title: Biomarker Panel for Chronic Graft-Versus-Host Disease.
abstract: To identify diagnostic and prognostic markers of chronic graft-versus-host disease (cGVHD), the major cause of morbidity and mortality after allogeneic hematopoietic cell transplantation (HCT).
  
  
  
  Using a quantitative proteomics approach, we compared pooled plasma samples obtained at matched time points after HCT (median, 103 days) from 35 patients with cGVHD and 18 without cGVHD (data are available via ProteomeXchange with identifier PXD002762). Of 105 proteins showing at least a 1.25-fold difference in expression, 22 were selected on the basis of involvement in relevant pathways and enzyme-linked immunosorbent assay availability. Chemokine (C-X-C motif) ligand 9 (CXCL9) and suppression of tumorigenicity 2 (ST2) also were measured on the basis of previously determined associations with GVHD. Concentrations of the four lead biomarkers were measured at or after diagnosis in plasma from two independent verification cohorts (n = 391) to determine their association with cGVHD. Their prognostic ability when measured at approximately day +100 after HCT was evaluated in plasma of a second verification cohort (n = 172).
  
  
  
  Of 24 proteins measured in the first verification cohort, nine proteins were associated with cGVHD, and only four (ST2, CXCL9, matrix metalloproteinase 3, and osteopontin) were necessary to compose a four-biomarker panel with an area under the receiver operating characteristic curve (AUC) of 0.89 and significant correlation with cGVHD diagnosis, cGVHD severity, and nonrelapse mortality. In a second verification cohort, this panel distinguished patients with cGVHD (AUC, 0.75), and finally, the panel measured at day +100 could predict cGVHD occurring within the next 3 months with an AUC of 0.67 and 0.79 without and with known clinical risk factors, respectively.
  
  
  
  We conclude that the biomarker panel measured at diagnosis or day +100 after HCT may allow patient stratification according to risk of cGVHD.
authors.affiliation: Jeffrey Yu, Kushi Kushekhar, Mohammad Abu Zaid, and Sophie Paczesny, Indiana University School of Medicine, Indianapolis, IN; Barry E. Storer, Paul J. Martin, Mary E. Flowers, John A. Hansen, Stephanie J. Lee, Qing Zhang, Philip R. Gafken, and Yuko Ogata, Fred Hutchinson Cancer Research Center; Barry E. Storer, University of Washington School of Medicine, Seattle, WA; Mukta Arora, University of Minnesota, Minneapolis, MN; Corey Cutler, Dana-Farber Cancer Institute, Boston, MA; Madan Jagasia, Vanderbilt University, Nashville, TN; Joseph Pidala, H. Lee Moffitt Cancer Center, Tampa, FL; Betty K. Hamilton, Cleveland Clinic Foundation, Cleveland, OH; George L. Chen, Roswell Park Cancer Institute, Buffalo, NY; and Iskra Pusic, Washington University School of Medicine, St Louis, MO.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Yu
authors.affiliation: Jeffrey Yu, Kushi Kushekhar, Mohammad Abu Zaid, and Sophie Paczesny, Indiana University School of Medicine, Indianapolis, IN; Barry E. Storer, Paul J. Martin, Mary E. Flowers, John A. Hansen, Stephanie J. Lee, Qing Zhang, Philip R. Gafken, and Yuko Ogata, Fred Hutchinson Cancer Research Center; Barry E. Storer, University of Washington School of Medicine, Seattle, WA; Mukta Arora, University of Minnesota, Minneapolis, MN; Corey Cutler, Dana-Farber Cancer Institute, Boston, MA; Madan Jagasia, Vanderbilt University, Nashville, TN; Joseph Pidala, H. Lee Moffitt Cancer Center, Tampa, FL; Betty K. Hamilton, Cleveland Clinic Foundation, Cleveland, OH; George L. Chen, Roswell Park Cancer Institute, Buffalo, NY; and Iskra Pusic, Washington University School of Medicine, St Louis, MO.
