Program in Epidemiology, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.
PLoS One. 2012;7(9):e46575. doi: 10.1371/journal.pone.0046575. Epub 2012 Sep 28.
Oral and oropharyngeal squamous cell carcinomas (OSCC) are among the most common cancers worldwide, with approximately 60% 5-yr survival rate. To identify potential markers for disease progression, we used Affymetrix U133 plus 2.0 arrays to examine the gene expression profiles of 167 primary tumor samples from OSCC patients, 58 uninvolved oral mucosae from OSCC patients and 45 normal oral mucosae from patients without oral cancer, all enrolled at one of the three University of Washington-affiliated medical centers between 2003 to 2008. We found 2,596 probe sets differentially expressed between 167 tumor samples and 45 normal samples. Among 2,596 probe sets, 71 were significantly and consistently up- or down-regulated in the comparison between normal samples and uninvolved oral samples and between uninvolved oral samples and tumor samples. Cox regression analyses showed that 20 of the 71 probe sets were significantly associated with progression-free survival. The risk score for each patient was calculated from coefficients of a Cox model incorporating these 20 probe sets. The hazard ratio (HR) associated with each unit change in the risk score adjusting for age, gender, tumor stage, and high-risk HPV status was 2.7 (95% CI: 2.0-3.8, p = 8.8E-10). The risk scores in an independent dataset of 74 OSCC patients from the MD Anderson Cancer Center was also significantly associated with progression-free survival independent of age, gender, and tumor stage (HR 1.6, 95% CI: 1.1-2.2, p = 0.008). Gene Set Enrichment Analysis showed that the most prominent biological pathway represented by the 71 probe sets was the Integrin cell surface interactions pathway. In conclusion, we identified 71 probe sets in which dysregulation occurred in both uninvolved oral mucosal and cancer samples. Dysregulation of 20 of the 71 probe sets was associated with progression-free survival and was validated in an independent dataset.
口腔和口咽鳞状细胞癌（OSCC）是全球最常见的癌症之一，约有 60%的患者五年生存率。为了确定疾病进展的潜在标志物，我们使用 Affymetrix U133 plus 2.0 阵列检查了 167 例 OSCC 患者的原发性肿瘤样本、58 例来自 OSCC 患者的未受影响的口腔黏膜样本和 45 例来自无口腔癌患者的正常口腔黏膜样本的基因表达谱，这些样本均于 2003 年至 2008 年期间在华盛顿大学附属的三个医疗中心之一招募。我们发现 167 个肿瘤样本与 45 个正常样本之间存在 2596 个探针集的差异表达。在 2596 个探针集中，有 71 个探针集在正常样本与未受影响的口腔样本以及未受影响的口腔样本与肿瘤样本之间的比较中显著且一致地上调或下调。Cox 回归分析显示，71 个探针集中的 20 个探针集与无进展生存率显著相关。每个患者的风险评分是从包含这 20 个探针集的 Cox 模型系数计算得出的。在调整年龄、性别、肿瘤分期和高危 HPV 状态后，每个风险评分单位变化的风险比（HR）为 2.7（95%CI：2.0-3.8，p=8.8E-10）。MD 安德森癌症中心的 74 例 OSCC 患者的独立数据集的风险评分也与无进展生存率显著相关，独立于年龄、性别和肿瘤分期（HR 1.6，95%CI：1.1-2.2，p=0.008）。基因集富集分析显示，71 个探针集所代表的最突出的生物学途径是整合素细胞表面相互作用途径。总之，我们在未受影响的口腔黏膜和癌症样本中均发现了 71 个探针集的失调。71 个探针集中的 20 个探针集的失调与无进展生存率相关，并在独立数据集得到验证。
