Saglam Ozlen, Shah Veena, Worsham Maria J
Department of Pathology, Henry Ford Hospital, Detroit, MI, USA.
Diagn Mol Pathol. 2007 Dec;16(4):218-21. doi: 10.1097/PDM.0b013e3180d0aab5.
A current shortcoming in cancer prognostication and treatment is a lack of methods that adequately address the complexity and diversity of the disease. Prognostic marker systems based on single parameters have generally proven inadequate. Thus, multiparametric methods, which rely on many pieces of information, are ideally suited to the grouping of tumor subtypes and the identification of specific patterns of disease progression.
This study investigated, on an exploratory basis, whether genome wide alterations of loss and gain, using a panel of 122 gene probes (112 unique genes), discriminated between early stage (stage 1 and 2) and late stage (stage 3 and 4) laryngeal squamous cell carcinomas (LSCC). The LSCC cohort comprised 29 patients, 12 early and 17 late staged. Formalin-fixed LSCC DNA was interrogated by a genome wide candidate gene panel (122 genes) using the multiplex ligation-dependent probe amplification assay.
Statistical analysis employed the nonparametric Wilcoxon 2-sample test. Significant differences between tumor stages of early versus late were seen for the following genes: ERBB4, CASP2, RECQL4, and BCL7A. Loss of ERBB4 (P=0.045) and BCL7A (P=0.019) significantly discriminated between early and late stage LSCC. Gain of RECQL4 copy number (P=0.043) was associated with late LSCC. Gain of CASP2 (P=0.043) marked early LSCC, whereas loss was associated with late LSCC.
High-throughput genome wide approaches have the potential to yield discrete gene repertoires of early and late stage LSCC differentiation.
癌症预后和治疗目前的一个不足之处在于缺乏能够充分应对该疾病复杂性和多样性的方法。基于单一参数的预后标志物系统通常已被证明是不够的。因此，依赖多条信息的多参数方法非常适合肿瘤亚型的分组以及疾病进展特定模式的识别。
本研究基于探索性目的，调查使用一组122个基因探针（112个独特基因）进行全基因组缺失和增益改变是否能区分早期（1期和2期）和晚期（3期和4期）喉鳞状细胞癌（LSCC）。LSCC队列包括29例患者，其中12例为早期，17例为晚期。使用多重连接依赖探针扩增分析法，通过全基因组候选基因面板（122个基因）对福尔马林固定的LSCC DNA进行检测。
统计分析采用非参数Wilcoxon双样本检验。在以下基因中观察到早期与晚期肿瘤阶段之间存在显著差异：ERBB4、CASP2、RECQL4和BCL7A。ERBB4（P = 0.045）和BCL7A（P = 0.019）的缺失显著区分了早期和晚期LSCC。RECQL4拷贝数的增加（P = 0.043）与晚期LSCC相关。CASP2的增加（P = 0.043）标志着早期LSCC，而其缺失与晚期LSCC相关。
高通量全基因组方法有潜力产生早期和晚期LSCC分化的离散基因谱。
