A large-scale proteomics resource of circulating extracellular vesicles for biomarker discovery in pancreatic cancer
Pancreatic cancer has the worst prognosis of all common tumors. Earlier cancer diagnosis could increase survival rates and better assessment of metastatic disease could improve patient care. As such, there is an urgent need to develop biomarkers to diagnose this deadly malignancy. Analyzing circulat...
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eLife Sciences Publications Ltd
2024-12-01
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| Online Access: | https://elifesciences.org/articles/87369 |
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| author | Bruno Bockorny Lakshmi Muthuswamy Ling Huang Marco Hadisurya Christine Maria Lim Leo L Tsai Ritu R Gill Jesse L Wei Andrea J Bullock Joseph E Grossman Robert J Besaw Supraja Narasimhan Weiguo Andy Tao Sofia Perea Mandeep S Sawhney Steven D Freedman Manuel Hildago Anton Iliuk Senthil K Muthuswamy |
| author_facet | Bruno Bockorny Lakshmi Muthuswamy Ling Huang Marco Hadisurya Christine Maria Lim Leo L Tsai Ritu R Gill Jesse L Wei Andrea J Bullock Joseph E Grossman Robert J Besaw Supraja Narasimhan Weiguo Andy Tao Sofia Perea Mandeep S Sawhney Steven D Freedman Manuel Hildago Anton Iliuk Senthil K Muthuswamy |
| author_sort | Bruno Bockorny |
| collection | DOAJ |
| description | Pancreatic cancer has the worst prognosis of all common tumors. Earlier cancer diagnosis could increase survival rates and better assessment of metastatic disease could improve patient care. As such, there is an urgent need to develop biomarkers to diagnose this deadly malignancy. Analyzing circulating extracellular vesicles (cEVs) using ‘liquid biopsies’ offers an attractive approach to diagnose and monitor disease status. However, it is important to differentiate EV-associated proteins enriched in patients with pancreatic ductal adenocarcinoma (PDAC) from those with benign pancreatic diseases such as chronic pancreatitis and intraductal papillary mucinous neoplasm (IPMN). To meet this need, we combined the novel EVtrap method for highly efficient isolation of EVs from plasma and conducted proteomics analysis of samples from 124 individuals, including patients with PDAC, benign pancreatic diseases and controls. On average, 912 EV proteins were identified per 100 µL of plasma. EVs containing high levels of PDCD6IP, SERPINA12, and RUVBL2 were associated with PDAC compared to the benign diseases in both discovery and validation cohorts. EVs with PSMB4, RUVBL2, and ANKAR were associated with metastasis, and those with CRP, RALB, and CD55 correlated with poor clinical prognosis. Finally, we validated a seven EV protein PDAC signature against a background of benign pancreatic diseases that yielded an 89% prediction accuracy for the diagnosis of PDAC. To our knowledge, our study represents the largest proteomics profiling of circulating EVs ever conducted in pancreatic cancer and provides a valuable open-source atlas to the scientific community with a comprehensive catalogue of novel cEVs that may assist in the development of biomarkers and improve the outcomes of patients with PDAC. |
| format | Article |
| id | doaj-art-2fbf0bf62bc64eee832a7920b461d554 |
| institution | DOAJ |
| issn | 2050-084X |
| language | English |
| publishDate | 2024-12-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj-art-2fbf0bf62bc64eee832a7920b461d5542025-08-20T02:52:42ZengeLife Sciences Publications LtdeLife2050-084X2024-12-011210.7554/eLife.87369A large-scale proteomics resource of circulating extracellular vesicles for biomarker discovery in pancreatic cancerBruno Bockorny0https://orcid.org/0000-0002-9162-1560Lakshmi Muthuswamy1Ling Huang2https://orcid.org/0000-0001-8855-788XMarco Hadisurya3Christine Maria Lim4Leo L Tsai5Ritu R Gill6Jesse L Wei7Andrea J Bullock8Joseph E Grossman9Robert J Besaw10Supraja Narasimhan11Weiguo Andy Tao12https://orcid.org/0000-0002-5535-5517Sofia Perea13Mandeep S Sawhney14Steven D Freedman15Manuel Hildago16Anton Iliuk17https://orcid.org/0000-0002-2914-1363Senthil K Muthuswamy18https://orcid.org/0000-0001-6564-9634Division of Medical Oncology, Beth Israel Deaconess Medical Center, Boston, United States; Harvard Medical School, Boston, United StatesBlueprint Medicines, Cambridge, United StatesHenry Ford Cancer Institute, Detroit, United StatesDepartment of Biochemistry, Purdue University West Lafayette, West Lafayette, United StatesNanyang Technological University, Singapore, SingaporeHarvard Medical School, Boston, United States; Department of Radiology, Beth Israel Deaconess Medical Center, Boston, United StatesHarvard