Identification and verification of transgelin-2 as a potential biomarker of tumor-derived lung-cancer endothelial cells by comparative proteomics
Identification and verification of transgelin-2 as a potential biomarker of tumor-derived lung-cancer endothelial cells by comparative proteomics
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通过比较蛋白质组学鉴定和验证transgelin-2作为肿瘤源性肺癌内皮细胞的潜在生物标志物
DOI：
10.1016/j.jprot.2015.12.012
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发表时间：
2016-05-16
影响因子：
3.3
通讯作者：
Zhuo, Huiqin
中科院分区：
文献类型：
--
作者：
Jin, Hongwei;Cheng, Xiao;Zhuo, Huiqin
为了研究肿瘤微环境中内皮细胞（EC）的异质性和抗肿瘤血管生成治疗的生物标志物，通过免疫磁性分离从荷0.5 cm肿瘤的小鼠刘易斯肺癌模型中纯化高纯度（>98%）正常（NEC）和肿瘤衍生的CD 105（+）EC（TEC）。蛋白质组学分析显示，48个蛋白质（28上调和20下调）差异调节至少1.5倍的TEC，这些蛋白质参与代谢，能量途径，蛋白质折叠，细胞生长和/或作为细胞骨架的结构成分。热休克蛋白60（Hspdl）和transgelin-2（Tagln 2）的上调，揭示了在TEC，并通过免疫组织化学（IHC）在配对组织从30个连续的肺癌（LC）患者。Hspdl、Tagln 2在癌旁和癌组织微血管内皮细胞中的表达水平均高于正常对照组。较强的Tagln 2染色与临床分期、肿瘤大小和组织学神经浸润相关。在LC患者血清中检测到较高的Hspdl（曲线下面积[AUC]，0.82）和较低的Tagln 2（AUC，0.90）水平。Pearson相关分析显示血清Hspdl和Tagln 2水平之间呈正相关。总之，较高的Tagln 2水平与肿瘤的发展，淋巴结转移，和神经侵袭在LC，因此可能作为一个潜在的生物标志物的肿瘤angiogenesis.Significance：高纯度的内皮细胞（正常和肿瘤衍生）的特点ECs异质性在肿瘤微环境和探索肿瘤发展的早期阶段的生物标志物的蛋白质组学。候选蛋白Hspdl和Tagln 2在肺癌患者血清和肿瘤组织中得到进一步验证。此外，较高的Tagln 2与临床肿瘤发展、转移和神经侵袭显著相关。所有这些结果表明Tagln 2在TEC中对肿瘤的发展和转移起着至关重要的作用。(C)2015 Elsevier B. V.版权所有。
To investigate heterogeneity of endothelial cells (ECs) in the tumor microenvironment and biomarkers for antitumor angiogenesis therapy, high-purity (>98%) normal (NECs) and tumor-derived CD105(+) ECs (TECs) were purified from a mouse Lewis lung carcinoma model bearing 0.5 cm tumors by immunomagnetic separation. Proteomics analysis revealed that 48 proteins (28 upregulated and 20 downregulated) were differentially regulated by at least 1.5-fold in TECs, and that these proteins were involved in metabolism, energy pathways, protein folding, cell growth and/or functioned as structural constituents of the cytoskeleton. Upregulation of heat shock protein 60 (Hspdl) and transgelin-2 (Tagln2) was revealed in TECs, and by immunohistochemistry (IHC) in paired tissues from 30 consecutive lung cancer (LC) patients. Higher expression levels of Hspdl, Tagln2 were detected in microvascular ECs of paratumor and tumor tissues than in paired normal counterparts. Stronger Tagln2 staining was associated with clinical stage, tumor size, and histological neural invasion. Higher Hspdl (area under the curve [AUC], 0.82) and lower Tagln2 (AUC, 0.90) levels were detected in LC patient sera. Pearson correlation analysis revealed a positive correlation between serum Hspdl and Tagln2 levels. In conclusion, higher Tagln2 levels were associated with tumor development, lymph node metastasis, and neural invasion in LC and may thus serve as a potential biomarker of tumor angiogenesis.Significance: High-purity endothelial cells (normal and tumor derived) were prepared to characterize ECs heterogeneity in the tumor microenvironment and to explore biomarkers of early stages of tumor development by proteomics. Candidate proteins Hspdl and Tagln2, were further verification in the sera and tumor tissues of lung cancer patients. Moreover, higher Tagln2 was significantly associated with clinical tumor development, metastasis, and neural invasion. All these results indicated a crucial role for Tagln2 in TECs for tumor development and metastasis. (C) 2015 Elsevier B.V. All rights reserved.