Summary
Many studies demonstrated that cancer sera contain antibodies which react with autologous cellular antigens generally known as tumor-associated antigens (TAAs). In our laboratories, the approach used in the identification of TAAs has involved initially examining the sera of cancer patients using extracts of tissue culture cells as source of antigens in Western blotting and by indirect immunofluorescence on whole cells. With these two techniques, we identify sera which have high-titer fluorescent staining or strong signals to cell extracts on Western blotting and subsequently use these sera as probes in immunoscreening cDNA expression libraries, and also in proteomic approaches to isolate and identify targeted antigens which might potentially be involved in malignant transformation. In this manner, several novel TAAs including HCC1, p62, p90, and others have been identified. In extension of these studies, we evaluate the sensitivity and specificity of different antigen-antibody systems as markers in cancer in order to develop “tumor-associated antigen array” systems for cancer diagnosis, cancer prediction, and for following the response of patients to treatment.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Tan, E.M. (2001) Autoantibodies as reporters identifying aberrant cellular mechanisms in tumorigenesis. J Clin Invest 108, 1411–1415
Old, L.J. and Chen, Y.T. (1998) New paths in human cancer serology. J Exp Med 187, 1163–1167
Zhang, J.Y., Casiano, C.A., Peng, X. X., Koziol, J. A., Chan, E. K. L., and Tan, E. M. (2003) Enhancement of antibody detection in cancer using panel of recombinant tumor-associated antigens. Cancer Epidemiol Biomarkers Prev 12:136–143
Crawford, L. V., Pim, D. C. and Bulbrook, R. D. (1982) Detection of antibodies against the cellular protein p53 in sera from patients with breast cancer. Int J Cancer 30, 403–408
Soussi, T. (2000) p53 antibodies in the sera of patients with various types of cancer. A review. Cancer Res 60, 1777–1788
Disis, M.L., Pupa, S.M., Gralow, J.R., Dittadi, R., Menard, S., Cheever, M.A. (1997) High-titer HER-2/neu protein-specific antibody can be detected in patients with early-stage breast cancer. J Clin Oncol 15, 3363–7
Zhang, J. Y., Chan, E. K. L., Peng, X. X., and Tan, E. M. (1999) A novel cytoplasmic protein with RNA-binding motifs is an autoantigen in human hepatocellular carcinoma. J Exp Med 189, 1101–1110
Doyle, G.A., Bourdeaux-Heller, J.M., Coulthard, S., Meisner, L.F. and Ross, J. (2000) Amplification in human breast cancer of a gene encoding a c-myc mRNA binding protein. Cancer Res 60, 2756–2759
Keene, J. D. (1999) Why is Hu where? Shuttling of early response gene messenger RNA subsets. Proc Natl Acad Sci USA 96, 5–7
Stockert, E., Jager, E., Chen, Y.T., Scanlan, M.J., Gout, I., Karbach, J., Arand, M.,Knuth, A., and Old, L.J. (1998) A survey of humoral immune response of cancer patients to a panel of human tumor antigens. J Exp Med 187, 1349–1354
Ambrosini, G., Adida, C. and Altieri, D.C. (1997) A novel anti-apoptosis gene, survivin, expressed in cancer and lymphoma. Nat Med 3, 917–992
Daniels, T., Zhang, J., Gutierrez, I., Elliot, M. L., Yamada B, Heeb MJ, Sheets SM, Wu X, and Casiano CA.(2005) Antinuclear autoantibodies in PCa: Immunity to LEDGF/p75, a survival protein highly expressed in prostate tumors and cleaved during apoptosis. Prostate 62, 14–26
Winter, S.F., Minna, J.D., Johnson, B.E., Takahashi, T., Gazdar, A.F., and Carbone, D.P. (1992) Development of antibodies against p53 in lung cancer patients appears to be dependent on the type of p53 mutation. Cancer Res 52, 4168–4174
Lu, M., Nakamura, R.M., Dent, E.D., Zhang, J.Y., Nielsen, F.C., Christiansen, J.,Chan, E.K., and Tan, E.M. (2001) Aberrant expression of fetal RNA-binding protein p62 in liver cancer and liver cirrhosis. Am J Pathol 159, 945–953
Imai, H., Nakano, Y., Kiyosawa, K., and Tan, E.M. (1993) Increasing titers and changing specificities of antinuclear antibodies in patients with chronic liver disease who develop hepatocellular carcinoma. Cancer 71, 26–35
Anderson, K. S., and LaBaer, J. (2005) The sentinel within: exploiting the immune system for cancer biomarkers. J Proteome Res 4, 1123–1133
Disis, M.L., Montgomery, R.B., Goodell, V., dela Rosa, C., and Salazar, L.G. (2005) Antibody immunity to cancer-associated proteins. The Education Book of the 96th Annual AACR Meeting, Anaheim, CA, p166–169
Imai H, Chan EKL, Kiyosawa K, Fu XD, Tan EM. (1993) Novel nuclear antoantigen with splicing factor motifs identified with antibody from hepatocellular carcinoma. J Clin Invest 92, 2419–2426
Landberg G, Tan EM. (1994) Characterization of a DNA-binding nuclear autoantigen mainly associated with S phase and G2 cells. Exp Cell Res 212, 255–261
Casiano CA, Landberg G, Ochs R, Tan EM. (1993) Autoantibodies to a novel cell cycle-regulated protein that accumulates in the nuclear matrix during S phase and is localized in the kinetochores and spindle midzone during mitosis. J Cell Sci 106, 1045–1056
Soo Hoo L, Zhang JY, Chan EKL. (2002) Cloning and characterization of a novel 90kDa ‘companion’ auto-antigen of p62 overexpressed in cancer. Oncogene 21, 5006–5015
Sahin U, Tureci O, Schmitt H, Cochlovius B, Johannes T, Schmits R, Stenner F, Luo G, Schobert I, Pfreundschuh M. (1995) Human neoplasms elicit multiple specific immune responses in the autologous host. Proc Natl Acad Sci USA 92, 11810–11813
Chambers JC, Keene JD. (1985) Isolation and analysis of cDNA clones expressing human lupus La antigen. Proc Natl Acad Sci USA 82, 2115–2119
Le Naour, F., Brichory, F., Beretta, L., Hanash, S.M. (2002) Identification of tumor-associated antigens using proteomics. Technol Cancer Res Treat 1, 257–262
Le Naour, F., Brichory, F., Misek, D.E., Brechot, C., Hanash, S.M., Beretta, L. (2002) A distinct repertoire of autoantibodies in hepatocellular carcinoma identified by proteomic analysis. Mol Cell Proteomics 1, 197–203
Shevchenko, A., Wilm, M., Vorm, O., Mann, M. (1996) Mass spectrometric sequencing of proteins silver-stained polyacrylamide gels. Anal Chem 68, 850–858
Acknowledgments
This work was supported by grants from National Institutes of Health (2S06GM008012-37, 5G12RR08124, CA56956).
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2009 Humana Press, a part of Springer Science+Business Media, LLC
About this protocol
Cite this protocol
Zhang, JY., Looi, K., Tan, E. (2009). Identification of Tumor-Associated Antigens as Diagnostic and Predictive Biomarkers in Cancer. In: Tainsky, M. (eds) Tumor Biomarker Discovery. Methods in Molecular Biology, vol 520. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-60327-811-9_1
Download citation
DOI: https://doi.org/10.1007/978-1-60327-811-9_1
Published:
Publisher Name: Humana Press, Totowa, NJ
Print ISBN: 978-1-60327-810-2
Online ISBN: 978-1-60327-811-9
eBook Packages: Springer Protocols