authors.forename: Barry E
authors.initials: BE
authors.lastname: Storer
authors.affiliation: Jeffrey Yu, Kushi Kushekhar, Mohammad Abu Zaid, and Sophie Paczesny, Indiana University School of Medicine, Indianapolis, IN; Barry E. Storer, Paul J. Martin, Mary E. Flowers, John A. Hansen, Stephanie J. Lee, Qing Zhang, Philip R. Gafken, and Yuko Ogata, Fred Hutchinson Cancer Research Center; Barry E. Storer, University of Washington School of Medicine, Seattle, WA; Mukta Arora, University of Minnesota, Minneapolis, MN; Corey Cutler, Dana-Farber Cancer Institute, Boston, MA; Madan Jagasia, Vanderbilt University, Nashville, TN; Joseph Pidala, H. Lee Moffitt Cancer Center, Tampa, FL; Betty K. Hamilton, Cleveland Clinic Foundation, Cleveland, OH; George L. Chen, Roswell Park Cancer Institute, Buffalo, NY; and Iskra Pusic, Washington University School of Medicine, St Louis, MO.
authors.forename: Kushi
authors.initials: K
authors.lastname: Kushekhar
authors.affiliation: Jeffrey Yu, Kushi Kushekhar, Mohammad Abu Zaid, and Sophie Paczesny, Indiana University School of Medicine, Indianapolis, IN; Barry E. Storer, Paul J. Martin, Mary E. Flowers, John A. Hansen, Stephanie J. Lee, Qing Zhang, Philip R. Gafken, and Yuko Ogata, Fred Hutchinson Cancer Research Center; Barry E. Storer, University of Washington School of Medicine, Seattle, WA; Mukta Arora, University of Minnesota, Minneapolis, MN; Corey Cutler, Dana-Farber Cancer Institute, Boston, MA; Madan Jagasia, Vanderbilt University, Nashville, TN; Joseph Pidala, H. Lee Moffitt Cancer Center, Tampa, FL; Betty K. Hamilton, Cleveland Clinic Foundation, Cleveland, OH; George L. Chen, Roswell Park Cancer Institute, Buffalo, NY; and Iskra Pusic, Washington University School of Medicine, St Louis, MO.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Abu Zaid
authors.affiliation: Jeffrey Yu, Kushi Kushekhar, Mohammad Abu Zaid, and Sophie Paczesny, Indiana University School of Medicine, Indianapolis, IN; Barry E. Storer, Paul J. Martin, Mary E. Flowers, John A. Hansen, Stephanie J. Lee, Qing Zhang, Philip R. Gafken, and Yuko Ogata, Fred Hutchinson Cancer Research Center; Barry E. Storer, University of Washington School of Medicine, Seattle, WA; Mukta Arora, University of Minnesota, Minneapolis, MN; Corey Cutler, Dana-Farber Cancer Institute, Boston, MA; Madan Jagasia, Vanderbilt University, Nashville, TN; Joseph Pidala, H. Lee Moffitt Cancer Center, Tampa, FL; Betty K. Hamilton, Cleveland Clinic Foundation, Cleveland, OH; George L. Chen, Roswell Park Cancer Institute, Buffalo, NY; and Iskra Pusic, Washington University School of Medicine, St Louis, MO.
authors.forename: Qing
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Jeffrey Yu, Kushi Kushekhar, Mohammad Abu Zaid, and Sophie Paczesny, Indiana University School of Medicine, Indianapolis, IN; Barry E. Storer, Paul J. Martin, Mary E. Flowers, John A. Hansen, Stephanie J. Lee, Qing Zhang, Philip R. Gafken, and Yuko Ogata, Fred Hutchinson Cancer Research Center; Barry E. Storer, University of Washington School of Medicine, Seattle, WA; Mukta Arora, University of Minnesota, Minneapolis, MN; Corey Cutler, Dana-Farber Cancer Institute, Boston, MA; Madan Jagasia, Vanderbilt University, Nashville, TN; Joseph Pidala, H. Lee Moffitt Cancer Center, Tampa, FL; Betty K. Hamilton, Cleveland Clinic Foundation, Cleveland, OH; George L. Chen, Roswell Park Cancer Institute, Buffalo, NY; and Iskra Pusic, Washington University School of Medicine, St Louis, MO.
