Biomarker panel developed for early detection of esophageal cancer

A research team has developed and validated a four-protein serum biomarker panel that holds significant promise for early detection of esophageal cancer, a relatively rare but often deadly disease that has grown in incidence over the past several decades.

The four-protein panel, called B-AMP (biglycan, myeloperoxidase, annexin-A6, and protein S100-A9), is a simple, noninvasive, low-cost blood test. In the study, it identified esophageal cancer with a high classification accuracy of 87%. The researchers were led by Blair Jobe, MD, a surgical oncologist with Allegheny Health Network in Pittsburgh, Pennsylvania, and their work was published in Cancer (2014; doi:10.1002/cncr.28963)

The discovery represents a major step forward for both early detection and also the management of esophageal cancer, explained Jobe. The test is already being used in a clinical trial setting to monitor the course of esophageal cancer.

"Esophageal cancer patients often have few options available to fight this disease, and 5-year survival rates are extremely low at about 15%," said Jobe. "We've made progress in treating and monitoring patients with conditions that can progress to esophageal cancer, such as Gastroesophageal Reflux Disease (GERD), Barrett's esophagus, and high-grade dysplasia. Yet only a small minority of these patients develops life-threatening esophageal cancer. Better detection techniques are needed."

The incidence of esophageal cancer is rapidly rising: up to 600% higher than in the 1970s. Survival is better when the disease is detected early, but unfortunately most patients do not sense difficulty swallowing until a tumor is advanced.

The development of blood-based biomarkers has improved early detection and impacted treatment of such cancers as ovarian and prostate, but developing blood-based esophageal cancer biomarkers has been hampered by the difficulty in identifying a single conserved and universal tracking marker.

Using tissue data from the esophageal cancer progression sequence, the team selected biomarkers that have known cancer relevance and were upregulated. The selected biomarkers were tested in the blood serum and analyzed through novel mathematical modeling. Then, the team was able to combine relevant and strong individual biomarkers into a panel that is accurate and reliable in detecting esophageal cancer.

The team used tissue samples obtained from the Department of Pathology at the University of Pittsburgh, representing patients with Barrett's esophagus, high-grade dysplasia, and esophageal cancer. These samples were used to identify and select targets for blood testing with a global proteomics profiling platform. The candidate biomarkers were then tested in blood samples from patients with non-Barrett's esophagus GERD and esophageal cancer. The findings were validated in an independent but similar cohort assembled at Allegheny Health Network and Roswell Park Cancer Institute in Buffalo, New York.

Out of 3,777 identified tissue proteins, five were significantly elevated in the blood of patients with esophageal cancer compared with patients with non-Barrett's esophagus GERD. Mathematical modeling found that four of those five had predictive value.

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