DNA methylation, Liquid Biopsy, and Pancreatic Cancer

项目概要/摘要 胰腺导管腺癌（PDAC）的总生存率为9%，PDAC的检出率很高， NCI的优先领域。只有10-20%的PDAC患者具有主要可切除的疾病，而50-20%的PDAC患者具有主要可切除的疾病。 60%的患者被诊断患有不可切除的疾病。新辅助化疗可能有益于 这些病人。通过计算机断层扫描对新辅助治疗背景下的PDAC患者进行疾病监测 (CT)或检测CA 19 -9水平。这些方法可能不精确，不能预测肿瘤负荷。 因此，需要开发敏感和特异的生物标志物来评估疾病负担并监测疾病的进展。 接受新辅助治疗的PDAC患者。最近我们发现异常的DNA甲基化 游离DNA的分析可能是一种有吸引力的液体活检方法，用于检测PDAC。客观 本提案的目的是验证我们的液体活检方法并证明其实用性。在目标1中，我们将验证 我们的甲基10生物标志物用于检测早期PDAC。在目标2中，我们研究我们的甲基 10种生物标志物可以检测胰腺癌患者的微小残留病变。在完成这些 研究，我们将验证和开发一种新的DNA甲基化生物标志物集， PDAC检测及其对PDAC治疗策略监测的临床意义 患者

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.