Scientists Identify Biomarker for Chemotherapy Treatment

UCSD researchers, along with their colleagues at Columbia University and Stanford University, published a study on Jan. 29 in which they reported discovering a new protein biomarker in colon cancer patients that can help determine whether chemotherapy is beneficial to specific patients.

UCSD Assistant Professor of Pediatrics Debasish Sahoo led the five-month study along with his colleague Piero Dalerba of Columbia University and senior author of the study Michael Clarke from Stanford University. The hope of Sahoo and his colleagues was to develop a computerized model of cancer and use it to discover biomarkers to benefit medical research; they succeeded in finding that the protein CDX2 can help identify a smaller group of Stage-II colon cancer patients who would benefit from chemotherapy. Sahoo’s use of a bioinformatics approach allowed the team to differentiate gene expression patterns, and this found specific genes that take part in stem cell differentiation which allowed the team to find the biomarker CDX2.

Dalerba told the UCSD Guardian that Stage-II colon cancer can be cured through surgery. However, about 4 percent of patients require more specialized treatment.

“Our study found that a small subgroup of patients suffering from colon cancers who lack CDX2 expression appear to be at higher risk of relapse but also benefit from early treatment with adjuvant chemotherapy,” Dalerba said. “The scientific community agrees on the need to treat adjuvant chemotherapy patients with more advanced diseases [such as Stage-III patients with regional lymph-node metastases] but is still unsure about who, among Stage-II patients, would actually benefit from ‘adjuvant chemotherapy.’”

Sahoo also found that the method employed in this study, which combined data analysis and medical research, can improve medical studies and benefit all subjects.

“Our new discovery will most likely help us identify an aggressive form of colon cancer,” Sahoo told the Guardian. “It gives us strong evidence that the early-stage patients with this aggressive colon cancer may benefit from traditional chemotherapy.”

Dalerba explained that the research started off as a computer-assisted search for genes that were associated with a molecular marker known as activated leukocyte cell adhesion molecule.

“We found a list of candidate genes that fulfilled this condition and then ranked them based on the availability of diagnostic assays that could be used to test for their expression in primary tumors.” Dalerba said. “Only one of the candidate genes, the gene encoding for the transcription factor CDX2, fulfilled this requirement and was selected for further investigation.

There were two steps to completing this study. First the researchers identified candidate genes and then tested the association between the CDX2 expression, patient survival and benefits from adjuvant chemotherapy. The second part involved collecting and analyzing over 1,800 samples from multiple databases which is why the task took over five years to complete. 

Because this study was done by analyzing archives and microarray data sets rather than by patient clinical trials, there are were no effects on patients; however, the research team plans on confirming their findings using clinical trials with prospective and randomized patient cohorts.