Tumor Associated Antigen Proteins


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 Tumor Associated Antigen Proteins Background

Many studies have demonstrated that cancer sera contain antibodies against a unique group of autologous cellular antigens called tumor-associated antigens (TAAs). Autoantibodies to TAAs can be used as serological markers for early diagnosis of cancer. Cancer has long been recognized as a multi-step process which involves not only genetic changes conferring growth advantage but also factors which disrupt regulation of growth and differentiation as well as lead to altered expression patterns, modifications in protein structures and functions. In biochemical levels, cancer is contributed to by several groups of protein which work in malfunction or lose their normal ability in the human body. In the early stages, cancer causes no symptoms in the patients but the precancerous changes in a patient’s sera are detectable. The variation of tumor-associated antigens and their autoantibody appearance is the early signal for tumor development. It is possible that some of these factors could be identified and their functions evaluated with the aid of autoantibodies arising during tumorigenesis. Many investigators have been interested in the use of autoantibodies as serological markers for cancer diagnosis, especially because of the general absence of these autoantibodies in normal individuals and in non-cancer conditions. In addition, these autoantibodies have been detected in sera from patients with cancer, and significant advances have been made in the identification of their target antigens, particularly in lung cancer  and HCC. Although the mechanisms leading to autoantibody production in cancer patients are not clearly understood, emerging evidence indicates that most TAAs are cellular proteins whose aberrant regulation of function could be linked to malignancy.

 

Identification of TAAs

The establishment of panels of TAAs that elicit a humoral response can contribute highly to the development of methods in early screening and diagnosis of cancer. Several approaches are currently available for the identification of TAAs in cancer. One of the approaches is by using serum antibodies from cancer patients to immunoscreen cDNA expression library to identify TAAs in cancer, and some of these identified TAAs may have potential diagnostic values in cancer diagnosis. Using this approach, several novel TAAs such as p62 and p90 have been isolated in previous studies. Another approach of proteome-based technology has recently been implemented for identifying TAAs in cancer.

Over the past decade, proteomic techniques have been established in the field of cancer research to study basic and clinical aspects of cancer research. These new technologies are also being applied to facilitate the identification of novel diagnostic markers for cancer. In particular, there has been a remarkable advance in the field of proteomics over the last few years. Proteomics has the potential to discover and further expand the genetic information generated by genomics in liver cancer for several reasons. Compared to the first approach, which we have previously used, the proteome-based methodology allows individual screening of a large number of sera, as well as determination of a large number of autoantigens. The proteome-based approach can also distinguish isoforms and the detection of autoantibodies directed against post-translational modifications (PTMs) of specific targets. It is well known that mRNA levels do not necessarily correlate with corresponding protein abundance. Additional complexity of protein is conferred by PTMs including phosphorylation, acetylation, and glycosylation, as well as protein cleavage. These modifications may not reflect any change at the mRNA level but play important roles in protein stability, activity and functions. Intracellular proteins may also participate in the transformation of a healthy cell into a neoplastic cell. Therefore, protein levels may be more accessible and relevant to therapeutic targets than mRNA levels.