Abstract
Circulating autoantibodies against tumor-associated antigens (TAAs) and their pattern of glycosylation can be used as diagnostic indicators of cancer. Using random peptide library screening, we identified patient-specific sets of peptides recognized by colon cancer patients' serum IgG and IgM antibodies. We demonstrate a strategy for analyzing BLAST search results for identifying tumor-associated antigens represented by peptides that mimic sequential epitopes. Statistical analysis of the frequency with which the proteins are retrieved by BLAST homology searching and an estimation of the probability of a match by chance can identify the proteins that are the real targets of the immune response against tumors. In addition, we observed an over-expression of the mRNA for the match-producing protein only in the corresponding tumor sample, out of fourteen tumor and normal samples analyzed. This observation confirms that personalized tumor-associated antigens can be identified by BLAST homology search following random peptide library screening on cancer patient's serum antibodies.
Highlights
Tumor cells, often characterized by altered expression of proteins and their glycosylation patterns, induce humoral and cellular immune responses in the autologous host [1,2,3,4,5,6]
Our work demonstrates that for peptides that mimic sequential epitopes, the corresponding tumor-associated antigen (TAA) can be identified by protein database homology searches using the basic local alignment search tool (BLAST)
Multiple matches to different peptide sequences corresponding to antibodies from the same cancer patient strongly indicate the presence of an immune response against the protein retrieved by BLAST
Summary
Often characterized by altered expression of proteins and their glycosylation patterns, induce humoral and cellular immune responses in the autologous host [1,2,3,4,5,6]. TAAs have usually been identified by using cancer patients’ serum antibodies to screen cDNA libraries derived from autologous or heterologous tumors. Screening cDNA libraries, besides being laborious and time consuming, fails to identify TAAs generated by aberrant glycosylation of cell membrane glycoproteins and glycolipids [7]. An alternative to using cDNA expression libraries for TAA identification is to screen Random Peptide Phage Display Libraries (RPPDLs) with serum antibodies from cancer patients. Phage bound to the antibody are eluted and amplified in host bacteria. This process, termed “biopanning,” can be repeated several times in order to obtain an enriched population www.impactjournals.com/oncotarget
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