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首页> 外文学位 >Characterization of cervical and head and neck squamous cell carcinomas by proteomic analysis.
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Characterization of cervical and head and neck squamous cell carcinomas by proteomic analysis.

机译：通过蛋白质组学分析表征宫颈癌和头颈部鳞状细胞癌。

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摘要

Squamous cell carcinomas arising from various subsites within the head and neck (HNSCC), while histologically identical, have substantial differences in survival and recurrence rates. Controversy exists as to whether this reflects physical differences between subsites or fundamental molecular heterogeneity. In this study, we used two proteomic approaches to evaluate HNSCCs for differences in protein expression between oral cavity, oropharynx, larynx and hypopharynx subsites. A tissue microarray (TMA) was constructed consisting of 71 patients with HNSCC. This TMA was queried for expression of 4 cell-cycle and regulatory proteins chosen a priori for their known roles in cancer, using automated quantitative analysis (AQUA) of protein expression. Frozen tissue samples from 14 patients with histologically confirmed HNSCC were enriched for tumor and normal tissue by laser capture microdissection. Total protein was extracted, analyzed by 2D-difference gel electrophoresis (2D-DIGE) with saturation dye labeling, and evaluated for differential protein expression between subsites. AQUA analysis likewise revealed no difference between subsite for cyclin D1, p53, Rb, or p14 expression. Proteomic analysis was based on 28 gels (14 cancer, 14 adjacent normal) and 732 spots were identified as matching across >90% of gels. Statistical analysis detected no significant differences in protein expression between subsites. Observed differences in outcomes between HNSCCs from different subsites are unlikely to reflect differences in tumor biology between subsites. It is possible that the observed heterogeneity in clinical behavior among HNSCCs may be based on fundamental differences in carcinogenesis such as viral versus chemical carcinogenic insult.
机译：由头颈内的各个亚部位（HNSCC）引起的鳞状细胞癌，虽然在组织学上是相同的，但在生存率和复发率上却有实质性差异。关于这是否反映了亚位点之间的物理差异或基本分子异质性存在争议。在这项研究中，我们使用两种蛋白质组学方法评估HNSCCs在口腔，口咽，喉和下咽亚位点之间的蛋白表达差异。构建了由71名HNSCC患者组成的组织微阵列（TMA）。使用蛋白质定量自动分析（AQUA），查询该TMA的4种细胞周期和调控蛋白的表达，并优先选择其在癌症中的已知作用的调控蛋白。通过激光捕获显微切割术富集了14例经组织学证实为HNSCC的患者的冷冻组织样品，以检测肿瘤和正常组织。提取总蛋白，通过具有饱和染料标记的2D差异凝胶电泳（2D-DIGE）分析，并评估亚位点之间的差异蛋白表达。 AQUA分析同样显示出细胞周期蛋白D1，p53，Rb或p14表达的亚位点之间没有差异。蛋白质组学分析基于28种凝胶（14种癌症，14种邻近正常细胞），在超过90％的凝胶中鉴定出732个斑点。统计分析未发现亚位点之间蛋白质表达的显着差异。观察到的来自不同亚位点的HNSCC之间的预后差异不太可能反映亚位点之间的肿瘤生物学差异。在HNSCC中观察到的临床行为异质性可能是基于癌变的根本差异，例如病毒与化学致癌性损害。

著录项

  • 作者

    Merkley, Mark Asher.;

  • 作者单位

    Medical College of Georgia.;

  • 授予单位 Medical College of Georgia.;
  • 学科 Biology Molecular.
  • 学位 Ph.D.
  • 年度 2011
  • 页码 207 p.
  • 总页数 207
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 I3;
  • 关键词

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