authors.forename: Philip R
authors.initials: PR
authors.lastname: Gafken
authors.affiliation: Jeffrey Yu, Kushi Kushekhar, Mohammad Abu Zaid, and Sophie Paczesny, Indiana University School of Medicine, Indianapolis, IN; Barry E. Storer, Paul J. Martin, Mary E. Flowers, John A. Hansen, Stephanie J. Lee, Qing Zhang, Philip R. Gafken, and Yuko Ogata, Fred Hutchinson Cancer Research Center; Barry E. Storer, University of Washington School of Medicine, Seattle, WA; Mukta Arora, University of Minnesota, Minneapolis, MN; Corey Cutler, Dana-Farber Cancer Institute, Boston, MA; Madan Jagasia, Vanderbilt University, Nashville, TN; Joseph Pidala, H. Lee Moffitt Cancer Center, Tampa, FL; Betty K. Hamilton, Cleveland Clinic Foundation, Cleveland, OH; George L. Chen, Roswell Park Cancer Institute, Buffalo, NY; and Iskra Pusic, Washington University School of Medicine, St Louis, MO.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Ogata
authors.affiliation: Jeffrey Yu, Kushi Kushekhar, Mohammad Abu Zaid, and Sophie Paczesny, Indiana University School of Medicine, Indianapolis, IN; Barry E. Storer, Paul J. Martin, Mary E. Flowers, John A. Hansen, Stephanie J. Lee, Qing Zhang, Philip R. Gafken, and Yuko Ogata, Fred Hutchinson Cancer Research Center; Barry E. Storer, University of Washington School of Medicine, Seattle, WA; Mukta Arora, University of Minnesota, Minneapolis, MN; Corey Cutler, Dana-Farber Cancer Institute, Boston, MA; Madan Jagasia, Vanderbilt University, Nashville, TN; Joseph Pidala, H. Lee Moffitt Cancer Center, Tampa, FL; Betty K. Hamilton, Cleveland Clinic Foundation, Cleveland, OH; George L. Chen, Roswell Park Cancer Institute, Buffalo, NY; and Iskra Pusic, Washington University School of Medicine, St Louis, MO.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Martin
authors.affiliation: Jeffrey Yu, Kushi Kushekhar, Mohammad Abu Zaid, and Sophie Paczesny, Indiana University School of Medicine, Indianapolis, IN; Barry E. Storer, Paul J. Martin, Mary E. Flowers, John A. Hansen, Stephanie J. Lee, Qing Zhang, Philip R. Gafken, and Yuko Ogata, Fred Hutchinson Cancer Research Center; Barry E. Storer, University of Washington School of Medicine, Seattle, WA; Mukta Arora, University of Minnesota, Minneapolis, MN; Corey Cutler, Dana-Farber Cancer Institute, Boston, MA; Madan Jagasia, Vanderbilt University, Nashville, TN; Joseph Pidala, H. Lee Moffitt Cancer Center, Tampa, FL; Betty K. Hamilton, Cleveland Clinic Foundation, Cleveland, OH; George L. Chen, Roswell Park Cancer Institute, Buffalo, NY; and Iskra Pusic, Washington University School of Medicine, St Louis, MO.
