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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...

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Autores principales: Hinzman, Charles P, Bansal, Shivani, Li, Yaoxiang, Banerjee, Partha, Cheema, Amrita
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cambridge University Press 2020
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.
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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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