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4287 Extracellular vesicles as biomarkers for early detection of pancreatic cancer
OBJECTIVES/GOALS: Pancreatic ductal adenocarcinoma (PDAC) is projected to become the second leading cause of cancer-related deaths by 2030. Though many other cancers have seen improvements in patient survival rates, patients diagnosed with PDAC have a 5-year survival rate of only ~9%. A major contri...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Cambridge University Press
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8823425/ http://dx.doi.org/10.1017/cts.2020.67 |
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author | Hinzman, Charles P Bansal, Shivani Li, Yaoxiang Banerjee, Partha Cheema, Amrita |
author_facet | Hinzman, Charles P Bansal, Shivani Li, Yaoxiang Banerjee, Partha Cheema, Amrita |
author_sort | Hinzman, Charles P |
collection | PubMed |
description | OBJECTIVES/GOALS: Pancreatic ductal adenocarcinoma (PDAC) is projected to become the second leading cause of cancer-related deaths by 2030. Though many other cancers have seen improvements in patient survival rates, patients diagnosed with PDAC have a 5-year survival rate of only ~9%. A major contributor to decreased survival is late-stage diagnosis of the disease. New methods of early detection are urgently needed. Extracellular vesicles (EVs) are secreted from cells of all tissue types into the circulation. EVs play important roles in a variety of diseases. They have shown to promote cancer progression and they are being studied as potential biomarkers for disease diagnosis. The purpose of this study was to perform qualitative and quantitative characterization of small-molecule profiles of EVs derived from various pancreatic cancer (PC) and normal pancreas cell lines, to provide proof-of-concept for evaluating the efficacy of leveraging EVs as potential biomarkers of PDAC. METHODS/STUDY POPULATION: EVs were isolated from the conditioned media of six PC and two normal pancreas cell lines using differential ultracentrifugation with filtration. EV enrichment was validated using quantitative ELISA, immunoblot and transmission electron microscopy. Targeted liquid chromatography coupled to mass spectrometry (LC-MS/MS) and untargeted (UPLC-QTOF-MS) metabolomics were used to analyze the biochemical composition of EVs. RESULTS/ANTICIPATED RESULTS: The biochemical profile of PC EVs was found to be significantly different from the profiles of normal cell EVs. Interestingly, amino acids were downregulated in PC EVs as compared to normal cell EVs. However, PC EVs were enriched in lactate and malate. PC EVs also had significant upregulation in other small molecules such as xanthosine, guanosine diphosphate and nicotinamide. DISCUSSION/SIGNIFICANCE OF IMPACT: Our results indicate that the biochemical characterization of EVs using metabolomics has the potential to yield biomarkers which can delineate cancer cell-derived EVs from normal cell-derived EVs. Further work will test the clinical significance of these findings by similar analyses of plasma of PDAC patients. Furthermore, these profiles may be detectable before progression of the disease to late-stage PDAC, leading to the development of assays for earlier diagnosis in patients. |
format | Online Article Text |
id | pubmed-8823425 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Cambridge University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-88234252022-02-18 4287 Extracellular vesicles as biomarkers for early detection of pancreatic cancer Hinzman, Charles P Bansal, Shivani Li, Yaoxiang Banerjee, Partha Cheema, Amrita J Clin Transl Sci Basic Science/Methodology OBJECTIVES/GOALS: Pancreatic ductal adenocarcinoma (PDAC) is projected to become the second leading cause of cancer-related deaths by 2030. Though many other cancers have seen improvements in patient survival rates, patients diagnosed with PDAC have a 5-year survival rate of only ~9%. A major contributor to decreased survival is late-stage diagnosis of the disease. New methods of early detection are urgently needed. Extracellular vesicles (EVs) are secreted from cells of all tissue types into the circulation. EVs play important roles in a variety of diseases. They have shown to promote cancer progression and they are being studied as potential biomarkers for disease diagnosis. The purpose of this study was to perform qualitative and quantitative characterization of small-molecule profiles of EVs derived from various pancreatic cancer (PC) and normal pancreas cell lines, to provide proof-of-concept for evaluating the efficacy of leveraging EVs as potential biomarkers of PDAC. METHODS/STUDY POPULATION: EVs were isolated from the conditioned media of six PC and two normal pancreas cell lines using differential ultracentrifugation with filtration. EV enrichment was validated using quantitative ELISA, immunoblot and transmission electron microscopy. Targeted liquid chromatography coupled to mass spectrometry (LC-MS/MS) and untargeted (UPLC-QTOF-MS) metabolomics were used to analyze the biochemical composition of EVs. RESULTS/ANTICIPATED RESULTS: The biochemical profile of PC EVs was found to be significantly different from the profiles of normal cell EVs. Interestingly, amino acids were downregulated in PC EVs as compared to normal cell EVs. However, PC EVs were enriched in lactate and malate. PC EVs also had significant upregulation in other small molecules such as xanthosine, guanosine diphosphate and nicotinamide. DISCUSSION/SIGNIFICANCE OF IMPACT: Our results indicate that the biochemical characterization of EVs using metabolomics has the potential to yield biomarkers which can delineate cancer cell-derived EVs from normal cell-derived EVs. Further work will test the clinical significance of these findings by similar analyses of plasma of PDAC patients. Furthermore, these profiles may be detectable before progression of the disease to late-stage PDAC, leading to the development of assays for earlier diagnosis in patients. Cambridge University Press 2020-07-29 /pmc/articles/PMC8823425/ http://dx.doi.org/10.1017/cts.2020.67 Text en © The Association for Clinical and Translational Science 2020 https://creativecommons.org/licenses/by/4.0/This is an Open Access article, distributed under the terms of the Creative Commons Attribution licence (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted re-use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Basic Science/Methodology Hinzman, Charles P Bansal, Shivani Li, Yaoxiang Banerjee, Partha Cheema, Amrita 4287 Extracellular vesicles as biomarkers for early detection of pancreatic cancer |
title | 4287 Extracellular vesicles as biomarkers for early detection of pancreatic cancer |
title_full | 4287 Extracellular vesicles as biomarkers for early detection of pancreatic cancer |
title_fullStr | 4287 Extracellular vesicles as biomarkers for early detection of pancreatic cancer |
title_full_unstemmed | 4287 Extracellular vesicles as biomarkers for early detection of pancreatic cancer |
title_short | 4287 Extracellular vesicles as biomarkers for early detection of pancreatic cancer |
title_sort | 4287 extracellular vesicles as biomarkers for early detection of pancreatic cancer |
topic | Basic Science/Methodology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8823425/ http://dx.doi.org/10.1017/cts.2020.67 |
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