authors.forename: Mary E
authors.initials: ME
authors.lastname: Flowers
authors.affiliation: Jeffrey Yu, Kushi Kushekhar, Mohammad Abu Zaid, and Sophie Paczesny, Indiana University School of Medicine, Indianapolis, IN; Barry E. Storer, Paul J. Martin, Mary E. Flowers, John A. Hansen, Stephanie J. Lee, Qing Zhang, Philip R. Gafken, and Yuko Ogata, Fred Hutchinson Cancer Research Center; Barry E. Storer, University of Washington School of Medicine, Seattle, WA; Mukta Arora, University of Minnesota, Minneapolis, MN; Corey Cutler, Dana-Farber Cancer Institute, Boston, MA; Madan Jagasia, Vanderbilt University, Nashville, TN; Joseph Pidala, H. Lee Moffitt Cancer Center, Tampa, FL; Betty K. Hamilton, Cleveland Clinic Foundation, Cleveland, OH; George L. Chen, Roswell Park Cancer Institute, Buffalo, NY; and Iskra Pusic, Washington University School of Medicine, St Louis, MO.
authors.forename: John A
authors.initials: JA
authors.lastname: Hansen
authors.affiliation: Jeffrey Yu, Kushi Kushekhar, Mohammad Abu Zaid, and Sophie Paczesny, Indiana University School of Medicine, Indianapolis, IN; Barry E. Storer, Paul J. Martin, Mary E. Flowers, John A. Hansen, Stephanie J. Lee, Qing Zhang, Philip R. Gafken, and Yuko Ogata, Fred Hutchinson Cancer Research Center; Barry E. Storer, University of Washington School of Medicine, Seattle, WA; Mukta Arora, University of Minnesota, Minneapolis, MN; Corey Cutler, Dana-Farber Cancer Institute, Boston, MA; Madan Jagasia, Vanderbilt University, Nashville, TN; Joseph Pidala, H. Lee Moffitt Cancer Center, Tampa, FL; Betty K. Hamilton, Cleveland Clinic Foundation, Cleveland, OH; George L. Chen, Roswell Park Cancer Institute, Buffalo, NY; and Iskra Pusic, Washington University School of Medicine, St Louis, MO.
authors.forename: Mukta
authors.initials: M
authors.lastname: Arora
authors.affiliation: Jeffrey Yu, Kushi Kushekhar, Mohammad Abu Zaid, and Sophie Paczesny, Indiana University School of Medicine, Indianapolis, IN; Barry E. Storer, Paul J. Martin, Mary E. Flowers, John A. Hansen, Stephanie J. Lee, Qing Zhang, Philip R. Gafken, and Yuko Ogata, Fred Hutchinson Cancer Research Center; Barry E. Storer, University of Washington School of Medicine, Seattle, WA; Mukta Arora, University of Minnesota, Minneapolis, MN; Corey Cutler, Dana-Farber Cancer Institute, Boston, MA; Madan Jagasia, Vanderbilt University, Nashville, TN; Joseph Pidala, H. Lee Moffitt Cancer Center, Tampa, FL; Betty K. Hamilton, Cleveland Clinic Foundation, Cleveland, OH; George L. Chen, Roswell Park Cancer Institute, Buffalo, NY; and Iskra Pusic, Washington University School of Medicine, St Louis, MO.
authors.forename: Corey
authors.initials: C
authors.lastname: Cutler
authors.affiliation: Jeffrey Yu, Kushi Kushekhar, Mohammad Abu Zaid, and Sophie Paczesny, Indiana University School of Medicine, Indianapolis, IN; Barry E. Storer, Paul J. Martin, Mary E. Flowers, John A. Hansen, Stephanie J. Lee, Qing Zhang, Philip R. Gafken, and Yuko Ogata, Fred Hutchinson Cancer Research Center; Barry E. Storer, University of Washington School of Medicine, Seattle, WA; Mukta Arora, University of Minnesota, Minneapolis, MN; Corey Cutler, Dana-Farber Cancer Institute, Boston, MA; Madan Jagasia, Vanderbilt University, Nashville, TN; Joseph Pidala, H. Lee Moffitt Cancer Center, Tampa, FL; Betty K. Hamilton, Cleveland Clinic Foundation, Cleveland, OH; George L. Chen, Roswell Park Cancer Institute, Buffalo, NY; and Iskra Pusic, Washington University School of Medicine, St Louis, MO.
