Use of Quantitative RT-PCR for Staging Esophageal Cancer

描述(申请人提供)：在美国，食管腺癌的发病率自1974年以来上升了350%以上，而长期存活率一直保持在10%-15%。目前的分期方法不足以预测这种疾病的存活率，事实证明，即使是早期的、有可能切除的肿瘤患者也经常复发和死亡。由于治疗选择是基于病理分期，临床医生需要改进的分期方法，以帮助为这些患者制定适当的治疗计划。我们以前发表的报告表明，食道癌患者的疾病复发和低生存率可能部分是由于存在淋巴结的隐匿性转移。然而，最近，比尔等人。《自然医学》杂志报道，原发肿瘤中的基因表达模式可以预测I期肺癌患者的预后。此外，《自然遗传学》和《柳叶刀与癌细胞》上的三篇新报告表明，转移倾向实际上可能是由原发肿瘤的基因表达模式编码的。此外，Huang等人在《柳叶刀》上的研究。确定了独立的基因组，似乎可以预测乳腺癌患者的淋巴转移和总体复发。因此，这些相互关联的事件似乎是通过对原发肿瘤的分析可以检测到的不同生物过程的结果。我们的假设是，原发肿瘤中的基因表达模式决定了食管腺癌患者的转移潜力和生存概率。随后，我们相信，对食道肿瘤的微阵列分析将使我们能够识别与转移和生存相关的基因集。鉴于食道癌的淋巴状态与生存率之间的相关性，我们还假设基因表达分析和隐匿性疾病检测方法将识别重叠的高复发风险患者组。在这项建议中，我们打算探索从原发肿瘤的微阵列分析获得的数据与隐匿性淋巴转移的分析之间的关系。我们相信，这一综合分子分期的结合将使我们能够显著改善目前食管腺癌的分期。此外，我们相信这项研究将回答一些关于食道癌的肿瘤生物学和转移的非常有趣的问题。

DESCRIPTION (provided by applicant): In the USA, the incidence of esophageal adenocarcinoma has risen more than 350% since 1974 while long-term survival rates have remained at 10-15%. Current staging methods are inadequate for predicting survival in this disease, as evidenced by the fact that even patients with early stage, potentially resectable tumors frequently recur and die. Since treatment options are based on pathologic stage, clinicians need improved staging methods to assist in appropriate treatment planning for these patients. Our previously published reports indicate that disease recurrence and poor survival in esophageal cancer patients may be predicted, in part, by the presence of occult metastases to lymph nodes. Recently however, Beer et al. reported in Nature Medicine that gene expression patterns in primary tumors can predict outcome in stage I lung cancer patients. In addition, three new reports in Nature Genetics and The Lancet and Cancer Cell demonstrate that the propensity to metastasize may actually be encoded in the gene expression patterns of primary tumors. Furthermore, the Lancet study by Huang et al. identified separate gene sets that seem to predict lymph node metastasis and overall recurrence in breast cancer patients. These interrelated events would thus appear to be the result of distinct biological processes that can be detected by analysis of the primary tumor. It is our hypothesis that gene expression patterns in the primary tumor determine metastatic potential and probability of survival for patients with esophageal adenocarcinoma. Subsequently, we believe that microarray analysis of esophageal tumors will allow us to identify sets of genes that correlate with both metastasis and survival. Given the correlation between lymph node status and survival in esophageal cancer, we also hypothesize that gene expression analysis and occult disease detection approaches will identify overlapping sets of patients at high risk for recurrence. In this proposal, we intend to explore the relationship between data obtained from microarray analysis of the primary tumors and analysis of occult lymph node involvement. We believe that the combination of this comprehensive molecular staging will allow us to significantly improve upon the current staging of esophageal adenocarcinoma. In addition, we believe that this research will answer some very interesting questions about tumor biology and metastasis in esophageal cancer.