Identification of complement C3a as a candidate biomarker in human chronic hepatitis C and HCV-related hepatocellular carcinoma using a proteomics approach.
Although the significant risk factors for hepatocellular carcinoma (HCC) are well known from epidemiological studies, diagnosis of this disease at an early stage is difficult, and HCC remains one of the leading causes of cancer death worldwide. Thus, to identify any useful HCC-related biomarkers is still a need. We performed SELDI-TOF MS to identify differentially expressed proteins in HCC serum using weak cation exchange protein chips. Protein characterization was performed by 2-DE separation and nano flow LC-MS/MS. A total of 55 sera were collected from HCC patients and compared with those from 48 patients with chronic hepatitis and 9 healthy individuals. A candidate marker of about 8900 Da was detected as differentially expressed in patients with chronic hepatitis C and hepatitis C virus (HCV)-related HCC. We identified this differentially expressed protein as complement C3a. The expression of C3a in HCC sera was further validated by PS20 chip immunoassay and Western blotting. Complement C3a was found to be elevated in patients with chronic hepatitis C and HCV-related HCC. The combination of SELDI-TOF MS and 2-DE provides a solution to identify disease-associated serum biomarkers.
Graduate Institute of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University, Taipei, Taiwan.
I-Neng
IN
Lee
Chien-Hung
CH
Chen
Jin-Chuan
JC
Sheu
Hsuan-Shu
HS
Lee
Guan-Tarn
GT
Huang
Ding-Shinn
DS
Chen
Chen-Yin
CY
Yu
Chu-Ling
CL
Wen
Fung-Jou
FJ
Lu
Lu-Ping
LP
Chow
D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood*; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000097:blood* / Q000175:diagnosis; D015926:Complement C3a / Q000032:analysis* / Q000378:metabolism; D015180:Electrophoresis, Gel, Two-Dimensional; D019698:Hepatitis C, Chronic / Q000097:blood* / Q000175:diagnosis; D006801:Humans; D008875:Middle Aged; D040081:Protein Array Analysis; D040901:Proteomics; D012016:Reference Values; D015203:Reproducibility of Results; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D014408:Biomarkers, Tumor; D015926:Complement C3a