Quantitative proteomic analysis of oral brush biopsies identifies secretory leukocyte protease inhibitor as a promising, mechanism-based oral cancer biomarker.
Quantitative proteomic analysis of oral brush biopsies identifies secretory leukocyte protease inhibitor as a promising, mechanism-based oral cancer biomarker.
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口腔刷活检的定量蛋白质组学分析确定分泌性白细胞蛋白酶抑制剂是一种有前景的基于机制的口腔癌生物标志物
DOI：
10.1371/journal.pone.0095389
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Griffin TJ
中科院分区：
文献类型：
--
作者：
Yang Y;Rhodus NL;Ondrey FG;Wuertz BR;Chen X;Zhu Y;Griffin TJ
降低口腔癌近50%的死亡率是迫切需要的。早期诊断的改进和更有效的预防性治疗可能会影响这种下降。为此，我们首次对非侵入性收集的口腔刷活检进行了深入的基于质谱的定量鸟枪蛋白质组学研究。比较了从健康正常组织、口腔癌前病变组织（OPML）、口腔鳞状细胞癌（OSCC）和匹配对照组织的刷检活检中分离的蛋白质。在复制的蛋白质组数据集中，分泌性白细胞蛋白酶抑制剂（SLPI）蛋白突出的基础上，其在OPML和口腔鳞状细胞癌病变组织相比，健康的正常组织中的丰度下降。在另外的刷检活检样本中的蛋白质印迹证实了在健康的正常组织和OPML组织之间SLPI丰度逐渐降低的趋势，其中在OSCC病变组织中降低更大。在体外比较模型OPML和OSCC细胞系观察到类似的SLPI降低。此外，患者全唾液中脱落的口腔细胞显示SLPI的丢失与口腔癌进展相关。这些结果结合蛋白质组学数据表明，与健康正常组织的组织相比，OSCC患者匹配的健康对照组织中的SLPI降低，表明口腔细胞中SLPI的全身性降低与口腔癌的发展相关。最后，体外实验表明，SLPI治疗显著降低了OPML细胞系中的NF-κ B活性。研究结果表明OPML的抗炎活性，支持SLPI在OSCC进展中的机制作用，并表明其对高危口腔病变的预防性治疗的潜力。总的来说，我们的研究结果首次显示SLPI作为口腔癌进展的基于机制的非侵入性生物标志物的潜力，具有预防性治疗的潜力。
A decrease in the almost fifty percent mortality rate from oral cancer is needed urgently. Improvements in early diagnosis and more effective preventive treatments could affect such a decrease. Towards this end, we undertook for the first time an in-depth mass spectrometry-based quantitative shotgun proteomics study of non-invasively collected oral brush biopsies. Proteins isolated from brush biopsies from healthy normal tissue, oral premalignant lesion tissue (OPMLs), oral squamous cell carcinoma (OSCC) and matched control tissue were compared. In replicated proteomic datasets, the secretory leukocyte protease inhibitor (SLPI) protein stood out based on its decrease in abundance in both OPML and OSCC lesion tissues compared to healthy normal tissue. Western blotting in additional brushed biopsy samples confirmed a trend of gradual decreasing SLPI abundance between healthy normal and OPML tissue, with a larger decrease in OSCC lesion tissue. A similar SLPI decrease was observed in-vitro comparing model OPML and OSCC cell lines. In addition, exfoliated oral cells in patients’ whole saliva showed a loss of SLPI correlated with oral cancer progression. These results, combined with proteomics data indicating a decrease in SLPI in matched healthy control tissue from OSCC patients compared to tissue from healthy normal tissue, suggested a systemic decrease of SLPI in oral cells correlated with oral cancer development. Finally, in-vitro experiments showed that treatment with SLPI significantly decreased NF-kB activity in an OPML cell line. The findings indicate anti-inflammatory activity in OPML, supporting a mechanistic role of SLPI in OSCC progression and suggesting its potential for preventative treatment of at-risk oral lesions. Collectively, our results show for the first time the potential for SLPI as a mechanism-based, non-invasive biomarker of oral cancer progression with potential in preventive treatment.
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影响因子：
7
作者：
Ross, PL;Huang, YLN;Pappin, DJ
通讯作者：
Pappin, DJ
影响因子：
--
作者：
Caicedo-Granados, Emiro E.;Wuertz, Beverly R.;Ondrey, Frank G.
通讯作者：
Ondrey, Frank G.
影响因子：
3.4
作者：
Onsongo, Getiria;Stone, Matthew D.;Van Riper, Susan K.;Chilton, John;Wu, Baolin;Higgins, LeeAnn;Lund, Troy C.;Carlis, John V.;Griffin, Timothy J.
通讯作者：
Griffin, Timothy J.
影响因子：
2
作者：
Driemel, Oliver;Murzik, Ulrike;von Eggeling, Ferdinand
通讯作者：
von Eggeling, Ferdinand
影响因子：
4.8
作者：
Molinolo, Alfredo A.;Amornphimoltham, Panomwat;Squarize, Cristiane H.;Castilho, Rogerio M.;Patel, Vyomesh;Gutkind, J. Silvio
通讯作者：
Gutkind, J. Silvio