title: Proteomic analysis of oral cavity squamous cell carcinoma specimens identifies patient outcome-associated proteins.
abstract: BACKGROUND
  Global proteomic analysis of oral cavity squamous cell carcinoma was performed to identify changes that reflect patient outcomes.
  
  
  OBJECTIVE
  To identify differentially expressed proteins associated with patient outcomes and to explore the use of imaging mass spectrometry as a clinical tool to identify clinically relevant proteins.
  
  
  METHODS
  Two-dimensional separation of digested peptides generated from 43 specimens with high-resolution mass spectrometry identified proteins associated with disease-specific death, distant metastasis, and loco-regional recurrence. RNA expressions had been correlated to protein levels to test transcriptional regulation of clinically relevant proteins. Imaging mass spectrometry explored an alternative platform for assessing clinically relevant proteins that would complement surgical pathologic diagnosis.
  
  
  RESULTS
  Seventy-two peptide features were found to be associated with 3 patient outcomes: disease-specific death (9), distant metastasis (16), and loco-regional recurrence (39); 8 of them were associated with multiple outcomes. Functional ontology revealed major changes in cell adhesion and calcium binding. Thirteen RNAs showed strong correlation with their encoded proteins, implying transcriptional control. Reduction of DSP, PKP1, and TRIM29 was associated with significantly shorter time to onset of distant metastasis. Reduction of PKP1 and TRIM29 correlated with poorer disease-specific survival. Additionally, S100A8 and S100A9 reductions were verified for their association with poor prognosis using imaging mass spectrometry, a platform more adaptable for use with surgical pathology.
  
  
  CONCLUSIONS
  Using global proteomic analysis, we have identified proteins associated with clinical outcomes. The list of clinically relevant proteins observed will provide a means to develop clinical assays for prognosis and optimizing treatment selection.
authors.affiliation: From the Departments of Pathology (Drs Harris, Belbin, Wang, Ow, Childs, Prystowsky, and Lim and Ms Kawachi), Epidemiology & Population Health (Dr Schlecht), Developmental and Molecular Biology (Dr Angeletti), and Biochemistry (Dr Angeletti) and the Laboratory for Macromolecular Analysis & Proteomics (Drs Angeletti and Lim), Albert Einstein College of Medicine, Bronx, New York; High Performance and Research Computing, Department of Information Systems and Technology, UMDNJ, Newark, New Jersey (Dr Du); the Department of Otorhinolaryngology-Head & Neck Surgery, Montefiore Medical Center, Bronx, New York (Drs Ow and Smith); and the Department of Pathology, Henry Ford Hospital and Medical Group, Detroit, Michigan (Dr Keller).
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Harris
authors.forename: Peicheng
authors.initials: P
authors.lastname: Du
authors.forename: Nicole
authors.initials: N
authors.lastname: Kawachi
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Belbin
authors.forename: Yanhua
authors.initials: Y
authors.lastname: Wang
authors.forename: Nicolas F
authors.initials: NF
authors.lastname: Schlecht
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Ow
authors.forename: Christian E
authors.initials: CE
authors.lastname: Keller
authors.forename: Geoffrey J
authors.initials: GJ
authors.lastname: Childs
authors.forename: Richard V
authors.initials: RV
authors.lastname: Smith
authors.forename: Ruth Hogue
authors.initials: RH
authors.lastname: Angeletti
authors.forename: Michael B
authors.initials: MB
authors.lastname: Prystowsky
authors.forename: Jihyeon
authors.initials: J
authors.lastname: Lim
mesh_terms: D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism*; D002853:Chromatography, Liquid; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000235:genetics / Q000378:metabolism*; D010455:Peptides / Q000737:chemistry / Q000378:metabolism; D011379:Prognosis; D020543:Proteome / Q000235:genetics / Q000378:metabolism*; D040901:Proteomics / Q000379:methods*; D020539:Sequence Analysis, Protein; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D053719:Tandem Mass Spectrometry
chemical_list: D010455:Peptides; D020543:Proteome