SELBENP1 下调在人支气管上皮癌变过程中的功能和意义。
The function and significance of SELENBP1 downregulation in human bronchial epithelial carcinogenic process.
机构信息
Key Laboratory of Cancer Proteomics of Chinese Ministry of Health, Xiangya Hospital, Central South University, Changsha, Hunan, China ; School of Nursing, University of South China, Hengyang, Hunan, China.
出版信息
PLoS One. 2013 Aug 19;8(8):e71865. doi: 10.1371/journal.pone.0071865. eCollection 2013.
BACKGROUND
Our quantitative proteomic study showed that selenium-binding protein 1 (SELENBP1) was progressively decreased in human bronchial epithelial carcinogenic process. However, there is little information on expression and function of SELENBP1 during human lung squamous cell cancer (LSCC) carcinogenesis.
METHODS
iTRAQ-tagging combined with 2D LC-MS/MS analysis was used to identify differentially expressed proteins in the human bronchial epithelial carcinogenic process. SELENBP1, member of selenoproteins family and progressively downregulated in this process, was selected to further study. Both Western blotting and immunohistochemistry were performed to detect SELENBP1 expression in independent sets of tissues of bronchial epithelial carcinogenesis, and ability of SELENBP1 for discriminating NBE (normal bronchial epithelium) from preneoplastic lesions from invasive LSCC was evaluated. The effects of SELENBP1 downregulation on the susceptibility of benzo(a)pyrene (B[a]P)-induced human bronchial epithelial cell transformation were determined.
RESULTS
102 differentially expressed proteins were identified by quantitative proteomics, and SELENBP1 was found and confirmed being progressively decreased in the human bronchial epithelial carcinogenic process. The sensitivity and specificity of SELENBP1 were 80% and 79% in discriminating NBE from preneoplastic lesions, 79% and 82% in discriminating NBE from invasive LSCC, and 77% and 71% in discriminating preneoplastic lesions from invasive LSCC, respectively. Furthermore, knockdown of SELENBP1 in immortalized human bronchial epithelial cell line 16HBE cells significantly increased the efficiency of B[a]P-induced cell transformation.
CONCLUSIONS
The present data shows for the first time that decreased SELENBP1 is an early event in LSCC, increases B[a]P-induced human bronchial epithelial cell transformation, and might serve as a novel potential biomarker for early detection of LSCC.
背景
我们的定量蛋白质组学研究表明，硒结合蛋白 1（SELENBP1）在人类支气管上皮癌变过程中逐渐减少。然而，关于 SELENBP1 在人类肺鳞癌（LSCC）癌变过程中的表达和功能的信息很少。
方法
采用 iTRAQ 标记结合 2D LC-MS/MS 分析鉴定人类支气管上皮癌变过程中的差异表达蛋白。选择 SELENBP1，作为该过程中逐渐下调的硒蛋白家族成员，进一步研究。采用 Western blot 和免疫组织化学法检测支气管上皮癌变过程中独立组织样本中 SELENBP1 的表达，并评估 SELENBP1 区分正常支气管上皮（NBE）与癌前病变和侵袭性 LSCC 的能力。检测 SELENBP1 下调对苯并[a]芘（B[a]P）诱导的人支气管上皮细胞转化易感性的影响。
结果
通过定量蛋白质组学鉴定出 102 个差异表达蛋白，发现并证实 SELENBP1 在人类支气管上皮癌变过程中逐渐减少。SELENBP1 区分 NBE 与癌前病变的敏感性和特异性分别为 80%和 79%，区分 NBE 与侵袭性 LSCC 的敏感性和特异性分别为 79%和 82%，区分癌前病变与侵袭性 LSCC 的敏感性和特异性分别为 77%和 71%。此外，在永生化人支气管上皮细胞系 16HBE 细胞中敲低 SELENBP1 显著增加了 B[a]P 诱导的细胞转化效率。
结论
本研究首次表明，SELENBP1 的减少是 LSCC 的早期事件，增加了 B[a]P 诱导的人支气管上皮细胞转化，可能作为 LSCC 早期检测的一种新的潜在生物标志物。
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