Researchers at University of California, San Diego School of Medicine, Columbia University and Stanford University have discovered a distinctive molecular feature that identifies colon cancer patients who are most likely to remain disease-free up to five years after surgery.
The biomarker, a protein called CDX2, also helped the researchers identify Stage II colon cancer patients who are most likely to benefit from chemotherapy after surgery.
“Because previous studies did not take into account differences between colon cancers with and without CDX2, doctors have long struggled to identify which Stage II colon cancer patients might benefit from adjuvant chemotherapy,” said first author Debashis Sahoo, PhD, assistant professor of pediatrics, and computer science and engineering at UC San Diego. “But what we’ve now found is that some of these patients might benefit from chemotherapy, and we now have a biomarker to tell the difference, potentially saving many lives and reducing toxicity from unnecessary treatment.”
Sahoo led the study alongside co-author Piero Dalerba, MD, of Columbia University, and senior author Michael Clarke, MD, of Stanford University.
The study took advantage of a method developed by Sahoo to identify differences in gene expression patterns. Sahoo used it earlier to find genes involved in stem cell differentiation, the process in which stems cells specialize into specific cell types in an organ.
“Dr. Sahoo’s bioinformatics approach is extraordinarily powerful,” said Dalerba. “We used it to search for biomarkers that could help us identify which colon tumors were likely to contain high numbers of stem-like cells.”
Dalerba and Sahoo discovered that when the gene CDX2 is ‘off,’ another molecular marker in colon tumors, called ALCAM, is always ‘on.’
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“We reasoned that colon tumors lacking CDX2 would likely contain a higher number of stem-like cells, and would therefore be more aggressive than CDX2-positive tumors,” said Dalerba.
After analyzing a database of cancer gene expressions, the team found that 4 percent of colon cancers lack CDX2. They then used the database to determine if there is an association between CDX2 status and patient outcomes.
The team discovered that CDX2-negative tumors were associated with poorer prognosis. Forty-one percent of colon cancer patients with CDX2-negative tumors survived five years disease-free, as compared to 74 percent of patients with CDX2-positive colon tumors.
The team found that treating CDX2-negative patients with chemotherapy improved their chances of survival. Ninety-one percent of CDX2-negative Stage II colon cancer patients survived five years disease-free when they were treated with chemotherapy. In contrast only 56 percent of CDX2-negative Stage II colon cancer patients who did not receive chemotherapy survived five years disease-free.
“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, randomized clinical trials,” Sahoo said.
The retrospective study was published January 21 by the New England Journal of Medicine.
