title: Differences in the whole saliva baseline proteome profile associated with development of oral mucositis in head and neck cancer patients undergoing radiotherapy.
abstract: Oral mucositis (OM) is a common, painful and often treatment-limiting side effect of radiotherapy (RT) for head and neck cancer (HNC) patients. Unstimulated saliva was collected before the first radiotherapy application in 50 HNC patients. 41 out of 50 patients developed OM (grade III) during radiotherapy, of which 14 patients even displayed an early OM (grade III) at a low radiation dose of 30Gy. Nine patients did not develop OM (grade III). Using an LC-MS/MS approach 5323 tryptic peptides were assigned to 487 distinct proteins (≥2 peptides) in the data set. The levels of 48 proteins differed significantly (p<0.05) between patients developing OM or not. 17 proteins displayed increased levels (≥1.3-fold) and 31 proteins decreased in level in OM, respectively. Furthermore, using partial least square analysis protein patterns could be used to distinguish subjects which did not develop grade III OM even after 70Gy total dose (n=9) and those displaying early OM (grade III at <30Gy total dose, n=14). Using leave one out cross validation 37 of 41 patients (90%) developing OM could be correctly assigned indicating that prognostic proteome signatures may help identify patients that should be specifically monitored to increase overall effectiveness of RT treatment.
authors.affiliation: Department of Functional Genomics, Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, Germany.
authors.forename: Nico
authors.initials: N
authors.lastname: Jehmlich
authors.affiliation: Department of Radiation Oncology, University Medical Center Freiburg, Germany.
authors.forename: Petra
authors.initials: P
authors.lastname: Stegmaier
authors.affiliation: Department of Functional Genomics, Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, Germany.
authors.forename: Claas
authors.initials: C
authors.lastname: Golatowski
authors.affiliation: Department of Functional Genomics, Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, Germany.
authors.forename: Manuela Gesell
authors.initials: MG
authors.lastname: Salazar
authors.affiliation: Department of Radiation Oncology, University Medical Center Freiburg, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Rischke
authors.affiliation: Department of Radiation Oncology, University Medical Center Freiburg, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Henke
authors.affiliation: Department of Functional Genomics, Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, Germany. Electronic address: voelker@uni-greifswald.de.
authors.forename: Uwe
authors.initials: U
authors.lastname: Völker
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D006258:Head and Neck Neoplasms / Q000378:metabolism / Q000532:radiotherapy; D006801:Humans; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism*; D011446:Prospective Studies; D020543:Proteome / Q000378:metabolism*; D012463:Saliva / Q000378:metabolism*; D012471:Salivary Proteins and Peptides / Q000378:metabolism*; D013280:Stomatitis / Q000378:metabolism / Q000532:radiotherapy
chemical_list: D009363:Neoplasm Proteins; D020543:Proteome; D012471:Salivary Proteins and Peptides
keywords: Head and neck cancer; Oral mucositis; Prospective study; Radiochemotherapy; Radiotherapy; Whole saliva