Early Detection of Pancreatic Cancer

项目简介：胰腺癌（PaC）是一种毁灭性的、鲜为人知的癌症。2005年，预计将诊断出32 180例新的胰腺腺癌病例，其中31 800例预计将死于这种疾病。胰腺癌的症状包括体重减轻、厌食、上腹部不适和背部疼痛，这些症状都是非特异性和模糊的，因此诊断可能会大大延迟。因此，不到20%的患者在做出诊断时患有可切除的疾病。因此，目前PaC最迫切的需求之一是制定一种合理的、以证据为基础的策略来筛查早期PaC。拟议研究的目的是确定有助于早期胰腺癌诊断的新型生物标志物。为了实现这一目标，我们组建了一支强大的研究团队，其中包括具有丰富蛋白质组学和生物统计学专业知识经验的基础科学家，以及对胰腺癌早期检测和治疗特别感兴趣的外科肿瘤学家的临床技能。最先进的二维液相色谱系统将用于制备可切除PaC患者和对照组（包括良性胰腺疾病患者、其他胃肠道恶性肿瘤患者和健康个体）的血清蛋白谱。由一组生物标志物组成的分类模型，可以正确地将PaC患者的血清与对照组进行分类，将从蛋白质谱中得出，并使用一组独立的血清蛋白质谱进行验证。组成生物标志物面板的单个蛋白质将通过串联质谱法进行鉴定。这些潜在的诊断性生物标志物的血清水平变化也将在PaC患者胰腺切除术后收集的血清中进行监测。使用尖端的蛋白质组学技术，我们期望鉴定出一组生物标志物，可用于这种毁灭性疾病的早期检测；从而使我们能够迅速推进我们的基础科学发现转化为临床。相关性：目前，没有可靠的筛查试验可用于胰腺癌的早期诊断。由于手术切除是治疗胰腺癌的唯一方法，因此迫切需要更好的方法在早期、可手术的阶段发现这种疾病。在这项研究中，我们将使用最先进的技术来鉴定血清中的蛋白质，这些蛋白质可能用于胰腺癌的早期检测，从而对该疾病患者的诊断和治疗产生深远的影响。

DESCRIPTION (provided by applicant): Project Summary: Pancreatic cancer (PaC) is a devastating and poorly understood cancer. In the year 2005, an estimated 32,180 new cases of pancreatic adenocarcinoma are projected to be diagnosed, of which 31,800 are expected to die from this disease. Symptoms of pancreatic carcinoma including weight loss, anorexia, epigastric discomfort, and back pain are non-specific and vague, so diagnosis may be considerably delayed. Consequently fewer than 20% of patients have resectable disease by the time the diagnosis is made. Thus, among the most compelling needs for PaC today is to develop a rational, evidence-based strategy to screen for early PaC. The purpose of the proposed studies is to identify novel biomarkers that will aid in the diagnosis of early pancreatic cancer. Towards this goal we have assembled a strong investigative team that includes basic scientists with extensive experience in proteomics and biostatistical expertise combined with the clinical skills of surgical oncologists with a particular interest in early detection and treatment of pancreatic cancer. A state-of-the-art two-dimensional liquid chromatography system will be used to prepare serum protein profiles from patients with resectable PaC and control subjects that include patients with benign pancreatic disease, other gastrointestinal malignancies, and healthy individuals. Classification models comprised of a panel of biomarkers that can correctly classify PaC patient serum from controls will be derived from the protein profiles and verified using an independent set of serum protein profiles. The individual proteins composing the panel of biomarkers will then be identified by tandem mass spectrometry. Changes in the serum level of these potential diagnostic biomarkers will also be monitored in serum collected postoperatively from patients who have undergone pancreatic resection for PaC. Using cutting-edge proteomic technologies, we anticipate the identification of a panel of biomarkers that may be used for early detection of this devastating disease; thus allowing us to rapidly advance the translation of our basic science findings into the clinic. Relevance: Currently, there are no reliable screening tests available for early diagnosis of pancreatic cancer. As surgical resection is the only curative intervention for pancreatic cancer, there is a desperate need for better methods of detection of this disease at an early, operable stage. In this study, we will use state-of-the- art technologies to identify proteins in serum that may be used for early detection of pancreatic cancer and thus have a profound impact upon the diagnosis and treatment of patients with this disease.