期刊
JOURNAL OF THORACIC ONCOLOGY
卷 8, 期 2, 页码 161-170出版社
ELSEVIER SCIENCE INC
DOI: 10.1097/JTO.0b013e31827d5237
关键词
Baculoviral inhibitors of apoptosis proteins repeat-containing 6; Prognostic factor; Non-small-cell lung cancer; Recurrence; Patient survival; Chemoresistance
资金
- Genome Canada
- Canadian Institutes of Health Research
Introduction: Non-small-cell lung cancer (NSCLC) is an aggressive, highly chemoresistant disease. Reliable prognostic assays and more effective treatments are critically required. BIRC6 (baculoviral inhibitors of apoptosis proteins repeat-containing 6) protein is a member of the inhibitors of apoptosis protein family thought to play an important role in the progression or chemoresistance of many cancers. In this study, we investigated whether BIRC6 expression can be used as a prognostic marker or potential therapeutic target for NSCLC. Methods: In a retrospective analysis, BIRC6 protein expression was determined for 78 resected primary NSCLCs and nine benign lung tissues. Twenty-nine chemoresistant or chemosensitive subrenal capsule NSCLC tissue xenografts were assessed for BIRC6 expression, using immunohistochemistry, and 13 of them for BIRC6 gene copy number, using array comparative genomic hybridization analysis. The effect of small interfering RNA-induced BIRC6 knockdown on the growth of human NSCLC cell cultures and apoptosis (in combination with cisplatin) was investigated. Results: Elevated BIRC6 protein expression in NSCLC tissues was associated with poor 3-year relapse-free patient survival, lymph node involvement, and advanced pathological tumor, node, metastasis stage. In patient-derived lung squamous cell carcinoma xenografts, chemoresistance was associated with elevated BIRC6 expression and increased gene copy number. Small interfering RNA-induced BIRC6 down-regulation inhibited growth of the NSCLC cells and sensitized the cells to cisplatin. Conclusions: BIRC6 may play an important role in the malignant progression and chemoresistance of NSCLC. Elevated BIRC6 protein expression may serve as a predictive marker for chemoresistance of NSCLCs and a poor prognostic factor for NSCLC patients. Downregulation of the BIRC6 gene as a therapeutic approach may be effective, especially in combination with conventional chemotherapeutics.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据