Principal Investigator

Ru
Chen
Awardee Organization

Baylor College Of Medicine
United States

Fiscal Year
2018
Activity Code
R01
Project End Date

Early detection of pancreatic cancer in diabetics

Pancreatic cancer is a highly lethal disease that is very difficult to diagnose. The high mortality of this disease is predominantly due to the advanced stage of disease at the time of diagnosis and a lack of effective treatments. Due to the low prevalence of pancreatic cancer (0.01%), early detection would be most cost-effective in screening increased-risk populations, such as new-onset type-2 diabetics. Clinical and research studies have substantiated the link between pancreatic cancer and new-onset type-2 diabetes. Development of a highly accurate blood-based test to detect pancreatic cancer in this population would represent a breakthrough in early detection of pancreatic cancer. Such a blood test, if used on an annual basis in this higher-risk population, could serve as an effective and inexpensive method for initial targeted screening. In this project, we proposed to develop and characterize a blood-based proteomics signature that allows early detection of pancreatic cancer patients with new-onset diabetics. The Specific Aims are as follows: Specific Aim 1: unbiased global discovery of differential proteins associated with pancreatic cancer in the blood of diabetic patients using quantitative proteomics; Specific Aim 2: development of targeted proteomics assay for 35 selected biomarker candidates; Specific Aim 3: establishment of a proteomics signature (biomarker panel) for detecting early stage pancreatic cancer in diabetic patients; Specific Aim 4: evaluation of the proteomics signature in detecting pancreatic cancer in asymptomatic patients. This proposal builds on our decade-long systematic study of pancreatic tumorigenesis, the rich resource of previous discoveries in pancreatic cancer biomarker development, well-characterized study cohorts from different institutions, as well as cutting-edge proteomics platform technologies that we have developed and implemented. Successful development of a blood-based assay to facilitate the early detection of pancreatic cancer for diabetic patients would alleviate the current prolonged work-up of higher-risk populations and provide critically important interception opportunities to treat earlier stage cancer.

Publications

  • Peng H, Pan S, Yan Y, Brand RE, Petersen GM, Chari ST, Lai LA, Eng JK, Brentnall TA, Chen R. Systemic Proteome Alterations Linked to Early Stage Pancreatic Cancer in Diabetic Patients. Cancers. 2020 Jun 11;12. (6). PMID: 32545216
  • Pan S, Chen R. Pathological implication of protein post-translational modifications in cancer. Molecular aspects of medicine. 2022 Aug;86:101097. Epub 2022 Apr 7. PMID: 35400524
  • Pan S, Lai LA, Simeone DM, Dawson DW, Yan Y, Crnogorac-Jurcevic T, Chen R, Brentnall TA. Proteomes of Extracellular Vesicles From Pancreatic Cancer Cells and Cancer-Associated Fibroblasts. Pancreas. 2022 Aug 1;51(7):790-799. PMID: 36395405
  • Chen R, Dawson DW, Pan S, Ottenhof NA, de Wilde RF, Wolfgang CL, May DH, Crispin DA, Lai LA, Lay AR, Waghray M, Wang S, McIntosh MW, Simeone DM, Maitra A, Brentnall TA. Proteins associated with pancreatic cancer survival in patients with resectable pancreatic ductal adenocarcinoma. Laboratory investigation; a journal of technical methods and pathology. 2015 Jan;95(1):43-55. Epub 2014 Oct 27. PMID: 25347153
  • Chen R, Pan S. Increased neutrophil infiltration as a body-wide effect in pancreatic cancer development. EBioMedicine. 2022 Jul;81:104089. Epub 2022 Jun 2. PMID: 35665683
  • Nigjeh EN, Chen R, Brand RE, Petersen GM, Chari ST, von Haller PD, Eng JK, Feng Z, Yan Q, Brentnall TA, Pan S. Quantitative Proteomics Based on Optimized Data-Independent Acquisition in Plasma Analysis. Journal of proteome research. 2017 Feb 3;16(2):665-676. Epub 2017 Jan 3. PMID: 27995795
  • Pan S, Brentnall TA, Chen R. Proteome alterations in pancreatic ductal adenocarcinoma. Cancer letters. 2020 Jan 28;469:429-436. Epub 2019 Nov 14. PMID: 31734355
  • Peng H, Chen R, Brentnall TA, Eng JK, Picozzi VJ, Pan S. Predictive proteomic signatures for response of pancreatic cancer patients receiving chemotherapy. Clinical proteomics. 2019 Jul 17;16:31. doi: 10.1186/s12014-019-9251-3. eCollection 2019. PMID: 31346328
  • Pan S, Brentnall TA, Chen R. Proteomics analysis of bodily fluids in pancreatic cancer. Proteomics. 2015 Aug;15(15):2705-15. Epub 2015 Apr 27. PMID: 25780901
  • Chen R, Lai LA, Sullivan Y, Wong M, Wang L, Riddell J, Jung L, Pillarisetty VG, Brentnall TA, Pan S. Disrupting glutamine metabolic pathways to sensitize gemcitabine-resistant pancreatic cancer. Scientific reports. 2017 Aug 11;7(1):7950. PMID: 28801576
  • Pan S, Chen R. Metaproteomic analysis of human gut microbiome in digestive and metabolic diseases. Advances in clinical chemistry. 2020;97:1-12. Epub 2020 Feb 17. PMID: 32448430
  • Nigjeh EN, Chen R, Allen-Tamura Y, Brand RE, Brentnall TA, Pan S. Spectral library-based glycopeptide analysis-detection of circulating galectin-3 binding protein in pancreatic cancer. Proteomics. Clinical applications. 2017 Sep;11. (9-10). Epub 2017 Jul 10. PMID: 28627758
  • Senavirathna L, Ma C, Chen R, Pan S. Proteomic Investigation of Glyceraldehyde-Derived Intracellular AGEs and Their Potential Influence on Pancreatic Ductal Cells. Cells. 2021 Apr 24;10. (5). PMID: 33923186
  • Senavirathna L, Ma C, Chen R, Pan S. Spectral Library-Based Single-Cell Proteomics Resolves Cellular Heterogeneity. Cells. 2022 Aug 7;11. (15). PMID: 35954294
  • Pan S, Brentnall TA, Chen R. Glycoproteins and glycoproteomics in pancreatic cancer. World journal of gastroenterology. 2016 Nov 14;22(42):9288-9299. PMID: 27895417
  • Senavirathna L, Pan S, Chen R. Protein Advanced Glycation End Products and Their Implications in Pancreatic Cancer. Cancer prevention research (Philadelphia, Pa.). 2023 Nov 1;16(11):601-610. PMID: 37578815