Proteomic analysis reveals successive aberrations in protein expression from healthy mucosa to invasive head and neck cancer
Proteomic analysis reveals successive aberrations in protein expression from healthy mucosa to invasive head and neck cancer
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DOI：
10.1038/sj.onc.1209770
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发表时间：
2007-01-04
期刊：
影响因子：
8
通讯作者：
Bosch, F. X.
中科院分区：
文献类型：
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作者：
Roesch-Ely, M.;Nees, M.;Bosch, F. X.
头颈部鳞状细胞癌(HNSCC)的发展是一个多步骤的过程，在许多情况下涉及一种被称为“野癌变”的现象。为了确定在肿瘤发生和癌变的不同阶段发生的蛋白表达的变化，我们在IMAC30蛋白质芯片阵列上用SELDI-TOF-MS分析了113个HNSCC和73个健康的、99个肿瘤远处的和18个肿瘤邻近的鳞状黏膜组织。48个蛋白质峰在正常粘膜和HNSCC中有差异表达。用质谱仪鉴定了Calgizarrin(S100A11)、半胱氨酸蛋白酶抑制剂Cystatin A、酰辅酶A结合蛋白、Stratifin(14-3-3sigma)、组蛋白H4、α-和β-血红蛋白、β-血红蛋白的C末端片段以及α-防御素1-3。免疫组织化学(IHC)证实，α-防御素的表达发生了不同程度的变化。监督预测分析显示，对于健康粘膜(正确分类94.5%)和肿瘤样本(正确分类92.9%)，分类效果很好。将该分类器应用于肿瘤邻近和肿瘤远处的粘膜样本，发现了巨大的变化：只有59.6%的肿瘤远处活检被归类为正常，27.3%被预测为异常或HNSCC。值得注意的是，72%的肿瘤旁粘膜被预测为异常。这些数据为转基因田地的存在提供了证据，这些田地的组织学并不明显。将32例患者的肿瘤远距离样本中的蛋白质谱与临床结果进行比较，发现异常谱与肿瘤复发事件显著相关(P=0.018；费舍尔精确检验，双尾)。我们得出的结论是蛋白质组学上的亲。LING结合蛋白质鉴定大大优于组织病理学诊断，并可能对临床结果和个性化风险评估具有显着的预测能力。
Development of head and necksquamous cell carcinoma (HNSCC) is a multistep process and in many cases involves a phenomenon coined 'field cancerization'. In order to identify changes in protein expression occurring at different stages of tumorigenesis and field cancerization, we analysed 113 HNSCCs and 73 healthy, 99 tumor-distant and 18 tumor-adjacent squamous mucosae by SELDI-TOF-MS on IMAC30 ProteinChip Arrays. Forty-eight protein peaks were differentially expressed between healthy mucosa and HNSCC. Calgizarrin (S100A11), the Cystein proteinase inhibitor Cystatin A, Acyl-CoA-binding protein, Stratifin (14-3-3 sigma), Histone H4, alpha- and beta-Hemoglobin, a C-terminal fragment of beta-hemoglobin and the alpha-defensins 1-3 were identified by mass spectrometry. The alpha-defensins showed various alterations in expression as validated by immunohistochemistry (IHC). Supervised prediction analysis revealed excellent classification of healthy mucosa (94.5% correctly classified) and tumor samples (92.9% correctly classified). Application of this classifier to the tumor-adjacent and tumor-distant mucosa samples disclosed dramatic changes: only 59.6% of the tumor-distant biopsies were classified as normal, 27.3% were predicted as aberrant or HNSCC. Strikingly, 72% of the tumor-adjacent mucosae were predicted as aberrant. These data provide evidence for the existence of genetically altered fields with inconspicuous histology. Comparison of the protein profiles in the tumor-distant-samples with clinical outcome of 32 patients revealed a significant association between aberrant profiles with tumor relapse events (P = 0.018; Fisher's exact test, two-tailed). We conclude that proteomic pro. ling in conjunction with protein identification greatly outperforms histopathological diagnosis and may have significant predictive power for clinical outcome and personalized risk assessment.