Identification of two novel CT antigens and their capacity to elicit antibody response in hepatocellular carcinoma patients

• Published in: British journal of cancer Vol. 89; no. 2; pp. 291 - 297
• Main Authors: DONG, X-Y, SU, Y-R, QIAN, X-P, YANG, X-A, PANG, X-W, WU, H-Y, CHEN, W-F
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing Group 21.07.2003
• Subjects: Amino acids; Antibodies; Antibody Formation; Antigens; Antigens, Neoplasm - immunology; Biological and medical sciences; Blotting, Western; Cancer research; Carcinoma, Hepatocellular - immunology; Carcinoma, Hepatocellular - pathology; Colorectal cancer; Databases, Factual; DNA-Binding Proteins - analysis; DNA-Binding Proteins - biosynthesis; Enzyme-Linked Immunosorbent Assay; Gastroenterology. Liver. Pancreas. Abdomen; Gene Expression Regulation, Neoplastic; Genes; Humans; Immunotherapy; Liver cancer; Liver Neoplasms - immunology; Liver Neoplasms - pathology; Liver. Biliary tract. Portal circulation. Exocrine pancreas; Lung cancer; Medical research; Medical sciences; Membrane Proteins - analysis; Membrane Proteins - biosynthesis; Molecular and Cellular Pathology; Phosphoric Monoester Hydrolases; Protein Tyrosine Phosphatases - analysis; Protein Tyrosine Phosphatases - biosynthesis; Proteins; PTEN Phosphohydrolase; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - biosynthesis; Transcription Factors - analysis; Transcription Factors - biosynthesis; Tumors; Vaccines; Human; Immune response; Cancer testis antigen; antibody response; Tumor associated antigen; CT antigen; Digestive diseases; Hepatic disease; Hepatocellular carcinoma; Tumoral marker; Malignant tumor; Humoral immunity
• DOI: 10.1038/sj.bjc.6601062
• ISSN: 0007-0920

FATE and TPTE genes were originally reported to be specifically expressed in the adult testis. We searched for the databases of Unigene and serial analysis of gene expression (SAGE) implying that these two gene transcripts might also be expressed in tumours. Herein, we demonstrated that FATE and TPTE mRNA transcripts were expressed in different histological types of tumours and normal testis. Both are cancer-testis (CT) antigens and renamed as FATE/BJ-HCC-2 and TPTE/BJ-HCC-5, respectively. Comparison at nucleotide sequence, the FATE/BJ-HCC-2 cDNA, was identical to that of FATE, whereas the TPTE/BJ-HCC-5 was found to have two isoforms in both cancers and testis: one was identical in cDNA sequence to TPTE, encoding a protein of 551 amino acids, and the other variant lacked an exon of 54 bp, encoding a protein of 533 amino acids. The mRNA expression was analysed by RT-PCR and real-time PCR. FATE/BJ-HCC-2 mRNA was detected in 66% (41 out of 62) in hepatocellular carcinoma (HCC) samples and 21% (three out of 14) in colon cancer samples, whereas the TPTE/BJ-HCC-5 mRNA was detected in 39% (24 out of 62) and 36% (five out of 14) in HCC and non-small lung cancer samples, respectively. The recombinant proteins were prepared and the reactivity of allogenic sera to these two antigens was screened. The frequency of antibody response against FATE/BJ-HCC-2 and TPTE/BJ-HCC-5 proteins was 7.3% (three out of 41) and 25.0% (six out of 24), respectively, in HCC patients bearing respective gene transcripts. Therefore, FATE/BJ-HCC-2 and TPTE/BJ-HCC-5 are the novel CT antigens capable of eliciting antibody response in cancer patients.