A quantitative proteomic approach for identification of potential biomarkers in hepatocellular carcinoma.
Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide. In this study, our objective was to identify differentially regulated proteins in HCC through a quantitative proteomic approach using iTRAQ. More than 600 proteins were quantitated of which 59 proteins were overexpressed and 92 proteins were underexpressed in HCC as compared to adjacent normal tissue. Several differentially expressed proteins were not implicated previously in HCC. A subset of these proteins (six each from upregulated and downregulated groups) was further validated using immunoblotting and immunohistochemical labeling. Some of the overexpressed proteins with no previous description in the context of HCC include fibroleukin, interferon induced 56 kDa protein, milk fat globule-EGF factor 8, and myeloid-associated differentiation marker. Interestingly, all the enzymes of urea metabolic pathway were dramatically downregulated. Immunohistochemical labeling confirmed differential expression of fibroleukin, myeloid associated differentiation marker and ornithine carbamoyl transferase in majority of HCC samples analyzed. Our results demonstrate quantitative proteomics as a robust discovery tool for the identification of differentially regulated proteins in cancers.
Chaerkady
Raghothama
R
Institute of Bioinformatics, International Technology Park, Bangalore 560066, India.
Harsha
H C
HC
Nalli
Anuradha
A
Gucek
Marjan
M
Vivekanandan
Perumal
P
Akhtar
Javed
J
Cole
Robert N
RN
Simmers
Jessica
J
Schulick
Richard D
RD
Singh
Sujay
S
Torbenson
Michael
M
Pandey
Akhilesh
A
Thuluvath
Paul J
PJ
D000595:Amino Acid Sequence; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000235:genetics; D006528:Carcinoma, Hepatocellular / Q000737:chemistry*; D006801:Humans; D008099:Liver / Q000737:chemistry* / Q000473:pathology; D008113:Liver Neoplasms / Q000737:chemistry*; D015335:Molecular Probes / Q000378:metabolism; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000032:analysis* / Q000235:genetics; D020543:Proteome / Q000032:analysis*; D040901:Proteomics / Q000379:methods*; D015203:Reproducibility of Results; D046888:Tissue Array Analysis
D014408:Biomarkers, Tumor; D015335:Molecular Probes; D009363:Neoplasm Proteins; D020543:Proteome