authors.forename: Madan
authors.initials: M
authors.lastname: Jagasia
authors.affiliation: Jeffrey Yu, Kushi Kushekhar, Mohammad Abu Zaid, and Sophie Paczesny, Indiana University School of Medicine, Indianapolis, IN; Barry E. Storer, Paul J. Martin, Mary E. Flowers, John A. Hansen, Stephanie J. Lee, Qing Zhang, Philip R. Gafken, and Yuko Ogata, Fred Hutchinson Cancer Research Center; Barry E. Storer, University of Washington School of Medicine, Seattle, WA; Mukta Arora, University of Minnesota, Minneapolis, MN; Corey Cutler, Dana-Farber Cancer Institute, Boston, MA; Madan Jagasia, Vanderbilt University, Nashville, TN; Joseph Pidala, H. Lee Moffitt Cancer Center, Tampa, FL; Betty K. Hamilton, Cleveland Clinic Foundation, Cleveland, OH; George L. Chen, Roswell Park Cancer Institute, Buffalo, NY; and Iskra Pusic, Washington University School of Medicine, St Louis, MO.
authors.forename: Joseph
authors.initials: J
authors.lastname: Pidala
authors.affiliation: Jeffrey Yu, Kushi Kushekhar, Mohammad Abu Zaid, and Sophie Paczesny, Indiana University School of Medicine, Indianapolis, IN; Barry E. Storer, Paul J. Martin, Mary E. Flowers, John A. Hansen, Stephanie J. Lee, Qing Zhang, Philip R. Gafken, and Yuko Ogata, Fred Hutchinson Cancer Research Center; Barry E. Storer, University of Washington School of Medicine, Seattle, WA; Mukta Arora, University of Minnesota, Minneapolis, MN; Corey Cutler, Dana-Farber Cancer Institute, Boston, MA; Madan Jagasia, Vanderbilt University, Nashville, TN; Joseph Pidala, H. Lee Moffitt Cancer Center, Tampa, FL; Betty K. Hamilton, Cleveland Clinic Foundation, Cleveland, OH; George L. Chen, Roswell Park Cancer Institute, Buffalo, NY; and Iskra Pusic, Washington University School of Medicine, St Louis, MO.
authors.forename: Betty K
authors.initials: BK
authors.lastname: Hamilton
authors.affiliation: Jeffrey Yu, Kushi Kushekhar, Mohammad Abu Zaid, and Sophie Paczesny, Indiana University School of Medicine, Indianapolis, IN; Barry E. Storer, Paul J. Martin, Mary E. Flowers, John A. Hansen, Stephanie J. Lee, Qing Zhang, Philip R. Gafken, and Yuko Ogata, Fred Hutchinson Cancer Research Center; Barry E. Storer, University of Washington School of Medicine, Seattle, WA; Mukta Arora, University of Minnesota, Minneapolis, MN; Corey Cutler, Dana-Farber Cancer Institute, Boston, MA; Madan Jagasia, Vanderbilt University, Nashville, TN; Joseph Pidala, H. Lee Moffitt Cancer Center, Tampa, FL; Betty K. Hamilton, Cleveland Clinic Foundation, Cleveland, OH; George L. Chen, Roswell Park Cancer Institute, Buffalo, NY; and Iskra Pusic, Washington University School of Medicine, St Louis, MO.
