A mouse to human search for plasma Proteome changes associated with pancreatic tumor development

被引：203

作者：

Faca, Vitor M. ^{[1
]}

Song, Kenneth S. ^{[1
]}

Wang, Hong ^{[1
]}

Zhang, Qing ^{[1
]}

Krasnoselsky, Alexei L. ^{[1
]}

Newcomb, Lisa F. ^{[1
]}

Plentz, Ruben R. ^{[2
]}

Gurumurthy, Sushma ^{[2
]}

Redston, Mark S. ^{[3
]}

Pitteri, Sharon J. ^{[1
]}

Pereira-Faca, Sandra R. ^{[1
]}

Ireton, Renee C. ^{[1
]}

Katayama, Hiroyuki ^{[1
]}

Glukhova, Veronika ^{[1
]}

Phanstiel, Douglas ^{[1
]}

Brenner, Dean E. ^{[4
]}

Anderson, Michelle A. ^{[4
]}

Misek, David ^{[4
]}

Scholler, Nathalie ^{[1
]}

Urban, Nicole D. ^{[1
]}

Barnett, Matt J. ^{[1
]}

Edelstein, Cim ^{[1
]}

Goodman, Gary E. ^{[1
]}

Thornquist, Mark D. ^{[1
]}

McIntosh, Martin W. ^{[1
]}

DePinho, Ronald A. ^{[5
,6
,7
]}

Bardeesy, Nabeel

Hanash, Samir M. ^{[1
]}

机构：

[1] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA

[2] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02115 USA

[3] Harvard Univ, Brigham & Womens Hosp, Boston, MA 02115 USA

[4] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA

[5] Harvard Univ, Sch Med, Ctr Appl Canc Sci, Belfer Inst Innovat Canc Sci, Boston, MA 02115 USA

[6] Harvard Univ, Sch Med, Dept Med Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA

[7] Harvard Univ, Sch Med, Dept Med & Genet, Dana Farber Canc Inst, Boston, MA 02115 USA

来源：

PLOS MEDICINE | 2008年 / 5卷 / 06期

关键词：

D O I：

10.1371/journal.pmed.0050123

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Background The complexity and heterogeneity of the human plasma proteome have presented significant challenges in the identification of protein changes associated with tumor development. Refined genetically engineered mouse ( GEM) models of human cancer have been shown to faithfully recapitulate the molecular, biological, and clinical features of human disease. Here, we sought to exploit the merits of a well-characterized GEM model of pancreatic cancer to determine whether proteomics technologies allow identification of protein changes associated with tumor development and whether such changes are relevant to human pancreatic cancer. Methods and Findings Plasma was sampled from mice at early and advanced stages of tumor development and from matched controls. Using a proteomic approach based on extensive protein fractionation, we confidently identified 1,442 proteins that were distributed across seven orders of magnitude of abundance in plasma. Analysis of proteins chosen on the basis of increased levels in plasma from tumor-bearing mice and corroborating protein or RNA expression in tissue documented concordance in the blood from 30 newly diagnosed patients with pancreatic cancer relative to 30 control specimens. A panel of five proteins selected on the basis of their increased level at an early stage of tumor development in the mouse was tested in a blinded study in 26 humans from the CARET (Carotene and Retinol Efficacy Trial) cohort. The panel discriminated pancreatic cancer cases from matched controls in blood specimens obtained between 7 and 13 mo prior to the development of symptoms and clinical diagnosis of pancreatic cancer. Conclusions Our findings indicate that GEM models of cancer, in combination with in-depth proteomic analysis, provide a useful strategy to identify candidate markers applicable to human cancer with potential utility for early detection.

引用

页码：953 / 967

页数：15

共 70 条

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