Medicine, Faculty of Medicine, Saga University, Saga 849-8501, Japan.
authors.forename: Naoko
authors.initials: N
authors.lastname: Sueoka-Aragane
authors.affiliation: Division of Hematology, Respiratory Medicine and Oncology, Department of Internal Medicine, Faculty of Medicine, Saga University, Saga 849-8501, Japan.
authors.forename: Naomi
authors.initials: N
authors.lastname: Kobayashi
authors.affiliation: Division of Hematology, Respiratory Medicine and Oncology, Department of Internal Medicine, Faculty of Medicine, Saga University, Saga 849-8501, Japan.
authors.forename: Tomomi
authors.initials: T
authors.lastname: Nakamura
authors.affiliation: Division of Hematology, Respiratory Medicine and Oncology, Department of Internal Medicine, Faculty of Medicine, Saga University, Saga 849-8501, Japan.
authors.forename: Akemi
authors.initials: A
authors.lastname: Sato
authors.affiliation: Department of Thoracic Surgery, Faculty of Medicine, Saga University, Saga 849-8501, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Takeda
authors.affiliation: Division of Hematology, Respiratory Medicine and Oncology, Department of Internal Medicine, Faculty of Medicine, Saga University, Saga 849-8501, Japan.
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Hayashi
authors.affiliation: Department of Laboratory Medicine, Saga University Hospital, Saga 849-8501, Japan.
authors.forename: Eisaburo
authors.initials: E
authors.lastname: Sueoka
authors.affiliation: Division of Hematology, Respiratory Medicine and Oncology, Department of Internal Medicine, Faculty of Medicine, Saga University, Saga 849-8501, Japan.
authors.forename: Shinya
authors.initials: S
authors.lastname: Kimura
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D002289:Carcinoma, Non-Small-Cell Lung / Q000097:blood / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D016903:Drug Monitoring; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D004797:Enzyme-Linked Immunosorbent Assay; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000235:genetics; D005260:Female; D017228:Hepatocyte Growth Factor / Q000097:blood*; D006801:Humans; D008175:Lung Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D016133:Polymerase Chain Reaction / Q000379:methods; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; C066855:HGF protein, human; D047428:Protein Kinase Inhibitors; D017228:Hepatocyte Growth Factor; C512478:EGFR protein, human; D066246:ErbB Receptors