Identification and Characterization of Potential Biomarkers by Quantitative Tissue Proteomics of Primary Lung Adenocarcinoma
Identification and Characterization of Potential Biomarkers by Quantitative Tissue Proteomics of Primary Lung Adenocarcinoma
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DOI：
10.1074/mcp.m115.057026
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发表时间：
2016-07-01
影响因子：
7
通讯作者：
Yu, Chia-Jung
中科院分区：
文献类型：
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作者：
Hsu, Chiung-Hung;Hsu, Chia-Wei;Yu, Chia-Jung
肺癌是全球癌症相关死亡的主要原因。诊断和预后生物标志物都是提高患者存活率的迫切需要。在这项研究中，我们使用基于iTRAQ的定量蛋白质组学分析，从不同程度的淋巴转移(LN)的配对腺癌(ADC)组织中鉴定/定量了1763个蛋白质。基于生物信息学分析和文献检索，我们从133个蛋白中筛选出6个候选蛋白(ERO1L、PABPC4、RCC1、RPS25、NARS和TARS)，这些蛋白在无LN转移的ADC肿瘤中的表达是邻近正常组织的1.5倍。免疫组织化学染色和Western印迹分析进一步证实了这6种蛋白的存在。与癌旁正常组织相比，这六种候选基因在肿瘤组织中的蛋白水平较高。ERO1L和NARS水平与LN转移呈正相关。重要的是，ERO1L在早期ADC患者中的过度表达与预后不良呈正相关，提示ERO1L在早期癌组织原发灶中的过度表达预示着肿瘤微转移的高风险。此外，我们发现ERO1L或NARS的敲除降低了ADC细胞的活力和迁移能力。我们的结果为ADC的诊断/预后提供了一个潜在的生物标志物数据集，并揭示了ERO1L和NARS在ADC进展中的新作用。
Lung cancer is the leading cause of cancer-related death worldwide. Both diagnostic and prognostic biomarkers are urgently needed to increase patient survival. In this study, we identified/quantified 1763 proteins from paired adenocarcinoma (ADC) tissues with different extents of lymph node (LN) involvement using an iTRAQ-based quantitative proteomic analysis. Based on a bioinformatics analysis and literature search, we selected six candidates (ERO1L, PABPC4, RCC1, RPS25, NARS, and TARS) from a set of 133 proteins that presented a 1.5-fold increase in expression in ADC tumors without LN metastasis compared with adjacent normal tissues. These six proteins were further verified using immunohistochemical staining and Western blot analyses. The protein levels of these six candidates were higher in tumor tissues compared with adjacent normal tissues. The ERO1L and NARS levels were positively associated with LN metastasis. Importantly, ERO1L overexpression in patients with early-stage ADC was positively correlated with poor survival, suggesting that ERO1L overexpression in primary sites of early-stage cancer tissues indicates a high risk for cancer micrometastasis. Moreover, we found that knockdown of either ERO1L or NARS reduced the viability and migration ability of ADC cells. Our results collectively provide a potential biomarker data set for ADC diagnosis/prognosis and reveal novel roles of ERO1L and NARS in ADC progression.