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Biomarker could predict which colon cancer patients respond to chemotherapy

Researchers have discovered a biomarker that could help to predict which stage II colon cancer patients will respond well to chemotherapy following surgery. The results of the study were published recently in the New England Journal of Medicine.

Surgery is an effective treatment for stage II colon cancer. However, approximately 15–20 % of these patients 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,” commented Piero Dalerba, first author of the paper of Columbia University Medical Center (NY, USA).

There are existing biomarkers to predict which stage II colon cancer patients are at higher risk of relapse after surgery; however, biomarkers to predict which patients would benefit from adjuvant chemotherapy are lacking.

The researchers focused on gene-expression patterns of cancer stem cells to search for new biomarkers – a technique developed by senior author Michael Clarke from Stanford University (CA, USA).

“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,” commented Dalerba.

To identify these tumors, the authors utilized a new bioinformatics approach designed by co-author Debashis Sahoo, from the University of California-San Diego (CA, USA). “In essence, we asked a computer the following question: can you help us find a gene whose lack of expression is always associated with high levels of cancer stem cell markers?” explained Sahoo.

The authors identified 16 potential biomarkers by analyzing data from in excess of 2000 cancer patients. Of these biomarkers, only a gene termed CDX2 was clinically actionable, as a standardized test for detecting the gene is already available.

CDX2 controls cell differentiation in the cells that line the colon, where the cancer starts. The team observed that patients whose tumors expressed CDX2 had a better prognosis compared with patients whose tumors did not express CDX2.

“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,” explained 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.”

Findings were similar in data taken from stage II colon cancer patients, whereby researchers found that patients with tumors lacking CDX2 expression were more likely to benefit from adjuvant chemotherapy than patients whose tumors did express the gene.

“What’s exciting is that an inexpensive, simple test for CDX2 expression is already widely available,” commented Dalerba.

The researchers noted that further studies are required before the biomarker can be utilized for making clinical decisions.

Source: Columbia University press release