AGR2 as a potential biomarker of human lung adenocarcinoma.

Osaka city medical journal Pub Date : 2012-06-01
Kyukwang Chung, Noritoshi Nishiyama, Hideki Wanibuchi, Shotaro Yamano, Shoji Hanada, Min Wei, Shigefumi Suehiro, Anna Kakehashi
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Abstract

Background: The present study aimed to identify useful candidate biomarkers of lung adenocarcinoma for clinical diagnosis and treatment using proteomics technology.

Methods: We assessed frequently highly overexpressed proteins in 12 cases of lung adenocarcinoma compared with adjacent normal tissue samples by liquid chromatography tandem mass spectrometry (LC-MS/MS) coupled with isobaric tags for relative and absolute quantitation (iTRAQ) technology, and validated the expression of target proteins by immunohistochemistry in 268 lung adenocarcinoma cases. Protein expression and clinicopathological variables were compared statistically for the evaluation of novel biomarkers.

Results: One hundred seventy-seven proteins displaying significant quantitative changes compared with adjacent normal-appearing lung tissue were identified in more than 9 out of 12 lung adenocarcinoma patients. Based on the results of liquid chromatography tandem mass spectrometry, Ingenuity Pathway, and immunohistochemical analyses, anterior gradient homolog 2 (AGR2) (upregulated 9.9-fold) was selected as a potential biomarker of human lung adenocarcinoma. AGR2 was positive in 94% of lung adenocarcinoma patients. Negative AGR2 expression was associated with poor survival (p = 0.007).

Conclusions: AGR2 is likely to become a biomarker for clinical applications.

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AGR2作为人肺腺癌的潜在生物标志物。
背景:本研究旨在利用蛋白质组学技术鉴定有用的肺腺癌候选生物标志物,用于临床诊断和治疗。方法:采用液相色谱-串联质谱(LC-MS/MS)联用相对绝对定量等压标记(iTRAQ)技术,对12例肺腺癌患者与邻近正常组织样本中频繁高表达的蛋白进行比较,并通过免疫组化方法验证268例肺腺癌患者靶蛋白的表达。对蛋白表达和临床病理变量进行统计学比较,评价新的生物标志物。结果:在12例肺腺癌患者中,有9例发现177种蛋白与邻近正常肺组织相比有显著的定量变化。基于液相色谱串联质谱、独创性途径和免疫组织化学分析的结果,选择前梯度同源物2 (AGR2)(上调9.9倍)作为人肺腺癌的潜在生物标志物。94%的肺腺癌患者AGR2阳性。AGR2阴性表达与生存率差相关(p = 0.007)。结论:AGR2有可能成为临床应用的生物标志物。
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