Qendro Veneta, Lundgren Deborah H, Rezaul Karim, Mahony Forrest, Ferrell Nicholas, Bi Andrew, Latifi Ardian, Chowdhury Daniyal, Gygi Steven, Haas Wilhelm, Wilson Lori, Murphy Michael, Han David K
Department of Cell Biology, Center for Vascular Biology, University of Connecticut Health Center , 263 Farmington Avenue, Farmington, Connecticut 06030, United States.
J Proteome Res. 2014 Nov 7;13(11):5031-40. doi: 10.1021/pr5006789. Epub 2014 Oct 16.
Melanoma is an aggressive type of skin cancer, which accounts for only 4% of skin cancer cases but causes around 75% of skin cancer deaths. Currently, there is a limited set of protein biomarkers that can distinguish melanoma subtypes and provide an accurate prognosis of melanoma. Thus, we have selected and profiled the proteomes of five different melanoma cell lines from different stages of progression in comparison with a normal melanocytes using tandem mass spectrometry. We also profiled the proteome of a solid metastatic melanoma tumor. This resulted in the identification of 4758 unique proteins, among which ∼200-300 differentially expressed proteins from each set were found by quantitative proteomics. Correlating protein expression with aggressiveness of each melanoma cell line and literature mining resulted in the final selection of six proteins: vimentin, nestin, fibronectin, annexin A1, dipeptidyl peptidase IV, and histone H2A1B. Validation of nestin and vimentin using 40 melanoma samples revealed pattern of protein expression can help predict melanoma aggressiveness in different subgroups of melanoma. These results, together with the combined list of 4758 expressed proteins, provide a valuable resource for selecting melanoma biomarkers in the future for the clinical and research community.
黑色素瘤是一种侵袭性皮肤癌,仅占皮肤癌病例的4%,但却导致约75%的皮肤癌死亡。目前,能够区分黑色素瘤亚型并准确预测黑色素瘤预后的蛋白质生物标志物数量有限。因此,我们使用串联质谱法,选择并分析了来自不同进展阶段的五种不同黑色素瘤细胞系的蛋白质组,并与正常黑素细胞进行了比较。我们还分析了一个实体转移性黑色素瘤肿瘤的蛋白质组。这导致鉴定出4758种独特蛋白质,其中通过定量蛋白质组学在每组中发现了约200 - 300种差异表达蛋白质。将蛋白质表达与每个黑色素瘤细胞系的侵袭性相关联,并通过文献挖掘,最终筛选出六种蛋白质:波形蛋白、巢蛋白、纤连蛋白、膜联蛋白A1、二肽基肽酶IV和组蛋白H2A1B。使用40个黑色素瘤样本对巢蛋白和波形蛋白进行验证,结果表明蛋白质表达模式有助于预测黑色素瘤不同亚组中的侵袭性。这些结果,连同4758种表达蛋白质的综合列表,为未来临床和研究界选择黑色素瘤生物标志物提供了宝贵资源。