Detecting gastric cancer early -- it's in the sugars
Gastric cancer kills more than 700,000 people each year, mostly in Latin America, Asia and Eastern Europe. Though the disease is quite treatable when caught early, symptoms are indistinct and late detection leads to high mortality. The five-year survival rate in the United States is 26.9 percent.
An international team of researchers led by UC Davis in collaboration with scientists in Mexico and South Korea have taken a first step towards identifying glycans — sugars attached to proteins — that could help clinicians diagnose gastric cancer before it becomes deadly. Their research was published in the journal Cancer Prevention Research.
Gastritis and gastric cancer, along with duodenal ulcers, often share a common origin — Helicobacter pylori infection, which affects as many as 50 percent of the world’s population. However, there is no reliable way to predict whether patients with the infection will only experience asymptomatic gastritis or go on to develop cancer.
“We showed statistically significant differences between the serum glycan profiles of patients with gastric cancer and those with gastritis,” said Jay Solnick, lead author and professor in the Center for Comparative Medicine at UC Davis. “This is the first time anyone has looked at whether serum glycans could be used to detect gastric cancer.”
Co-author Carlito Lebrilla, professor of analytical chemistry at UC Davis, added that better tests are essential to detecting these cancers.
“In gastric and other cancers, there are high false positive rates and unnecessary biopsies,” he said. “We want to minimize these unneeded procedures.”
In a complex process called glycosylation, enzymes attach glycans to proteins, preparing these glycoproteins to perform their specific jobs. However, cancer can alter these enzymes, changing which glycans are attached and altering protein function. These enzyme changes are roughly analogous to robots on an automobile assembly line that have been reprogrammed to neglect side mirrors or to spray two coats of primer and no paint.
Using 72 samples from patients in Mexico City, the researchers studied whether specific glycans in serum differed between patients with gastric cancer, gastritis or duodenal ulcers. The team used mass spectrometry and liquid chromatography to measure glycan levels in the different samples. In all, they found 19 significant glycan changes, including three that differentiated gastric cancer from gastritis.
"We found changes in glycosylation that were consistent with other cancers we’ve observed,” said Lebrilla. “While this study focused specifically on gastric cancer, glycan concentrations could potentially be used to predict other cancers, such as ovarian and lung.”
One interesting trait of H. pylori infection is that patients can develop duodenal ulcers or gastric cancer but rarely both. The researchers hoped to find glycan changes between these conditions that would account for the absence of gastric cancer in ulcer patients. For example, there might be protective glycans that prevent cancer development. However, they found no significant differences between these glycan profiles.
Now that the researchers have identified glycans that are expressed differentially in gastritis and gastric cancer, the next step is to determine whether these glycosylation changes can be used to predict cancer.
“Right now we have statistical significance but not predictive value,” said Solnick. “If we can improve the predictability, we could create a diagnostic test with real clinical value.”
Other authors included: Sureyya Ozcan, Donald A. Barkauskas, L. Renee Ruhaak, Javier Torres, Cara L. Cooke, Hyun Joo An, Serenus Hua, Cynthia C. Williams, Lauren M. Dimapasoc, Jae Han Kim, Margarita Camorlinga, David Rocke.
UC Davis collaborated with the Instituto Mexicano del Seguro Social and Chungnam National University.
This study was funded by the National Institutes of Health (R01 CA136647) and the Converging Research Center Program (2012K001505 for H. J. An) through the Korean Ministry of Education, Science and Technology.
UC Davis Comprehensive Cancer Center is the only National Cancer Institute-designated center serving the Central Valley and inland Northern California, a region of more than 6 million people. Its specialists provide compassionate, comprehensive care for more than 10,000 adults and children every year, and access to more than 150 clinical trials at any given time. Its innovative research program engages more than 280 scientists at UC Davis, Lawrence Livermore National Laboratory and Jackson Laboratory (JAX West), whose scientific partnerships advance discovery of new tools to diagnose and treat cancer. Through the Cancer Care Network, UC Davis collaborates with a number of hospitals and clinical centers throughout the Central Valley and Northern California regions to offer the latest cancer care. Its community-based outreach and education programs address disparities in cancer outcomes across diverse populations. For more information, visit cancer.ucdavis.edu.