Proteomic alterations in early stage cervical cancer.
Proteomic alterations in early stage cervical cancer.
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DOI：
10.18632/oncotarget.24773
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发表时间：
2018-04-06
期刊：
影响因子：
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通讯作者：
Luider TM
中科院分区：
文献类型：
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作者：
Güzel C;Govorukhina NI;Wisman GBA;Stingl C;Dekker LJM;Klip HG;Hollema H;Guryev V;Horvatovich PL;van der Zee AGJ;Bischoff R;Luider TM
激光捕获显微切割（LCM）允许捕获组织中的细胞类型或明确定义的结构。我们以半定量的方式比较了来自鳞状细胞宫颈癌（SCC，n = 22）患者的8，000个肿瘤细胞与来自正常宫颈组织的健康上皮和基质细胞（n = 13）的蛋白质组。将蛋白质酶促消化成肽，通过高分辨率质谱法测量肽，并通过“全有或全无”分析、Bonferroni和Benjamini-Hochberg校正进行多重测试。通过比较LCM细胞类型制备物，基于以限制性“全有或全无”方式解决特异性的标准，与健康上皮和基质相比，仅在早期宫颈癌（n = 11）中发现31种蛋白质。通过Bonferroni校正多重检测，30种蛋白在早期宫颈癌和健康对照之间显著上调，包括MCM蛋白家族的6个成员。MCM蛋白参与DNA修复，预计将参与癌症的早期阶段。在对多次检测进行不太严格的Benjamini-Hochberg校正后，我们发现319种蛋白质的丰度在早期宫颈癌和健康对照之间存在显著差异。通过平行反应监测（PRM），在全组织裂解物中确认了四种蛋白质。通过排列校正多重检验的不稳定性通路分析导致两个网络在早期宫颈癌中与健康组织相比受到差异调节。从这些网络中，我们了解到特定的肿瘤机制在宫颈癌的早期阶段变得有效。
Laser capture microdissection (LCM) allows the capture of cell types or well-defined structures in tissue. We compared in a semi-quantitative way the proteomes from an equivalent of 8,000 tumor cells from patients with squamous cell cervical cancer (SCC, n = 22) with healthy epithelial and stromal cells obtained from normal cervical tissue (n = 13). Proteins were enzymatically digested into peptides which were measured by high-resolution mass spectrometry and analyzed by “all-or-nothing” analysis, Bonferroni, and Benjamini-Hochberg correction for multiple testing. By comparing LCM cell type preparations, 31 proteins were exclusively found in early stage cervical cancer (n = 11) when compared with healthy epithelium and stroma, based on criteria that address specificity in a restrictive “all-or-nothing” way. By Bonferroni correction for multiple testing, 30 proteins were significantly up-regulated between early stage cervical cancer and healthy control, including six members of the MCM protein family. MCM proteins are involved in DNA repair and expected to be participating in the early stage of cancer. After a less stringent Benjamini-Hochberg correction for multiple testing, we found that the abundances of 319 proteins were significantly different between early stage cervical cancer and healthy controls. Four proteins were confirmed in digests of whole tissue lysates by Parallel Reaction Monitoring (PRM). Ingenuity Pathway Analysis using correction for multiple testing by permutation resulted in two networks that were differentially regulated in early stage cervical cancer compared with healthy tissue. From these networks, we learned that specific tumor mechanisms become effective during the early stage of cervical cancer.