Large scale identification of human hepatocellular carcinoma-associated antigens by autoantibodies.
Autoantibodies are often detected in hepatocellular carcinoma (HCC), and these responses may represent recognition of tumor Ags that are associated with transformation events. The identities of these Ags, however, are less well known. Using serological analysis of recombinant cDNA expression libraries (SEREX) from four HCC patients, we identified 55 independent cDNA sequences potentially encoding HCC tumor Ags. Of these genes, 15 are novel. Two such proteins, HCA587 and HCA661, were predominantly detected in testis, but not in other normal tissues, except for a weak expression in normal pancreas. In addition to HCC, these two Ags can be found in cancers of other histological types. Therefore, they can be categorized as cancer-testis (CT) Ags. Two other Ags (HCA519 and HCA90) were highly overexpressed in HCC and also expressed in cancer cell lines of lung, prostate, and pancreas, but not in the respective normal tissues. Four other Ags were identified to be expressed in particular types of cancer cell lines (HCA520 in an ovarian cancer cell line, HCA59 and HCA67 in a colon cancer cell line, HCA58 in colon and ovarian cancer cell lines), but not in the normal tissue counterpart(s). In addition, abundant expression of complement inactivation factors was found in HCC. These results indicate a broad range expression of autoantigens in HCC patients. Our findings open an avenue for the study of autoantigens in the transformation, metastasis, and immune evasion in HCC.
Wang
Yu
Y
Immunology Department, School of Basic Medical Science, Peking University Health Science Center, Beijing, China.
Han
Ke-Jun
KJ
Pang
Xue-Wen
XW
Vaughan
Hilary A
HA
Qu
Wei
W
Dong
Xue-Yuan
XY
Peng
Ji-Run
JR
Zhao
Hai-Tao
HT
Rui
Jing-An
JA
Leng
Xi-Sheng
XS
Cebon
Jonathan
J
Burgess
Antony W
AW
Chen
Wei-Feng
WF
D000368:Aged; D000912:Antibodies, Neoplasm / Q000032:analysis*; D000937:Antigen-Antibody Reactions / Q000235:genetics; D015295:Antigens, Tumor-Associated, Carbohydrate / Q000032:analysis* / Q000235:genetics / Q000276:immunology; D001323:Autoantibodies / Q000032:analysis*; D015152:Blotting, Northern; D006528:Carcinoma, Hepatocellular / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D018797:Cell Cycle Proteins; D018076:DNA, Complementary / Q000096:biosynthesis; D026261:Diazepam Binding Inhibitor / Q000032:analysis / Q000276:immunology; D015723:Gene Library; D006801:Humans; D007519:Isoantigens / Q000032:analysis / Q000235:genetics / Q000276:immunology; D008113:Liver Neoplasms / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D008875:Middle Aged; D008969:Molecular Sequence Data; D016254:Mutagenesis, Insertional / Q000276:immunology; D009928:Organ Specificity / Q000235:genetics / Q000276:immunology; D017384:Sequence Deletion / Q000276:immunology; D050680:Transcription Factor DP1; D014157:Transcription Factors / Q000032:analysis / Q000235:genetics / Q000276:immunology; D014407:Tumor Cells, Cultured
D000912:Antibodies, Neoplasm; D015295:Antigens, Tumor-Associated, Carbohydrate; D001323:Autoantibodies; D018797:Cell Cycle Proteins; D018076:DNA, Complementary; D026261:Diazepam Binding Inhibitor; D007519:Isoantigens; D050680:Transcription Factor DP1; D014157:Transcription Factors