title: HADHA is a potential predictor of response to platinum-based chemotherapy for lung cancer.
abstract: To identify a cisplatin resistance predictor to reduce or prevent unnecessary side effects, we firstly established four cisplatin-resistant sub-lines and compared their protein profiles with cisplatin-sensitive parent lung cancer cell lines using two-dimensional gel electrophoresis. Between the cisplatin-resistant and -sensitive cells, a total of 359 protein spots were differently expressed (>1.5 fold), and 217 proteins (83.0%) were identified. We focused on a mitochondrial protein, hydroxyl-coenzyme A dehydrogenase/3-ketoacyl-coenzyme A thiolase/enoyl-coenzyme A hydratase alpha subunit (HADHA), which was increased in all cisplatin-resistant cells. Furthermore, pre- treated biopsy specimens taken from patients who showed resistance to platinum-based treatment showed a significantly higher positive rate for HADHA in all cases (p=0.00367), including non-small cell lung carcinomas (p=0.002), small-cell lung carcinomas (p=0.038), and adenocarcinomas (p=0.008). These results suggest that the expression of HADHA may be a useful marker to predict resistance to platinum-based chemotherapy in patients with lung cancer.
authors.affiliation: Department of Applied Tumor Pathology, GraKitasato University, Kanagawa, Japan.
authors.forename: Taihei
authors.initials: T
authors.lastname: Kageyama
authors.forename: Ryo
authors.initials: R
authors.lastname: Nagashio
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Ryuge
authors.forename: Toshihide
authors.initials: T
authors.lastname: Matsumoto
authors.forename: Akira
authors.initials: A
authors.lastname: Iyoda
authors.forename: Yukitoshi
authors.initials: Y
authors.lastname: Satoh
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Masuda
authors.forename: Shi-Xu
authors.initials: SX
authors.lastname: Jiang
authors.forename: Makoto
authors.initials: M
authors.lastname: Saegusa
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Sato
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D015153:Blotting, Western; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D016190:Carboplatin / Q000008:administration & dosage; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D002945:Cisplatin / Q000008:administration & dosage; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D015180:Electrophoresis, Gel, Two-Dimensional; D005047:Etoposide / Q000008:administration & dosage; D005500:Follow-Up Studies; D006801:Humans; D000077146:Irinotecan; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D063991:Mitochondrial Trifunctional Protein; D063992:Mitochondrial Trifunctional Protein, alpha Subunit; D009097:Multienzyme Complexes / Q000378:metabolism*; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000201:enzymology / Q000473:pathology; D017239:Paclitaxel / Q000008:administration & dosage; D011379:Prognosis; D055752:Small Cell Lung Carcinoma / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D014407:Tumor Cells, Cultured; D000093542:Gemcitabine
chemical_list: D009097:Multienzyme Complexes; D003841:Deoxycytidine; D005047:Etoposide; D000077146:Irinotecan; D016190:Carboplatin; C576205:HADHA protein, human; D063992:Mitochondrial Trifunctional Protein, alpha Subunit; D063991:Mitochondrial Trifunctional Protein; D017239:Paclitaxel; D002945:Cisplatin; D002166:Camptothecin; D000093542:Gemcitabine