HADHA is a potential predictor of response to platinum-based chemotherapy for lung cancer.
HADHA is a potential predictor of response to platinum-based chemotherapy for lung cancer.
复制标题
DOI：
--
复制
发表时间：
2011
期刊：
影响因子：
--
通讯作者：
Taihei Kageyama;R. Nagashio;S. Ryuge;Toshihide Matsumoto;A. Iyoda;Y. Satoh;N. Masuda;Shi‐Xu Jiang;M. Saegusa;Yuichi Sato
中科院分区：
文献类型：
--
作者：
Taihei Kageyama;R. Nagashio;S. Ryuge;Toshihide Matsumoto;A. Iyoda;Y. Satoh;N. Masuda;Shi‐Xu Jiang;M. Saegusa;Yuichi Sato
为了确定顺铂耐药预测因子以减少或防止不必要的副作用，我们首先建立了四个顺铂耐药亚系，并使用二维凝胶电泳将其蛋白质谱与顺铂敏感亲本肺癌细胞系进行比较。在顺铂耐药细胞和顺铂敏感细胞之间，共有359个蛋白点存在差异表达（>1.5倍），鉴定出217个蛋白（83.0%）。我们重点关注线粒体蛋白，羟基辅酶 A 脱氢酶/3-酮脂酰辅酶 A 硫解酶/烯酰辅酶 A 水合酶 α 亚基 (HADHA)，该蛋白在所有顺铂耐药细胞中均有所增加。此外，取自对铂类治疗耐药的患者的预处理活检标本显示，所有病例中 HADHA 阳性率均显着较高 (p=0.00367)，包括非小细胞肺癌 (p=0.002)、小细胞肺癌 (p=0.038) 和腺癌 (p=0.008)。这些结果表明，HADHA 的表达可能是预测肺癌患者对铂类化疗耐药的有用标志物。
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.