title: Serum Proteome Analysis for Profiling Predictive Protein Markers Associated with the Severity of Skin Lesions Induced by Ionizing Radiation.
abstract: The finding of new diagnostic and prognostic markers of local radiation injury, and particularly of the cutaneous radiation syndrome, is crucial for its medical management, in the case of both accidental exposure and radiotherapy side effects. Especially, a fast high-throughput method is still needed for triage of people accidentally exposed to ionizing radiation. In this study, we investigated the impact of localized irradiation of the skin on the early alteration of the serum proteome of mice in an effort to discover markers associated with the exposure and severity of impending damage. Using two different large-scale quantitative proteomic approaches, 2D-DIGE-MS and SELDI-TOF-MS, we performed global analyses of serum proteins collected in the clinical latency phase (days 3 and 7) from non-irradiated and locally irradiated mice exposed to high doses of 20, 40 and 80 Gy which will develop respectively erythema, moist desquamation and necrosis. Unsupervised and supervised multivariate statistical analyses (principal component analysis, partial-least square discriminant analysis and Random Forest analysis) using 2D-DIGE quantitative protein data allowed us to discriminate early between non-irradiated and irradiated animals, and between uninjured/slightly injured animals and animals that will develop severe lesions. On the other hand, despite a high number of animal replicates, PLS-DA and Random Forest analyses of SELDI-TOF-MS data failed to reveal sets of MS peaks able to discriminate between the different groups of animals. Our results show that, unlike SELDI-TOF-MS, the 2D-DIGE approach remains a powerful and promising method for the discovery of sets of proteins that could be used for the development of clinical tests for triage and the prognosis of the severity of radiation-induced skin lesions. We propose a list of 15 proteins which constitutes a set of candidate proteins for triage and prognosis of skin lesion outcomes.
authors.affiliation: Institut de Radioprotection et de Sûreté Nucléaire (IRSN), PRP-HOM, SRBE, LRTE, 31 avenue de la Division Leclerc, Fontenay-aux-Roses 92260, France. thibault.chaze@gmail.com.
authors.forename: Thibault
authors.initials: T
authors.lastname: Chaze
authors.affiliation: Laboratoire d'Oncologie Moléculaire Humaine, Centre Oscar Lambret, 3 rue Frédéric Combemale, BP 307, Lille 59020, France. L-Hornez@o-lambret.fr.
authors.forename: Louis
authors.initials: L
authors.lastname: Hornez
authors.affiliation: PFEM, Composante Protéomique, UR370, INRA, Saint-Genès Champanelle 63322, France. christophe.chambon@clermont.inra.fr.
authors.forename: Christophe
authors.initials: C
authors.lastname: Chambon
authors.affiliation: Spectrométrie de Masse Biologique et Protéomique, CNRS USR3149, ESPCI, 10 rue Vauquelin, Paris 75005, France. iman.haddad@espci.fr.
authors.forename: Iman
authors.initials: I
authors.lastname: Haddad
authors.affiliation: Spectrométrie de Masse Biologique et Protéomique, CNRS USR3149, ESPCI, 10 rue Vauquelin, Paris 75005, France. joelle.vinh@espci.fr.
authors.forename: Joelle
authors.initials: J
authors.lastname: Vinh
authors.affiliation: Laboratoire d'Oncologie Moléculaire Humaine, Centre Oscar Lambret, 3 rue Frédéric Combemale, BP 307, Lille 59020, France. JP-Peyrat@o-lambret.fr.
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Peyrat
authors.affiliation: Institut de Radioprotection et de Sûreté Nucléaire (IRSN), PRP-HOM, SRBE, LRTE, 31 avenue de la Division Leclerc, Fontenay-aux-Roses 92260, France. marc.benderitter@irsn.fr.
authors.forename: Marc
authors.initials: M
authors.lastname: Benderitter
authors.affiliation: Institut de Radioprotection et de Sûreté Nucléaire (IRSN), PRP-HOM, SRBE, LRTE, 31 avenue de la Division Leclerc, Fontenay-aux-Roses 92260, France. olivier.guipaud@irsn.fr.
authors.forename: Olivier
authors.initials: O
authors.lastname: Guipaud
keywords: 2D-DIGE; SELDI-TOF; biomarkers; cutaneous radiation syndrome; ionizing radiation; mass spectrometry; proteomics; radiotherapy; serum proteome; skin