From OncoLog, July 2013, Vol. 58, No. 7

In Brief

MET Protein May Serve as a Biomarker for a Treatment-Resistant Colorectal Cancer Subtype

The MET protein may be a surrogate indicator of the presence of the chemotherapy-resistant epithelial-mesenchymal transition (EMT) subtype of colorectal cancer, a recent study showed.

EMT occurs when epithelial cells change shape and lose cell-to-cell adhesion molecules, thereby allowing the cells to adopt certain characteristics of mesenchymal cells, such as invasiveness and resistance to cell death.

“We want to condense sophisticated gene signatures down to single markers and simple tests that can be used to guide therapy.”

– Dr. Scott Kopetz

Currently, the EMT subtype is identified by its genetic “signature”—multiple gene mutations. However, a single biomarker for this subtype has not been previously identified.

“While we know there are many types of colorectal cancer, we’re not as advanced as we’d like to be in our understanding of them,” said Scott Kopetz, M.D., Ph.D., an associate professor in the Department of Gastrointestinal Medical Oncology at The University of Texas MD Anderson Cancer Center. “One of the larger goals of our research is to find simple biomarkers that can be used by doctors in the community to identify subtypes. We want to condense sophisticated gene signatures down to single markers and simple tests that can be used to guide therapy.”

To determine whether MET protein could serve as a biomarker for EMT, Dr. Kopetz and his colleagues compared MET protein expression with the expression of proteins and messenger RNA for genes known to be altered in EMT. The researchers used data from The Cancer Genome Atlas to conduct an exploratory analysis of 139 untreated primary colorectal cancer samples.

Dr. Kopetz and his colleagues found that the expression of MET protein strongly correlated with the expression of the EMT-associated transcription factor Slug and of ERCC1, a marker for oxaliplatin resistance. High levels of MET protein expression also correlated with high expression levels of EMT-related genes. Higher levels of MET protein were associated with decreased overall survival durations. Colon tumors had higher levels of MET protein than rectal tumors did.

The results of this study may allow physicians to use MET protein expression as a biomarker for this often chemoresistant subtype of colorectal cancer. Dr. Kopetz and his colleagues presented their findings at the American Society of Clinical Oncology’s annual meeting in June.

For more information, talk to your physician, visit www.mdanderson.org, or call askMDAnderson at 877-632-6789.


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