Overexpression of optic atrophy 1 protein increases cisplatin resistance via inactivation of caspase-dependent apoptosis in lung adenocarcinoma cells

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. (C) 2012 Elsevier Inc. All rights reserved.