Quantitative tissue proteomics of esophageal squamous cell carcinoma for novel biomarker discovery
Quantitative tissue proteomics of esophageal squamous cell carcinoma for novel biomarker discovery
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DOI：
10.4161/cbt.12.6.16833
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发表时间：
2011-09-15
影响因子：
3.6
通讯作者：
Pandey, Akhilesh
中科院分区：
文献类型：
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作者：
Pawar, Harsh;Kashyap, Manoj Kumar;Pandey, Akhilesh
食道鳞状细胞癌(ESCC)是世界十大常见恶性肿瘤之一。在这项研究中，我们的目标是通过使用相对和绝对定量等压标签(ITRAQ)的定量蛋白质组学方法来识别ESCC的潜在生物标记物。我们比较了来自10名患者的ESCC肿瘤组织和相应的邻近正常组织的蛋白质表达谱。在高精度的QTOF质谱仪上对强阳离子交换层析组分进行了LC-MS/MS分析，鉴定了687种蛋白质。总共有257个蛋白质被鉴定为在ESCC中与正常组织相比差异表达。我们发现了几个已知的蛋白质生物标志物在ESCC中上调，包括血栓反应蛋白1(THBS1)、周膜蛋白1(POSTN)和热休克70 kDa蛋白9(HSPA9)，证实了我们方法的有效性。此外，在我们的筛选中还鉴定了几个以前没有报道的新蛋白。这些新的候选生物标志物包括丙皂苷(PSAP)、凝集素1(PLEC1)和蛋白二硫键异构酶A4(PDIA4)，通过组织芯片的免疫组织化学标记进一步证实它们是过表达的。我们研究的成功表明，这种质谱学策略可以应用于一般癌症，以开发一组候选生物标记物，然后可以通过其他技术进行验证。
Esophageal squamous cell carcinoma (ESCC) is among the top ten most frequent malignancies worldwide. In this study, our objective was to identify potential biomarkers for ESCC through a quantitative proteomic approach using the isobaric tags for relative and absolute quantitation (iTRAQ) approach. We compared the protein expression profiles of ESCC tumor tissues with the corresponding adjacent normal tissue from ten patients. LC-MS/MS analysis of strong cation exchange chromatography fractions was performed on an Accurate Mass QTOF mass spectrometer, which led to the identification of 687 proteins. In all, 257 proteins were identified as differentially expressed in ESCC as compared with normal. We found several previously known protein biomarkers to be upregulated in ESCC including thrombospondin 1 (THBS1), periostin 1 (POSTN) and heat shock 70 kDa protein 9 (HSPA9) confirming the validity of our approach. In addition, several novel proteins that had not been reported previously were identified in our screen. These novel biomarker candidates included prosaposin (PSAP), plectin 1 (PLEC1) and protein disulfide isomerase A 4 (PDIA4) that were further validated to be overexpressed by immunohistochemical labeling using tissue microarrays. The success of our study shows that this mass spectrometric strategy can be applied to cancers in general to develop a panel of candidate biomarkers, which can then be validated by other techniques.