Detection and prognosis of early-stage pancreatic cancer by interdependent plasma markers

通过相互依赖的血浆标志物检测早期胰腺癌并预测预后

• 批准号: 10375662
• 负责人: Peter J Allen
• 金额: $ 37.46万
• 依托单位: VAN ANDEL RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-08-17 至 2023-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10375662
• 关键词: Area; Benign; Biological Markers; Biometry; Blinded; Cancer Control; Cancer Etiology; Cessation of life; Clinical; Collaborations; Complement; Data; Detection; Development; Disease; Early Diagnosis; Environment; Excision; Face; Gastrointestinal tract structure; Goals; Individual; Laboratories; Lead; Malignant Neoplasms; Malignant neoplasm of pancreas; Methods; Molecular; Operative Surgical Procedures; Outcome; Pancreas; Pancreatic Adenocarcinoma; Patients; Performance; Pharmaceutical Preparations; Plasma; Population; Positioning Attribute; Prevalence; Private Sector; Prognosis; Recovery; Research; Resectable; Resources; Risk; Sampling; Scientist; Sensitivity and Specificity; Specificity; Specimen; Technology; Testing; Therapeutic; Time; Training; Validation; accurate diagnosis; base; biomarker panel; candidate marker; design; experience; improved; improved outcome; member; optimal treatments; pancreatic cancer patients; predictive marker; progression marker; public health relevance; response; success; trend; validation studies

 DESCRIPTION (provided by applicant): Pancreatic cancer is alone among the major cancers in its increasing prevalence, and it is predicted to be the second-leading cause of cancer death by 2030. A strategy to help reverse this trend is to identify and treat more pancreatic cancers at an early stage of the disease, when surgery and therapeutics are most effective. Currently no biomarker is good enough to be used for the detection of early-stage disease in people at elevated risk for pancreatic cancer. In our preliminary research, we have developed biomarkers a) that have better sensitivity and specificity for early-stage cancer than the current best biomarker for pancreatic cancer, CA 19-9, and b) that can detect cancers that are low in CA 19-9. The several individual biomarkers complement each other because each is elevated in distinct groups of patients. These encouraging results lead us to propose that a biomarker panel developed from these and related biomarkers will provide the necessary performance to enable clinical detection and diagnosis of early-stage pancreatic cancer. A second strategy for improving outcomes is to better identify those early-stage cancers that will rapidly progress. Some cancers that appear to be early-stage and resectable show progression within a short time after surgery. Biomarkers to identify such cancers would allow better treatment for those patients, as they could be spared the risk and recovery time of surgery and immediately begin the appropriate systemic treatment, likely leading to better results. Currently, we have no accurate indicators of rapid progression after surgery. One of the biomarkers discovered in our preliminary research is elevated in most patients who have rapid progression after surgery, suggesting the possibility of its use as a progression biomarker. Our goal is to develop biomarkers that will be effective for detecting early-stage pancreatic cancer (Aim 1) and for identifying the early-stage cancers that will rapidly progress (Aim 2). We will pursue this goal by optimizing the existing biomarkers and bolstering them with additional biomarkers, and by developing, testing, and validating panels of biomarkers that improve performance over the individual biomarkers. We hypothesize that the biomarker panels can achieve the performance required for further clinical validation. We are in a good position to achieve our goal, given the promising biomarkers already discovered and the convergence of all the other factors necessary for a successful project: we have assembled a team of top experts in the clinical, technological, and statistical fields, plus we have the sample resources, patient base, experimental methods, institutional environment and support, and passion as a team to deliver high-impact results.

