Expression of nuclear factor Y, subunit C (NFY-C), and retinoic acid receptor-related orphan receptor alpha (RORA) in colorectal adenocarcinoma.

Abstract

e14085 Background: NFY-C gene is one of the three subunits of nuclear factor Y, a highly conserved transcription factor, which binds with high specificity to CCAAT motifs in the promoters of various genes. RORA is a member of the NR1 subfamily of nuclear hormone receptors. It can bind as a monomer or a homodimer to hormone response elements upstream of several genes to enhance their expression. Methods: mRNA levels of NFY-C and RORA were evaluated by quantitative RT-PCR in 81 neoplastic colorectal tissue specimens and 51 normal tissue specimens from patients with colorectal adenocarcinoma. All patients had undergone curative resections at the University Hospital of Patras, between 1995 and 2005. mRNA levels were normalised to the Alu-Sq levels and were analysed in relation to clinicopathological parameters. Protein expression of NFY-C was assessed by immunochemistry in 60 malignant and 20 normal samples from patients with colorectal adenocarcinoma. Results: There was a significant difference in the mRNA expression levels of NFY-C and RORA between normal and malignant tissues (p < 0.001 and p = 0.015, respectively). The mRNA levels of NFY- C and RORA were also related to the primary site of the tumor (p = 0.05 and p = 0.03, respectively). A 3-year survival benefit was also observed in patients with high expression levels of NFY-C (p = 0.023). There was no correlation between the mRNA levels of NFY-C or RORA and age, gender, grade, stage and relapse of the disease. However, mRNA levels of NFYC of stage B patients were significantly correlated with time to disease progression (p = 0.035). NFY-C protein was detected only in the cytoplasm both in malignant and normal tissues, with strong and weak intensity respectively. NFYC protein expression levels were correlated with mRNA expression levels of NFYC in malignant tissues (p = 0.011) and with the primary site of the tumour (p < 0.001). Conclusions: NFY-C and RORA exhibited elevated levels in colon carcinomas compared to normal tissue samples indicating a possible role for these molecules in colon carcinogenesis. The role of NFY-C and RORA in colorectal cancer warrants further investigation. No significant financial relationships to disclose.