authors.forename: George L
authors.initials: GL
authors.lastname: Chen
authors.affiliation: Jeffrey Yu, Kushi Kushekhar, Mohammad Abu Zaid, and Sophie Paczesny, Indiana University School of Medicine, Indianapolis, IN; Barry E. Storer, Paul J. Martin, Mary E. Flowers, John A. Hansen, Stephanie J. Lee, Qing Zhang, Philip R. Gafken, and Yuko Ogata, Fred Hutchinson Cancer Research Center; Barry E. Storer, University of Washington School of Medicine, Seattle, WA; Mukta Arora, University of Minnesota, Minneapolis, MN; Corey Cutler, Dana-Farber Cancer Institute, Boston, MA; Madan Jagasia, Vanderbilt University, Nashville, TN; Joseph Pidala, H. Lee Moffitt Cancer Center, Tampa, FL; Betty K. Hamilton, Cleveland Clinic Foundation, Cleveland, OH; George L. Chen, Roswell Park Cancer Institute, Buffalo, NY; and Iskra Pusic, Washington University School of Medicine, St Louis, MO.
authors.forename: Iskra
authors.initials: I
authors.lastname: Pusic
authors.affiliation: Jeffrey Yu, Kushi Kushekhar, Mohammad Abu Zaid, and Sophie Paczesny, Indiana University School of Medicine, Indianapolis, IN; Barry E. Storer, Paul J. Martin, Mary E. Flowers, John A. Hansen, Stephanie J. Lee, Qing Zhang, Philip R. Gafken, and Yuko Ogata, Fred Hutchinson Cancer Research Center; Barry E. Storer, University of Washington School of Medicine, Seattle, WA; Mukta Arora, University of Minnesota, Minneapolis, MN; Corey Cutler, Dana-Farber Cancer Institute, Boston, MA; Madan Jagasia, Vanderbilt University, Nashville, TN; Joseph Pidala, H. Lee Moffitt Cancer Center, Tampa, FL; Betty K. Hamilton, Cleveland Clinic Foundation, Cleveland, OH; George L. Chen, Roswell Park Cancer Institute, Buffalo, NY; and Iskra Pusic, Washington University School of Medicine, St Louis, MO.
authors.forename: Stephanie J
authors.initials: SJ
authors.lastname: Lee
authors.affiliation: Jeffrey Yu, Kushi Kushekhar, Mohammad Abu Zaid, and Sophie Paczesny, Indiana University School of Medicine, Indianapolis, IN; Barry E. Storer, Paul J. Martin, Mary E. Flowers, John A. Hansen, Stephanie J. Lee, Qing Zhang, Philip R. Gafken, and Yuko Ogata, Fred Hutchinson Cancer Research Center; Barry E. Storer, University of Washington School of Medicine, Seattle, WA; Mukta Arora, University of Minnesota, Minneapolis, MN; Corey Cutler, Dana-Farber Cancer Institute, Boston, MA; Madan Jagasia, Vanderbilt University, Nashville, TN; Joseph Pidala, H. Lee Moffitt Cancer Center, Tampa, FL; Betty K. Hamilton, Cleveland Clinic Foundation, Cleveland, OH; George L. Chen, Roswell Park Cancer Institute, Buffalo, NY; and Iskra Pusic, Washington University School of Medicine, St Louis, MO. sophpacz@iu.edu.
authors.forename: Sophie
authors.initials: S
authors.lastname: Paczesny
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood*; D054370:Chemokine CXCL9 / Q000097:blood; D002908:Chronic Disease; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006086:Graft vs Host Disease / Q000175:diagnosis*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D000072179:Interleukin-1 Receptor-Like 1 Protein / Q000097:blood; D008297:Male; D019278:Matrix Metalloproteinase 3 / Q000097:blood; D008875:Middle Aged; D053495:Osteopontin / Q000097:blood; D011183:Postoperative Complications; D011379:Prognosis; D011446:Prospective Studies; D013997:Time Factors
chemical_list: D015415:Biomarkers; D054370:Chemokine CXCL9; C079241:IL1RL1 protein, human; D000072179:Interleukin-1 Receptor-Like 1 Protein; D053495:Osteopontin; D019278:Matrix Metalloproteinase 3