通过多种不同蛋白质组学方法在胰腺癌的分泌蛋白质组中发现biomarker

        Quantitative proteomics can be used as a screening tool for identification of differentially expressed proteins as potential biomarkers for cancers. Candidate biomarkers from such studies can be subsequently tested using other techniques for use in early detection of cancers. Here, we demonstrate the use of Stable Isotope Labeling with Amino acids in Cell culture (SILAC) method to compare the secreted proteins (secretome) from pancreatic cancer-derived cells with that from non-neoplastic pancreatic ductal cells. We identified 145 differentially secreted proteins (>1.5 fold-change) several of which were previously reported as either upregulated (e.g. cathepsin D, M-CSF and fibronectin receptor) or downregulated (e.g. profilin 1 and IGFBP-7) proteins in pancreatic cancer, confirming the validity of our approach. In addition, we identified several proteins that have previously not been correlated with pancreatic cancer including perlecan (HSPG2), CD9 antigen, fibronectin receptor (integrin beta 1) and a novel cytokine designated as predicted osteoblast protein (FAM3C). The differential expression of a subset of these novel proteins was validated by Western blot analysis. In addition, overexpression of several proteins previously not described to be elevated in human pancreatic cancer (CD9, perlecan, SDF4, ApoE and fibronectin receptor) was confirmed by immunohistochemical labeling using pancreatic cancer tissue microarrays suggesting that these could be further pursued as potential biomarkers. Lastly, the protein expression data from SILAC were compared to mRNA expression data obtained using gene expression microarrays for the two cell lines (Panc1 and HPDE), and a correlation coefficient (r) of 0.28 was obtained, confirming previously reported poor associations between RNA and protein expression studies.

    定量蛋白质组学方法可以作为一个筛选方法来找到差异表达的蛋白质作为癌症的biomarker. 从这种方法筛选出来的候选者可以用其他的方法进一步的测试进而可以探测早期癌症。这篇文献中，作者阐述了细胞培养中稳定同位素标记氨基酸的方法来比较胰腺癌中的分泌蛋白质和正常胰腺中分泌蛋白质的差异，从而鉴定了145个差异表达的分泌蛋白质。后期又用多种方法来确认这些差异蛋白质的功能与作用作为癌症marker的蛋白质。

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