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Cited by 649

The DOI matches its Crossref record; 17 of the 17 references it cites were found in a registry or an index.

Elevation of circulating branched-chain amino acids is an early event in human pancreatic adenocarcinoma development

Open access
Mayers, Jared R, Wu, Chen, Clish, Clary B, Kraft, Peter, Torrence, Margaret E, Fiske, Brian P, Yuan, Chen, Bao, Ying, Townsend, Mary K, Tworoger, Shelley S, Davidson, Shawn M, Papagiannakopoulos, Thales, Yang, Annan, Dayton, Talya L, Ogino, Shuji, Stampfer, Meir J, Giovannucci, Edward L, Qian, Zhi Rong, Rubinson, Douglas A, Ma, Jing, Sesso, Howard D, Gaziano, John M, Cochrane, Barbara B, Liu, Simin, Wactawski-Wende, Jean, Manson, JoAnn E, Pollak, Michael N, Kimmelman, Alec C, Souza, Amanda, Pierce, Kerry, Wang, Thomas J, Gerszten, Robert E, Fuchs, Charles S, Vander Heiden, Matthew G, Wolpin, Brian M·2014·Nature Medicine
DOI 10.1038/nm.3686
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Abstract

Most patients with pancreatic ductal adenocarcinoma (PDAC) are diagnosed with advanced disease and survive less than 12 months. PDAC has been linked with obesity and glucose intolerance, but whether changes in circulating metabolites are associated with early cancer progression is unknown. To better understand metabolic derangements associated with early disease, we profiled metabolites in prediagnostic plasma from individuals with pancreatic cancer (cases) and matched controls from four prospective cohort studies. We find that elevated plasma levels of branched-chain amino acids (BCAAs) are associated with a greater than twofold increased risk of future pancreatic cancer diagnosis. This elevated risk was independent of known predisposing factors, with the strongest association observed among subjects with samples collected 2 to 5 years before diagnosis, when occult disease is probably present. We show that plasma BCAAs are also elevated in mice with early-stage pancreatic cancers driven by mutant Kras expression but not in mice with Kras-driven tumors in other tissues, and that breakdown of tissue protein accounts for the increase in plasma BCAAs that accompanies early-stage disease. Together, these findings suggest that increased whole-body protein breakdown is an early event in development of PDAC.

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Authors
Mayers, J. R., Wu, C., Clish, C. B., Kraft, P., Torrence, M. E., Fiske, B. P., Yuan, C., Bao, Y., Townsend, M. K., Tworoger, S. S., Davidson, S. M., Papagiannakopoulos, T., Yang, A., Dayton, T. L., Ogino, S., Stampfer, M. J., Giovannucci, E. L., Qian, Z. R., Rubinson, D. A., Ma, J., Sesso, H. D., Gaziano, J. M., Cochrane, B. B., Liu, S., Wactawski-Wende, J., Manson, J. E., Pollak, M. N., Kimmelman, A. C., Souza, A., Pierce, K., Wang, T. J., Gerszten, R. E., Fuchs, C. S., Vander Heiden, M. G., & Wolpin, B. M.
Venue
Nature Medicine
Publisher
Springer Science and Business Media LLC
Published
2014-09-28
Volume
20
Issue
10
Pages
1193-1198
ISSN
  • 1078-8956 (ISSN-L)
  • 1546-170X
DOI
10.1038/nm.3686
OpenAlex
W2069376956
Cited by
649
References
17
FWCI
19.82
Type
journal article
Language
en
Open access
green

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