title: Overexpression of optic atrophy 1 protein increases cisplatin resistance via inactivation of caspase-dependent apoptosis in lung adenocarcinoma cells.
abstract: Optic atrophy 1 protein, a 112-kd guanosine triphosphatase, is involved in the mitochondrial inner membrane fusion and anticancer drug-mediated cytotoxicity, which implicate an association with disease progression of the cancer. In this study, we investigated the prognostic value of optic atrophy 1 expression in patients with lung adenocarcinoma. Using immunohistochemical staining, expression of optic atrophy 1 was determined in 286 lung adenocarcinoma patients. Expression of optic atrophy 1 was confirmed by immunoblotting. The relationship between optic atrophy 1 expression and clinicopathological parameters was analyzed statistically by comparing survival between different groups using the log-rank test. The results showed that optic atrophy 1 overexpression was detected in 219 (76.6%) of lung adenocarcinoma patients. A significant difference was found in cumulative survival between patients with high optic atrophy 1 levels and those with low optic atrophy 1 levels (P = .0016). In the in vitro experiments with cell lines, silencing of optic atrophy 1 expression reduced cisplatin resistance, which was further shown via increased release of cytochrome c and activation of caspase-dependent apoptotic pathway. In conclusion, optic atrophy 1 is highly expressed in lung adenocarcinoma and indicates poor prognosis.
authors.affiliation: Department of Surgery, China Medical University Hospital, China Medical University, Taichung, Taiwan 40452.
authors.forename: Hsin-Yuan
authors.initials: HY
authors.lastname: Fang
authors.forename: Chih-Yi
authors.initials: CY
authors.lastname: Chen
authors.forename: Shiow-Her
authors.initials: SH
authors.lastname: Chiou
authors.forename: Yu-Ting
authors.initials: YT
authors.lastname: Wang
authors.forename: Tze-Yi
authors.initials: TY
authors.lastname: Lin
authors.forename: Hui-Wen
authors.initials: HW
authors.lastname: Chang
authors.forename: I-Ping
authors.initials: IP
authors.lastname: Chiang
authors.forename: Kuo-Jung
authors.initials: KJ
authors.lastname: Lan
authors.forename: Kuan-Chih
authors.initials: KC
authors.lastname: Chow
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis* / Q000188:drug therapy / Q000378:metabolism / Q000401:mortality; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism*; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects* / Q000235:genetics; D005260:Female; D020558:GTP Phosphohydrolases / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008175:Lung Neoplasms / Q000175:diagnosis* / Q000188:drug therapy / Q000378:metabolism / Q000401:mortality; D008297:Male; D009367:Neoplasm Staging; D012333:RNA, Messenger / Q000378:metabolism; D015996:Survival Rate; D013624:Taiwan / Q000453:epidemiology
chemical_list: D000970:Antineoplastic Agents; D061945:Caspase Inhibitors; D012333:RNA, Messenger; D020169:Caspases; D020558:GTP Phosphohydrolases; C415198:OPA1 protein, human; D002945:Cisplatin