journal article·2017-11-28

Combining Machine Learning and Nanofluidic Technology To Diagnose Pancreatic Cancer Using Exosomes

Jina Ko, Neha Bhagwat, Stephanie S. Yee, Natalia Ortiz, Amine Sahmoud, Taylor Black, Nicole M. Aiello, Lydie McKenzie, Mark O’Hara, Colleen Redlinger, Janae Romeo, Erica L. Carpenter, Ben Z. Stanger, David Issadore

ACS Nano· Volume 11· Issue 11
Publisher page

Abstract

Circulating exosomes contain a wealth of proteomic and genetic information, presenting an enormous opportunity in cancer diagnostics. While microfluidic approaches have been used to successfully isolate cells from complex samples, scaling these approaches for exosome isolation has been limited by the low throughput and susceptibility to clogging of nanofluidics. Moreover, the analysis of exosomal biomarkers is confounded by substantial heterogeneity between patients and within a tumor itself. To address these challenges, we developed a multichannel nanofluidic system to analyze crude clinical samples. Using this platform, we isolated exosomes from healthy and diseased murine and clinical cohorts, profiled the RNA cargo inside of these exosomes, and applied a machine learning algorithm to generate predictive panels that could identify samples derived from heterogeneous cancer-bearing individuals. Using this approach, we classified cancer and precancer mice from healthy controls, as well as pancreatic cancer patients from healthy controls, in blinded studies.
Source: openalex_inverted_index · Quality: baseline

Research context

OpenAlex topics: Extracellular vesicles in disease · Nanopore and Nanochannel Transport Studies · MicroRNA in disease regulation

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Department of Bioengineering and ∥Department of Electrical and Systems Engineering, School of Engineering and Applied Sciences, University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States

Division of Gastroenterology and §Division of Hematology-Oncology, Department of Medicine, Perelman School of Medicine and ⊥Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States

Funding

Pennsylvania Department of Health · National Cancer Institute · National Institute of Diabetes and Digestive and Kidney Diseases · Hartwell Foundation · American Cancer Society · Pancreatic Cancer Action Network

References (64)

Show source-provided references
1. 10.1155/2014/47490510.1155/2014/474905 ↗
2. 10.1172/JCI4004510.1172/JCI40045 ↗
3. 10.1038/emboj.2012.13210.1038/emboj.2012.132 ↗
4. Mullerat J. · Anticancer Res. · 2002 · 23 · 2995
5. 10.1016/j.ygyno.2008.04.03810.1016/j.ygyno.2008.04.038 ↗
6. 10.1126/scitranslmed.300426110.1126/scitranslmed.3004261 ↗
7. 10.1039/C5AN01610J10.1039/C5AN01610J ↗
8. 10.1016/j.ygyno.2008.04.03310.1016/j.ygyno.2008.04.033 ↗
9. 10.1038/nm.299410.1038/nm.2994 ↗
10. 10.1038/nature1458110.1038/nature14581 ↗
11. 10.1038/ncb316910.1038/ncb3169 ↗
12. 10.1039/B916199F10.1039/B916199F ↗
13. 10.1002/0471143030.cb0322s3010.1002/0471143030.cb0322s30 ↗
14. 10.1073/pnas.101253910710.1073/pnas.1012539107 ↗
15. 10.1126/scitranslmed.300374710.1126/scitranslmed.3003747 ↗
16. 10.1073/pnas.050771910210.1073/pnas.0507719102 ↗
17. 10.1007/s10544-006-0033-010.1007/s10544-006-0033-0 ↗
18. 10.1038/nmeth.129010.1038/nmeth.1290 ↗
19. 10.3322/caac.2125410.3322/caac.21254 ↗
20. 10.1002/ijc.2825610.1002/ijc.28256 ↗
21. 10.1364/OL.11.00028810.1364/OL.11.000288 ↗
22. 10.1016/S0580-9517(10)37002-410.1016/S0580-9517(10)37002-4 ↗
23. 10.1016/j.jmmm.2010.05.04410.1016/j.jmmm.2010.05.044 ↗
24. 10.1038/nnano.2010.14810.1038/nnano.2010.148 ↗
25. 10.1016/j.bbagen.2012.03.01710.1016/j.bbagen.2012.03.017 ↗
26. 10.1038/nm.275310.1038/nm.2753 ↗
27. 10.1016/j.cell.2011.11.02510.1016/j.cell.2011.11.025 ↗
28. 10.1038/nature1121710.1038/nature11217 ↗
29. 10.1080/00031305.1983.1048308710.1080/00031305.1983.10483087 ↗
30. 10.1073/pnas.080979510510.1073/pnas.0809795105 ↗
31. 10.1039/C0LC00149J10.1039/C0LC00149J ↗
32. 10.1126/scitranslmed.300561610.1126/scitranslmed.3005616 ↗
33. 10.1172/JCI8113510.1172/JCI81135 ↗
34. 10.3390/s15051038010.3390/s150510380 ↗
35. 10.1007/978-3-319-41981-7_1010.1007/978-3-319-41981-7_10 ↗
36. 10.1039/c1lc20177h10.1039/c1lc20177h ↗
37. 10.1053/j.gastro.2004.03.05810.1053/j.gastro.2004.03.058 ↗
38. 10.1039/C6LC00487C10.1039/C6LC00487C ↗
39. Ethem, A.Introduction to machine learning;MIT Press:Cambridge, MA, 2014; p3.
40. 10.1016/j.urolonc.2011.04.00110.1016/j.urolonc.2011.04.001 ↗
41. 10.1002/adhm.20130050210.1002/adhm.201300502 ↗
42. 10.1101/gad.115870310.1101/gad.1158703 ↗
43. 10.1016/j.ccell.2015.09.01810.1016/j.ccell.2015.09.018 ↗
44. 10.1006/bbrc.2001.437710.1006/bbrc.2001.4377 ↗
45. Campagna D. · Int. J. Clin. Exp. Pathol · 2008 · 1 · 32
46. 10.1002/ijc.2236010.1002/ijc.22360 ↗
47. 10.1016/S0002-9440(10)63911-910.1016/S0002-9440(10)63911-9 ↗
48. Schek N. · Cancer Res. · 1988 · 48 · 6354
49. 10.1038/labinvest.2014.1010.1038/labinvest.2014.10 ↗
50. 10.1038/srep0763910.1038/srep07639 ↗
51. 10.1007/s13193-011-0042-110.1007/s13193-011-0042-1 ↗
52. 10.1007/s10620-011-1709-810.1007/s10620-011-1709-8 ↗
53. 10.1039/C3LC50580D10.1039/C3LC50580D ↗
54. 10.1371/journal.pone.017062810.1371/journal.pone.0170628 ↗
55. 10.3402/jev.v2i0.2067710.3402/jev.v2i0.20677 ↗
56. 10.1038/s41551-016-002110.1038/s41551-016-0021 ↗
57. 10.1038/s41551-017-005810.1038/s41551-017-0058 ↗
58. 10.3390/ijms14071424010.3390/ijms140714240 ↗
59. 10.3402/jev.v3.2691310.3402/jev.v3.26913 ↗
60. 10.1158/0008-5472.CAN-04-380410.1158/0008-5472.CAN-04-3804 ↗
61. 10.3402/jev.v3.2469210.3402/jev.v3.24692 ↗
62. 10.1016/j.jim.2014.06.00710.1016/j.jim.2014.06.007 ↗
63. 10.3402/jev.v2i0.2149410.3402/jev.v2i0.21494 ↗
64. 10.1039/C7LC00703E10.1039/C7LC00703E ↗