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Colorectal cancer’s metastatic signature

‘Colorectal cancer’s metastatic signature’ – Written by Charlotte Harrison, Science Writer.

Epigenetic changes, such as DNA methylation, are linked to tumour metastasis and poor outcomes in cancers such as colorectal cancer (CRC). A new paper published in iScience has identified an epigenetic signature of CRC metastasis that, in the future, could be used to guide patient therapy and identify drugs that target the molecular drivers of metastasis.

 “How tumours become metastatic and so deadly, and what is different about these tumour cells remains largely unknown. The DNA instructions – the blueprint of a cell – and how and where these instructions go wrong in cancer cells provide important clues in understanding why this happens,” said the authors in a press release.

Expression changes

To identify epigenetic changes that occur in advanced CRC metastasis, the researchers performed whole-genome scale methylation and expression analysis in a well-defined set of paired patient samples of primary CRC and liver metastases.

Gene enrichment analysis revealed that the genes down-regulated in liver metastasis compared with CRC were mainly involved in gene silencing mechanisms and chromatin organisation, as well as the regulation of cell differentiation. The genes that were up-regulated were implicated in extracellular matrix organization and cell adhesion, as well as the regulation of haemostasis and response to wound healing.

Methylation differences

The researchers demonstrated that a subset of around 20 genes showed striking methylation differences between the primary and metastatic pairs, suggesting these changes might drive the expression of critical genes in the metastatic cascade.

Some of these genes have been described previously in CRC metastasis or been identified as markers of CRC diagnosis or prognosis. The methylation signature did not involve genes linked to the immune system.

Of note, the authors also identified several novel putative epigenetic drivers that have not been previously reported in CRC, namely C8orf82EFHD2SEC13SWI5 and ZC3H3.

With the aim of identifying therapeutic targets for inhibiting the metastatic spread of CRC and other cancers, the next step of research is to comprehensively validate this signature in other cancer types and metastatic sites.