Aim: Increased DNA methylation within the promoter regions of tumor suppressor genes has been associated with gene silencing in various cancers. CDX2, a caudal-related homeobox transcription factor, represents a key tumor suppressor in colorectal cancer. However, the pathological role of its promoter methylation has not yet been well defined in colorectal cancer.
Methods: We measured CDX2 promoter methylation by methylation-specific PCR (MSP) and CDX2 mRNA levels by real-time quantitative reverse transcription-PCR in both tumor and normal control tissues collected from 108 colorectal cancer patients and then performed correlation analyses. We also determined whether CDX2 promoter methylation status was associated with any clinicopathological features and prognosis in these patients.
Results: CDX2 was expressed in all normal mucosa, but only in 38 (35.2%) tumor tissues. CDX2 promoter methylation was detected in 43 (39.8%) tumor samples, but in none of the normal tissue specimens. DNA methylation correlated with decreased mRNA level in these tumors (p < 0.05). The methylation of the CDX2 promoter was associated with enhanced lymph node metastases and shorter survival time (p = 0.0273), but was independent of tumor stage, tumor differentiation, gender, and age.
Conclusion: Enhanced CDX2 promoter methylation is associated with gene silencing in a subgroup of colorectal cancer patients with lymph node metastasis and shorter survival times.
Keywords: CDX2; colorectal cancer; methylation.