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人小细胞肺癌组织的蛋白质组学分析:协同蛋白样蛋白-1 的上调。

Proteomic analysis of human small cell lung cancer tissues: up-regulation of coactosin-like protein-1.

机构信息

Division of Respiratory and Critical Medicine, Department of Internal Medicine, College of Life Science, CHA University, Sungnam, Republic of Korea.

出版信息

J Proteome Res. 2011 Jan 7;10(1):269-76. doi: 10.1021/pr100714b. Epub 2010 Dec 2.

DOI:10.1021/pr100714b
PMID:21047053
Abstract

Small cell lung cancer (SCLC) is the leading cause of cancer death, with a high propensity for aggressiveness and metastasis even in an early stage. Thus, identification of biomarkers as early diagnostics and treatment is needed. In this study, we investigated differentially regulated proteins between human SCLC tissues and normal bronchial epithelium by proteomic analysis using two-dimensional electrophoresis (2-DE) and MALDI-TOF mass spectrometry. Seven proteins and protein isoforms, including, γ-actin, tubulin α-1B, laminin B1, coactosin-like protein-1 (COTL-1), ubiquitin carboxyl-terminal esterase L1, ubiquitin-conjugating enzyme E2-25K, and carbonic anhydrase 1, were up-regulated more than 2 fold in SCLC tissues. In particular, up-regulated COTL-1 expression was validated by Western blot analysis, immunohistochemistry, and reverse transcription quantitative polymerase chain reaction (RT-qPCR). Moreover, most SCLC tissues (93%; 28/30) were COTL-1-positive in immunohistochemistry, whereas only 16% (10/64) of nonsmall cell lung cancer (NSLC) tissues were. Taken together, this SCLC proteomic data may help in establishing a human SCLC proteome database. COTL-1 may be a biomarker or a therapeutic target in SCLC patients.

摘要

小细胞肺癌(SCLC)是癌症死亡的主要原因,即使在早期阶段,其侵袭性和转移性也很强。因此,需要鉴定生物标志物作为早期诊断和治疗。在这项研究中,我们通过二维电泳(2-DE)和 MALDI-TOF 质谱分析,研究了人 SCLC 组织和正常支气管上皮组织之间差异调节的蛋白质。七种蛋白质和蛋白异构体,包括 γ-肌动蛋白、微管蛋白 α-1B、层粘连蛋白 B1、协同蛋白样蛋白-1(COTL-1)、泛素羧基末端酯酶 L1、泛素结合酶 E2-25K 和碳酸酐酶 1,在 SCLC 组织中上调超过 2 倍。特别是,通过 Western blot 分析、免疫组织化学和反转录定量聚合酶链反应(RT-qPCR)验证了上调的 COTL-1 表达。此外,在免疫组织化学中,93%(28/30)的 SCLC 组织呈 COTL-1 阳性,而在非小细胞肺癌(NSCLC)组织中仅为 16%(10/64)。总之,这项 SCLC 蛋白质组学数据可能有助于建立人类 SCLC 蛋白质组数据库。COTL-1 可能是 SCLC 患者的生物标志物或治疗靶点。

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