Abstract
Background. While cancer/testis antigens (CTAs) are restricted in postnatal tissues to testes and germ line-derived cells, their role in cancer development and the clinical significance of their expression still remain to be better defined. Objective. The aim of this study was to investigate the level of CTA expression in colon samples from patients with colorectal cancer (CRC) in relation to patient clinical status. Methods. Forty-five patients with newly diagnosed colorectal cancer were included in the study. We selected a panel of 18 CTAs that were previously detected in CRC as well as some new gene candidates, and their expression was detected at the mRNA level by employing RQ-PCR. Additionally, we evaluated CTA expression in three colon cancer cell lines (CL-188, HTB-39, and HTB-37) after exposure to the DNA methylation-modifying drug 5-azacytidine. Results. We report that 6 out of 18 (33%) CTAs tested (MAGEA3, OIP5, TTK, PLU1, DKKL1, and FBXO39) were significantly (p < 0.05) overexpressed in tumor tissue compared with healthy colon samples isolated from the same patients. Conclusions. Moreover, we found that MAGEA3, PLU-1, and DKKL expression positively correlated with disease progression, evaluated according to the Dukes staging system. Finally, 5-azacytidine exposure significantly upregulated expression of CTAs on CRC cells, which indicates that this demethylation agent could be employed therapeutically to enhance the immune response against tumor cells.
MeSH terms
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Adult
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Aged
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Aged, 80 and over
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Antigens, Neoplasm / genetics
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Antigens, Neoplasm / metabolism*
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Biomarkers, Tumor / genetics
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Biomarkers, Tumor / metabolism*
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Cell Cycle Proteins / genetics
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Cell Cycle Proteins / metabolism
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Cell Line, Tumor
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Chromosomal Proteins, Non-Histone / genetics
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Chromosomal Proteins, Non-Histone / metabolism
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Colorectal Neoplasms / metabolism*
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Colorectal Neoplasms / pathology
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DNA Methylation
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F-Box Proteins / genetics
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F-Box Proteins / metabolism
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Female
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Humans
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Intercellular Signaling Peptides and Proteins / genetics
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Intercellular Signaling Peptides and Proteins / metabolism*
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Jumonji Domain-Containing Histone Demethylases / genetics
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Jumonji Domain-Containing Histone Demethylases / metabolism*
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Male
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Middle Aged
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Neoplasm Proteins / genetics
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Neoplasm Proteins / metabolism*
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Nuclear Proteins / genetics
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Nuclear Proteins / metabolism*
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Protein Serine-Threonine Kinases / genetics
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Protein Serine-Threonine Kinases / metabolism
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Protein-Tyrosine Kinases / genetics
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Protein-Tyrosine Kinases / metabolism
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Repressor Proteins / genetics
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Repressor Proteins / metabolism*
Substances
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Antigens, Neoplasm
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Biomarkers, Tumor
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Cell Cycle Proteins
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Chromosomal Proteins, Non-Histone
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DKKL1 protein, human
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F-Box Proteins
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FBXO39 protein, human
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Intercellular Signaling Peptides and Proteins
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MAGEA3 protein, human
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Neoplasm Proteins
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Nuclear Proteins
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OIP5 protein, human
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Repressor Proteins
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Jumonji Domain-Containing Histone Demethylases
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KDM5B protein, human
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Protein-Tyrosine Kinases
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Protein Serine-Threonine Kinases
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TTK protein, human