 描述（由适用提供）：胰腺癌仅在其越来越多的患病率上是主要的癌症之一，预计到2030年，它将成为癌症死亡的第二个主要原因。一种有助于扭转这种趋势的策略是在手术和疗法的早期疾病的早期阶段识别和治疗更多的胰腺癌。目前，没有生物标志物足够好，可以用于检测胰腺癌风险升高的人的早期疾病。在我们的初步研究中，我们开发了生物标志物a）对早期癌症的敏感性和特异性比当前的胰腺癌最佳生物标志物具有更好的敏感性和特异性。几种单独的生物标志物相互补充，因为在不同的患者组中均升高。这些令人鼓舞的结果使我们提出，由这些和相关的生物标志物开发的生物标志物小组将提供必要的性能，以实现早期胰腺癌的临床检测和诊断。改善结果的第二种策略是更好地识别那些将快速进步的早期癌症。一些似乎是早期且可切除的癌症在手术后的短时间内表现出进展。生物标志物可以识别这种癌症可以为这些患者提供更好的治疗，因为它们可能会保留手术的风险和恢复时间，并立即开始适当的全身治疗，可能会导致更好的结果。目前，我们没有准确的手术后快速进展指标。在我们的初步研究中发现的生物标志物之一是大多数手术后快速进展的患者的升高，这表明将其用作进展生物标志物的可能性。我们的目标是开发可有效检测早期胰腺癌的生物标志物（AIM 1）并确定将快速进步的早期癌症（AIM 2）。我们将通过 优化现有的生物标志物并使用其他生物标志物，并通过开发，测试和验证生物标志物的面板，以改善各个生物标志物的性能。我们假设生物标志物面板可以实现进一步的临床验证所需的性能。鉴于已经发现的Promise生物标志物以及成功项目所需的所有其他因素的融合：我们已经组建了一个临床，技术和统计领域的顶级专家团队，而且我们还拥有样本资源，患者基础，实验性方法，机构环境和支持者的热情来提供高级影响。

项目成果

Combined Analysis of Multiple Glycan-Array Datasets: New Explorations of Protein-Glycan Interactions.

• DOI: 10.1021/acs.analchem.1c01739
• 发表时间: 2021-08-10
• 期刊: Analytical chemistry
• 影响因子: 7.4
• 作者: Klamer Z;Haab B
• 通讯作者: Haab B

Overweight or Obese Individuals at Eighteen Years of Age Develop Pancreatic Adenocarcinoma at a Significantly Earlier Age.

• DOI: 10.1155/2018/2380596
• 发表时间: 2018
• 期刊: Gastroenterology research and practice
• 影响因子: 2
• 作者: Chao DT;Shah NH;Zeh HJ 3rd;Singhi AD;Bahary N;McGrath KM;Fasanella KE;Zureikat AH;Whitcomb DC;Brand RE
• 通讯作者: Brand RE

Biomarkers and Strategy to Detect Preinvasive and Early Pancreatic Cancer: State of the Field and the Impact of the EDRN.

• DOI: 10.1158/1055-9965.epi-20-0161
• 发表时间: 2020-12
• 期刊: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
• 作者: Liu Y;Kaur S;Huang Y;Fahrmann JF;Rinaudo JA;Hanash SM;Batra SK;Singhi AD;Brand RE;Maitra A;Haab BB
• 通讯作者: Haab BB

The CA19-9 and Sialyl-TRA Antigens Define Separate Subpopulations of Pancreatic Cancer Cells.

• DOI: 10.1038/s41598-017-04164-z
• 发表时间: 2017-06-22
• 期刊: Scientific reports
• 影响因子: 4.6
• 作者: Barnett D;Liu Y;Partyka K;Huang Y;Tang H;Hostetter G;Brand RE;Singhi AD;Drake RR;Haab BB
• 通讯作者: Haab BB

Operative drainage following pancreatic resection: analysis of 1122 patients resected over 5 years at a single institution.

• DOI: 10.1097/sla.0b013e3182813806
• 发表时间: 2013-12
• 期刊: Annals of surgery
• 影响因子: 9
• 作者: Correa-Gallego C;Brennan MF;Dʼangelica M;Fong Y;Dematteo RP;Kingham TP;Jarnagin WR;Allen PJ
• 通讯作者: Allen PJ