title: SELDI-TOF MS profiling of serum for detection of the progression of chronic hepatitis C to hepatocellular carcinoma.
abstract: Proteomic profiling of serum is an emerging technique to identify new biomarkers indicative of disease severity and progression. The objective of our study was to assess the use of surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS) to identify multiple serum protein biomarkers for detection of liver disease progression to hepatocellular carcinoma (HCC). A cohort of 170 serum samples obtained from subjects in the United States with no liver disease (n = 39), liver diseases not associated with cirrhosis (n = 36), cirrhosis (n = 38), or HCC (n = 57) were applied to metal affinity protein chips for protein profiling by SELDI-TOF MS. Across the four test groups, 38 differentially expressed proteins were used to generate multiple decision classification trees to distinguish the known disease states. Analysis of a subset of samples with only hepatitis C virus (HCV)-related disease was emphasized. The serum protein profiles of control patients were readily distinguished from each HCV-associated disease state. Two-way comparisons of chronic hepatitis C, HCV cirrhosis, or HCV-HCC versus healthy had a sensitivity/specificity range of 74% to 95%. For distinguishing chronic HCV from HCV-HCC, a sensitivity of 61% and a specificity of 76% were obtained. However, when the values of known serum markers alpha fetoprotein, des-gamma carboxyprothrombin, and GP73 were combined with the SELDI peak values, the sensitivity and specifity improved to 75% and 92%, respectively. In conclusion, SELDI-TOF MS serum profiling is able to distinguish HCC from liver disease before cirrhosis as well as cirrhosis, especially in patients with HCV infection compared with other etiologies.
authors.affiliation: Department of Microbiology and Molecular Cell Biology, Eastern Virginia Medical School, Norfolk, VA, USA.
authors.forename: E Ellen
authors.initials: EE
authors.lastname: Schwegler
authors.forename: Lisa
authors.initials: L
authors.lastname: Cazares
authors.forename: Laura F
authors.initials: LF
authors.lastname: Steel
authors.forename: Bao-Ling
authors.initials: BL
authors.lastname: Adam
authors.forename: David A
authors.initials: DA
authors.lastname: Johnson
authors.forename: O John
authors.initials: OJ
authors.lastname: Semmes
authors.forename: Timothy M
authors.initials: TM
authors.lastname: Block
authors.forename: Jorge A
authors.initials: JA
authors.lastname: Marrero
authors.forename: Richard R
authors.initials: RR
authors.lastname: Drake
mesh_terms: D000328:Adult; D000368:Aged; D001798:Blood Proteins / Q000032:analysis*; D006528:Carcinoma, Hepatocellular / Q000209:etiology*; D003663:Decision Trees; D018450:Disease Progression; D005260:Female; D019698:Hepatitis C, Chronic / Q000097:blood* / Q000150:complications; D006801:Humans; D008113:Liver Neoplasms / Q000209:etiology*; D008297:Male; D008875:Middle Aged; D040901:Proteomics; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D001798:Blood Proteins