DNA methylation, Liquid Biopsy, and Pancreatic Cancer

项目摘要/摘要 胰腺导管腺癌(PDAC)，总体生存率为9%，且PDAC的检出率较高 NCI的优先领域。只有10%-20%的PDAC患者有一种主要可切除的疾病，而50%- 60%的患者被诊断为不能切除的疾病。新辅助化疗可能有益于 这些病人。新辅助环境下PDAC患者疾病监测的计算机断层扫描 (CT)或检测CA19-9水平。这些方法可能是不准确的，也不能预测肿瘤负担。 因此，有必要开发敏感和特异的生物标志物来评估疾病负担和监测 接受新辅助治疗的PDAC患者。最近我们发现异常的DNA甲基化 无细胞DNA分析可能是检测PDAC的一种有吸引力的液体活检方法。目标是 这项建议的目的是验证我们的液体活组织检查方法，并证明其有效性。在目标1中，我们将验证 我们的甲基10生物标记物可用于检测早期PDAC。在Aim，2中，我们调查了我们的甲基 10个生物标志物可以检测胰腺癌患者的微小残留病。在完成这些操作后 研究中，我们将验证和开发一种新的DNA甲基化生物标记集，该集在 PDAC的检测及其对监测治疗策略的临床意义 病人。

PROJECT SUMMARY/ABSTRACT Pancreatic ductal adenocarcinoma (PDAC), has an overall survival rate of 9%, and detection of PDAC is a high priority area for the NCI. Only 10-20% of patients with PDAC have a primarily resectable disease, while 50- 60% of patients are diagnosed with irresectable disease. Neoadjuvant chemotherapy maybe beneficial to these patients. Disease monitoring of PDAC patients in the neoadjuvant setting is by Computed tomography (CT) or detection of CA19-9 levels. These approaches can be imprecise and not predictive of tumor burden. Thus, there is a need to develop sensitive and specific biomarkers to assess disease burden and monitor patients with PDAC undergoing neoadjuvant therapy. Recently we showed that aberrant DNA methylation analysis in cell-free DNA may be an attractive liquid biopsy approach for the detection of PDAC. The objective of this proposal is to validate our liquid biopsy approach and demonstrate its utility. In Aim 1, we will validate our Methyl 10 biomarkers for the detection of early-stage PDAC. In Aim, 2, we investigate whether our Methyl 10 biomarkers can detect minimal residual disease in pancreatic cancer patients. At the completion of these studies, we will have validated and developed a novel DNA methylation biomarker set that is highly robust in the detection of PDAC and highlight its clinical significance for monitoring treatment strategies in PDAC patients.