Protein biomarker may signify aggressive colon cancer

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By Laura Sussman

MET protein levels correlate strongly with a cellular transition that occurs in a treatment-resistant type of colorectal cancer, according to new research from The University of Texas MD Anderson Cancer Center.

The study results, which compared MET protein expression with protein/gene expression of epithelial to mesenchymal transition (EMT) markers and evaluated impact on survival, were released today at the annual meeting of the American Society of Clinical Oncology in Chicago.

"When the epithelial cells that line the colon become cancerous, some of them develop special features to allow migration, causing the cancer to be more aggressive," says Kanwal Pratap Singh Raghav, M.D., fellow in MD Anderson's Division of Cancer Medicine. This transition from immobile epithelial cells to mobile mesenchymal cells is associated with cell migration and invasion, treatment resistance and metastasis.

"Although EMT is a dominant molecular subtype, a biomarker suitable for clinical use has not been found. This research gives us an important step toward learning more about treating this colorectal cancer subtype," Raghav says.

The study takes another step toward personalized cancer diagnosis and treatment.

"While we know there are many of types of colorectal cancer, we're not as advanced as we'd like to be in our understanding of them," says Scott Kopetz, M.D., Ph.D., associate professor in MD Anderson's Department of Gastrointestinal Medical Oncology and senior author of the study. "One of the larger goals of our research is to classify 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."

Data analysis reveals relationship

Researchers performed an exploratory analysis of 139 untreated primary colorectal cancer samples using data from The Cancer Genome Atlas, a joint effort of the National Cancer Institute, the National Human Genome Research Institute and institutions across the country to better understand cancer's molecular foundation.  Protein and gene expressions were measured using reverse-phase protein array (RPPA) and RNA-sequencing, respectively.

Higher MET levels were found more often in colon tumors than rectal tumors. Overexpression of MET was associated with:

·         Decreased overall survival

·         Higher gene expression of 28 EMT markers

·         Higher gene scores derived from three published EMT gene signatures

The group plans to apply this approach to other colorectal cancer subtypes, hopefully defining other simple and readily available biomarkers.

"The ultimate success in targeting colorectal cancer requires understanding molecular subsets of the disease," Kopetz says. "If we can identify and group cancers with similar behaviors, we'll be closer to identifying vulnerabilities and optimal therapies for each subset."

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