DNA promoter methylation status and protein expression of interleukin-8 in human colorectal adenocarcinomas

Interleukin-8 (IL-8) also referred to as CXCL8, a member of the CXC chemokine family that attracts neutrophils and other leukocytes, has been associated with cancer. Angiogenesis is a prime regulator of tumour expansion and data support that IL-8 is a potent angiogenic factor. Epigenomic instability has been postulated to play a role for the development of multiple neoplasias including colorectal cancer (CRC). DNA methylation of cytosine residues in CpG dinucleotides leads to transcriptional silencing of associated genes.

In this study, we comparatively analysed the protein expression of IL-8 in plasma, tumour and paired normal tissue and methylation status of the IL-8 gene to evaluate its impact on CRC.

Collectively, by using Luminex technology, we noted a significantly higher IL-8 level in cancer tissue compared to paired normal tissue and that CRC patients exhibit significantly higher plasma levels than healthy controls. Analysed by methylation-specific polymerase chain reaction, we detected IL-8 hypomethylation in 64% of the cancerous tissue cases but no hypomethylation was found in paired normal tissue. We noted that the CRC patients with IL-8 hypomethylation revealed a significant higher level of IL-8 protein in cancerous tissue, which tended to be associated with distant metastasis. We also observed that patients with distant metastasis showed a significantly higher plasma level of IL-8 in relation to patients without distant metastasis.

Our results suggest that the predominance of high plasma levels of IL-8 in patients with distant metastasis in combination with the hypomethylation of the IL-8 promoter region might be a useful marker of the disease advancement.