Marimuthu Arivusudar, Chavan Sandip, Sathe Gajanan, Sahasrabuddhe Nandini A, Srikanth Srinivas M, Renuse Santosh, Ahmad Sartaj, Radhakrishnan Aneesha, Barbhuiya Mustafa A, Kumar Rekha V, Harsha H C, Sidransky David, Califano Joseph, Pandey Akhilesh, Chatterjee Aditi
Institute of Bioinformatics, International Technology Park, Bangalore 560066, India.
Biochim Biophys Acta. 2013 Nov;1834(11):2308-16. doi: 10.1016/j.bbapap.2013.04.029. Epub 2013 May 7.
Protein biomarker discovery for early detection of head and neck squamous cell carcinoma (HNSCC) is a crucial unmet need to improve patient outcomes. Mass spectrometry-based proteomics has emerged as a promising tool for identification of biomarkers in different cancer types. Proteins secreted from cancer cells can serve as potential biomarkers for early diagnosis. In the current study, we have used isobaric tag for relative and absolute quantitation (iTRAQ) labeling methodology coupled with high resolution mass spectrometry to identify and quantitate secreted proteins from a panel of head and neck carcinoma cell lines. In all, we identified 2,472 proteins, of which 225 proteins were secreted at higher or lower abundance in HNSCC-derived cell lines. Of these, 148 were present in higher abundance and 77 were present in lower abundance in the cancer-cell derived secretome. We detected a higher abundance of some previously known markers for HNSCC including insulin like growth factor binding protein 3, IGFBP3 (11-fold) and opioid growth factor receptor, OGFR (10-fold) demonstrating the validity of our approach. We also identified several novel secreted proteins in HNSCC including olfactomedin-4, OLFM4 (12-fold) and hepatocyte growth factor activator, HGFA (5-fold). IHC-based validation was conducted in HNSCC using tissue microarrays which revealed overexpression of IGFBP3 and OLFM4 in 70% and 75% of the tested cases, respectively. Our study illustrates quantitative proteomics of secretome as a robust approach for identification of potential HNSCC biomarkers. This article is part of a Special Issue entitled: An Updated Secretome.
发现用于早期检测头颈部鳞状细胞癌（HNSCC）的蛋白质生物标志物是改善患者预后的一项关键且尚未满足的需求。基于质谱的蛋白质组学已成为在不同癌症类型中识别生物标志物的一种有前景的工具。癌细胞分泌的蛋白质可作为早期诊断的潜在生物标志物。在本研究中，我们使用了等压标签相对和绝对定量（iTRAQ）标记方法结合高分辨率质谱来识别和定量一组头颈部癌细胞系分泌的蛋白质。我们总共鉴定出2472种蛋白质，其中225种蛋白质在HNSCC来源的细胞系中分泌丰度较高或较低。其中，148种在癌细胞来源的分泌组中丰度较高，77种丰度较低。我们检测到一些先前已知的HNSCC标志物丰度较高，包括胰岛素样生长因子结合蛋白3（IGFBP3，11倍）和阿片样生长因子受体（OGFR，10倍），证明了我们方法的有效性。我们还在HNSCC中鉴定出几种新型分泌蛋白，包括嗅觉介质4（OLFM4，12倍）和肝细胞生长因子激活剂（HGFA，5倍）。使用组织微阵列在HNSCC中进行了基于免疫组化的验证，结果显示IGFBP3和OLFM4在分别70%和75%的测试病例中过表达。我们的研究表明，分泌组的定量蛋白质组学是识别潜在HNSCC生物标志物的一种可靠方法。本文是名为：更新后的分泌组的特刊的一部分。
