Genetic marker predicts colon cancer chemotherapy outcome

Scientists in the USA have identified a biomarker that could predict which patients with colon cancer might benefit from chemotherapy to prevent recurrences of the disease after surgical treatment.

Over 2000 patients with either stage II or III colon cancer were involved in the study, which looked at gene expression in cancer stem cells, as opposed to approaches that analyse a random sample of tumour cells. 

'We reasoned that tumours containing high numbers of cancer stem cells might be associated with a more aggressive disease, and wanted to find a way to easily find them,' said first author of the paper, Dr Piero Dalerba, assistant professor of medicine, pathology and cell biology at Columbia University Medical Centre (CUMC).

The researchers used computer software devised by Dr Debashis Sahoo, assistant professor of paediatrics at UC San Diego, to identify a gene which was not expressed in cancer stem cells, and for which a lack of expression was associated with high levels of cancer stem cell markers.

After analysing gene expression across patients, the researchers identified 16 genes that were not expressed while high levels cancer stem cell markers were present. Of these 16 genes, only one was shown to be clinically actionable, in that a diagnostic test for the expression of the gene already existed. This gene, called CDX2, is a regulator of cell differentiation in the lining of colon.

Lack of CDX2 had previously been associated with aggressive tumours that showed increased vascularisation and advanced stages of development. From patient data, the researchers found that the 87 patients whose tumours lacked CDX2 expression (CDX2-negative) had lower five-year survival rates than the 2028 patients with CDX2-positive tumours.

The researchers wanted to know whether the lower survival rates among CDX2-negative tumour patients were due to an intrinsic resistance to the chemotherapy treatments provided to some patients post-surgery to remove tumours.

However, the data showed that five-year survival rates were higher among patients with stage II CDX2-negative tumours who were treated with adjuvant chemotherapy – used in conjunction with surgery – than among patients who did not receive this post-surgery treatment.

Previous studies have identified biomarkers (distinctive features, such as lacking specific gene expression) of colon cancer. However, these could not be used to predict how patients might respond to treatment or which patients were at higher risks of relapse.

'What's exciting is that an inexpensive, simple test for CDX2 expression is already widely available,' said Dr Dalerba.

However, co-author Dr Sahoo said: 'While promising, this study was retrospective, meaning we looked back at existing patient data. Before they can be applied to clinical practice, these results need to be confirmed by prospective, randomised clinical trials.'