Identification of autoantibody against fatty acid synthase in hepatocellular carcinoma mouse model and its application to diagnosis of HCC.
Autoantibodies, which are generated by immune system recognizing the presence of the abnormal tumor-associated antigens, are promising biomarkers for early detection of tumors. Recently, we established a B cell hybridoma pool derived from H-ras12V transgenic mouse, a typical hepatocellular carcinoma model, as a source of tumor-associated autoantibodies without using any extracellular antigens and have characterized the specific target antigens against them. K1 autoantibody, one of them, was investigated in this study and its target antigen was identified by mass spectrometric analysis as fatty acid synthase (FASN), an important oncogenic protein. Moreover, a specific mimotope against K1 autoantibody was screened from the cyclic random hepta-peptide phage library and, using it as a coating antigen for ELISA, we could distinguish patients with hepatocellular carcinoma (HCC) vs. normal subjects with 96.55% sensitivity and 100% specificity. These results imply that anti-FASN autoantibody is induced in patients with HCC and detection of anti-FASN autoantibody can be used for the diagnosis of HCC.
Heo
Chang-Kyu
CK
Daejeon-KRIBB-FHCRC Research Cooperation Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Yuseong-gu, Daejeon 305-860, Korea.
Woo
Mi-Kyung
MK
Yu
Dae-Yeul
DY
Lee
Ju Yeon
JY
Yoo
Jong Shin
JS
Yoo
Hyang Sook
HS
Ko
Jeong Heon
JH
Kim
Jin-Man
JM
Choi
Jong Young
JY
Kim
In Gyu
IG
Paik
Sang Gi
SG
Cho
Eun-Wie
EW
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D001323:Autoantibodies / Q000276:immunology; D001324:Autoantigens / Q000276:immunology; D014408:Biomarkers, Tumor / Q000276:immunology; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000097:blood / Q000175:diagnosis* / Q000276:immunology; D002469:Cell Separation; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods*; D064429:Fatty Acid Synthases / Q000276:immunology*; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D047468:Immunoprecipitation; D008113:Liver Neoplasms / Q000097:blood / Q000175:diagnosis* / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012680:Sensitivity and Specificity
D000911:Antibodies, Monoclonal; D001323:Autoantibodies; D001324:Autoantigens; D014408:Biomarkers, Tumor; D064429:Fatty Acid Synthases; C495971:Hras protein, mouse; D016283:Proto-Oncogene Proteins p21(ras)