Medical School, Boston, United States; Department of Radiology, Beth Israel Deaconess Medical Center, Boston, United StatesHarvard Medical School, Boston, United States; Department of Radiology, Beth Israel Deaconess Medical Center, Boston, United StatesDivision of Medical Oncology, Beth Israel Deaconess Medical Center, Boston, United States; Harvard Medical School, Boston, United StatesAgenus Inc, Lexington, United StatesDivision of Medical Oncology, Beth Israel Deaconess Medical Center, Boston, United StatesDeciphera Pharmaceuticals, Waltham, United StatesDepartment of Biochemistry, Purdue University West Lafayette, West Lafayette, United StatesDivision of Medical Oncology, Beth Israel Deaconess Medical Center, Boston, United StatesHarvard Medical School, Boston, United States; Division of Gastroenterology, Beth Israel Deaconess Medical Center, Boston, United StatesHarvard Medical School, Boston, United States; Division of Gastroenterology, Beth Israel Deaconess Medical Center, Boston, United StatesDivision of Hematology-Oncology, Weill Cornell Medical College, New York, United States; New York-Presbyterian Hospital, New York, United StatesTymora Analytical Operations, West Lafayette, United StatesNational Cancer Institute, Bethesda, United StatesPancreatic cancer has the worst prognosis of all common tumors. Earlier cancer diagnosis could increase survival rates and better assessment of metastatic disease could improve patient care. As such, there is an urgent need to develop biomarkers to diagnose this deadly malignancy. Analyzing circulating extracellular vesicles (cEVs) using ‘liquid biopsies’ offers an attractive approach to diagnose and monitor disease status. However, it is important to differentiate EV-associated proteins enriched in patients with pancreatic ductal adenocarcinoma (PDAC) from those with benign pancreatic diseases such as chronic pancreatitis and intraductal papillary mucinous neoplasm (IPMN). To meet this need, we combined the novel EVtrap method for highly efficient isolation of EVs from plasma and conducted proteomics analysis of samples from 124 individuals, including patients with PDAC, benign pancreatic diseases and controls. On average, 912 EV proteins were identified per 100 µL of plasma. EVs containing high levels of PDCD6IP, SERPINA12, and RUVBL2 were associated with PDAC compared to the benign diseases in both discovery and validation cohorts. EVs with PSMB4, RUVBL2, and ANKAR were associated with metastasis, and those with CRP, RALB, and CD55 correlated with poor clinical prognosis. Finally, we validated a seven EV protein PDAC signature against a background of benign pancreatic diseases that yielded an 89% prediction accuracy for the diagnosis of PDAC. To our knowledge, our study represents the largest proteomics profiling of circulating EVs ever conducted in pancreatic cancer and provides a valuable open-source atlas to the scientific community with a comprehensive catalogue of novel cEVs that may assist in the development of biomarkers and improve the outcomes of patients with PDAC.https://elifesciences.org/articles/87369pancreatic cancerextracellular vesiclesbiomarkerpancreatitis |
| spellingShingle | Bruno Bockorny Lakshmi Muthuswamy Ling Huang Marco Hadisurya Christine Maria Lim Leo L Tsai Ritu R Gill Jesse L Wei Andrea J Bullock Joseph E Grossman Robert J Besaw Supraja Narasimhan Weiguo Andy Tao Sofia Perea Mandeep S Sawhney Steven D Freedman Manuel Hildago Anton Iliuk Senthil K Muthuswamy A large-scale proteomics resource of circulating extracellular vesicles for biomarker discovery in pancreatic cancer eLife pancreatic cancer extracellular vesicles biomarker pancreatitis |
| title | A large-scale proteomics resource of circulating extracellular vesicles for biomarker discovery in pancreatic cancer |
| title_full | A large-scale proteomics resource of circulating extracellular vesicles for biomarker discovery in pancreatic cancer |
| title_fullStr | A large-scale proteomics resource of circulating extracellular vesicles for biomarker discovery in pancreatic cancer |
| title_full_unstemmed | A large-scale proteomics resource of circulating extracellular vesicles for biomarker discovery in pancreatic cancer |
| title_short | A large-scale proteomics resource of circulating extracellular vesicles for biomarker discovery in pancreatic cancer |
| title_sort | large scale proteomics resource of circulating extracellular vesicles for biomarker discovery in pancreatic cancer |
| topic | pancreatic cancer extracellular vesicles biomarker pancreatitis |
| url | https://elifesciences.org/articles/87369 |
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