Research Holds Promise for Disease Management, Risk Assessment for Patients with GERD, Barrett’s Esophagus, Dysplasia and Esophageal Cancer

A research team led by Allegheny Health Network surgical oncologist Blair Jobe, MD, 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.

Dr. Jobe’s findings were published online in Cancer, a journal of the American Cancer Society.

The four-protein panel, called B-AMP (biglycan, myeloperoxidase, annexin-A6 and protein S100-A9), is a simple, non-invasive, low-cost blood test, that identified esophageal cancer with a high classification accuracy of 87 percent in the study.

The discovery represents a major step forward in not only early detection but also the management of esophageal cancer, said Dr. Jobe, Director of Allegheny Health Network’s Esophageal and Thoracic Institute. The test is already being used at the Institute 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 five-year survival rates are extremely low at about 15 percent,” said Dr. 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 develop life-threatening esophageal cancer. Better detection techniques are needed.”

The incidence of esophageal cancer is rapidly rising: up to 600 percent 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.

“We are excited and very optimistic about how this biomarker panel could be used to help patients, from early detection in at-risk patients, to risk-monitoring for patients with conditions that may lead to esophageal cancer, to monitoring the disease course in patients with cancer,” said Ali Zaidi, MD, Director of Research at the AHN Esophageal and Thoracic Institute.

The development of blood-based biomarkers has improved early detection and impacted treatment of cancers such as ovarian and prostate, but development of 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, biomarkers having known cancer relevance and which are upregulated, were selected for testing in the serum. Followed by novel mathematical modeling, Dr. Jobe’s 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; for identifying and selecting targets for blood testing using 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.

Out of 3,777 identified tissue proteins, five were shown to have significantly elevated levels in blood of patients with esophageal cancer, as compared to those with non-Barrett’s esophagus GERD, and on mathematical modeling four of those five were shown to have predictive value.

“Dr. Jobe’s research shows the value of our approach to working collaboratively and across the full spectrum of disease,” said David Parda, MD, System Chair, Allegheny Health Network Cancer Institute. “This tour de force research integrates clinical work and advanced biology/informatics to improve prevention, treatment, prognostic and predictive capabilities.”

Researchers from the Academic Medical Center in Amsterdam also participated in the study.