Abstract
BackgroundNeoplastic transformation is a multistep process in which distinct gene products of specific cell regulatory pathways are involved at each stage. Identification of overexpressed genes provides an unprecedented opportunity to address the immune system against antigens typical of defined stages of neoplastic transformation. HER-2/neu/ERBB2 (Her2) oncogene is a prototype of deregulated oncogenic protein kinase membrane receptors. Mice transgenic for rat Her2 (BALB-neuT mice) were studied to evaluate the stage in which vaccines can prevent the onset of Her2 driven mammary carcinomas. As Her2 is not overexpressed in all mammary carcinomas, definition of an additional set of tumor associated antigens (TAAs) expressed at defined stages by most breast carcinomas would allow a broader coverage of vaccination. To address this question, a meta-analysis was performed on two transcription profile studies [1,2] to identify a set of new TAA targets to be used instead of or in conjunction with Her2.ResultsThe five TAAs identified (Tes, Rcn2, Rnf4, Cradd, Galnt3) are those whose expression is linearly related to the tumor mass increase in BALB-neuT mammary glands. Moreover, they have a low expression in normal tissues and are generally expressed in human breast tumors, though at a lower level than Her2.ConclusionAlthough the number of putative TAAs identified is limited, this pilot study suggests that meta-analysis of expression profiles produces results that could assist in the designing of pre-clinical immunopreventive vaccines.
Highlights
Neoplastic transformation is a multistep process in which distinct gene products of specific cell regulatory pathways are involved at each stage
The immune response may be addressed towards tumor associated antigens (TAAs) that are already present in early lesions and that remain overexpressed during the progression of the tumor [7]
This paper describes our application of meta-analysis to two BALB-neuT mice transcription profiling studies [1,2] to evaluate the possibility of identifying, within the tumor modulated genes, a set of new putative targets to be used as TAAs instead of or in conjunction with Her2
Summary
Neoplastic transformation is a multistep process in which distinct gene products of specific cell regulatory pathways are involved at each stage. As Her is not overexpressed in all mammary carcinomas, definition of an additional set of tumor associated antigens (TAAs) expressed at defined stages by most breast carcinomas would allow a broader coverage of vaccination To address this question, a metaanalysis was performed on two transcription profile studies [1,2] to identify a set of new TAA targets to be used instead of or in conjunction with Her. Despite of the fact that long lists of well-characterized TAAs recognized by T cells [3] and by antibodies [4] are currently available, the attempts to use them to arouse an immune response able to cure tumor patients has met with very little success, at least so far [5] Towards this goal significant obstacles are posed by the patient's state of immunosuppression and the numerous mechanisms to evade the immune response that a tumor progressively acquires [6].
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