CDX2 Expression Predictive of Chemotherapy Benefit in Patients With Stage II Colorectal Cancer

Lack of CDX2 expression identified a subgroup of patients with high-risk stage II colon cancer who seemed to benefit from adjuvant chemotherapy. This bioinformatics approach was published in the New England Journal of Medicine (doi:10.1056/NEJMoa1506597).

In colon cancer, stage II is defined as having grown into or through the outer layer of the colon but has not spread to lymph nodes or distant organs. A cure is achieved in most patients with this diagnosis with surgery alone, but approximately 15% to 20% eventually relapse and die of metastatic disease.

"The problem is that we don't have an easy way to single out these patients before they relapse and accurately predict who could benefit from postsurgical, or adjuvant, chemotherapy," said Piero Dalerba, MD, assistant professor of medicine, pathology and cell biology at Columbia University Medical Center (CUMC) and the Herbert Irving Comprehensive Cancer Center (HICCC) in New York, New York, and first author of the study.

This study sought potential biomarkers by focusing on cancer stem cells, which are the source of mature, or differentiated, tumor cells.

"We reasoned that tumors 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," Dalerba said. The researchers sought a gene whose lack of expression is always associated with high levels of cancer stem cell markers.

Data from more than 2,000 colon cancer patients were analyzed, resulting in 16 biomarkers being identified. Only one, the gene CDX2, was found to be clinically actionable, meaning a standardized diagnostic test to detect its expression is already available.

CDX2 regulates cell differentiation in the layer of cells that line the colon, where the cancer begins. The study found that patients whose tumors lacked CDX2 expression had a poorer prognosis compared with those whose tumors scored positive for CDX2 expression.

"We wanted to understand if the small group lacking CDX2 expression, approximately 4% of the global colon cancer population, fared poorly because of an intrinsic resistance to chemotherapy," said Dalerba. "To our surprise, we found that, on the contrary, tumors lacking CDX2 expression, despite being very aggressive from a biological point of view, also appeared to benefit from early treatment with adjuvant chemotherapy."

The more likely benefit from adjuvant chemotherapy for patients lacking CDX2 expression was held up when further analysis was done using data from the National Surgical Adjuvant Breast and Bowel Project.

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

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