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Biomarker Panel Could Improve Detection of Esophageal Cancer
Veronica Hackethal, MD
August 14, 2014
A 4-protein biomarker panel could improve the diagnosis of esophageal cancer, according to research published online August 5 in Cancer. The panel might also help guide treatment for those with the disease.
"We have [developed] a biomarker panel that is very inexpensive, highly accurate, and easy to use with just a blood test. We know from testing in independent samples that the test can determine the difference between those who have cancer and those who do not," said lead investigator Blair A. Jobe, MD, director of the Esophageal and Thoracic Institute at the Allegheny Health Network in Pittsburgh.
"We would like to see if we can use this biomarker panel to identify patients at an earlier stage. We haven't proven that yet, but that's our next step," Dr. Jobe told Medscape Medical News. "Our hope is that we'd be able to detect endoscopic changes in people who normally wouldn't have been endoscoped."
Clinical risk factors that could indicate whether a person is a good candidate for the test include obesity, long-term reflux disease requiring medication, tobacco use, and the presence of a large hiatal hernia, which can cause gastroesophageal reflux disease (GERD), Dr. Jobe explained.
For some time, doctors have needed a better diagnostic test for esophageal cancer — one that could either improve identification of patients at risk for the disease or aid in earlier diagnosis in those who already have it. Esophageal cancer has a high mortality rate, partly because diagnosis usually occurs at an advanced stage, when treatment is less effective.
In some patients, endoscopy screening is used to look for cancer or premalignant changes (Barrett's esophagus). However, this approach does not identify the majority of patients who develop esophageal cancer, according to Dr. Jobe, because this type of cancer is rare, compared with the number of people with GERD. In addition, screening completely misses a large percentage of people who develop esophageal cancer but who have never had GERD symptoms.
Discovery of the Biomarkers
To develop the panel, investigators at the University of Pittsburgh identified candidate biomarkers from tissue samples of patients with Barrett's esophagus, high-grade dysplasia, and esophageal cancer. They then used enzyme-linked immunosorbent assays (ELISAs) to compare levels of the identified biomarkers in the blood of 12 patients with esophageal cancer and 20 patients with GERD who were cancer-free.
To validate the biomarkers, the investigators tested them in 67 patients from outside institutions (Roswell Park Cancer Institute and the Allegheny Health Network in Buffalo, New York). The validation cohort consisted of 36 patients with non-Barrett's esophagus and GERD and 31 patients with esophageal cancer.
The investigators initially found high levels of 351 proteins in the tissue samples tested (P < .05). After performing ELISAs on 11, they identified 5 proteins at significantly higher concentrations in patients with esophageal cancer than in the patients with non-Barrett's esophagus and GERD. For 4 of these 5 proteins, concentrations were significantly higher in samples from patients with esophageal cancer than in patients with GERD who were cancer-free.
The 4 proteins that make up the biomarker panel, known as B-AMP, are biglycan, annexin A6, myeloperoxidase, and protein S100-A9.
Using a statistical model previously successful in developing biomarkers for amyotrophic lateral sclerosis and lung cancer, the investigators estimated that this biomarker panel would detect esophageal cancer with an accuracy of 87%.
The investigators are "cautious" in assuming that this biomarker panel will find every case of esophageal cancer, but results suggest it will identify the "majority" of cases, they report.
They note that the sample size in the study was small, and that the panel needs testing in a larger group of patients.
"We do have a patent on this, and our plan is to commercialize it," Dr. Jobe said, "but there is still some work to be done prior to doing that." A clinical trial is currently evaluating the use of the blood test in guiding therapy.
"Each tumor for each individual is entirely different from a biologic and genetic sense. Where we're headed in medicine is to better understand the vulnerabilities of a given tumor using genetic and genomic sequencing and targeted therapy," Dr. Jobe explained. "We see this biomarker assay as complementary to the emerging approach of personalizing care for patients, using our assay to help guide therapy and determine its effectiveness in real time and not wasting time for a patient who needs action immediately."
A provisional patent for this biomarker assay has been filed by the University of Pittsburg on behalf of Dr. Jobe and some of his coauthors, as detailed in the publication.
Cancer. Published online August 5, 2014. Abstract
Medscape Medical News © 2014 WebMD, LLC
Send comments and news tips to [email protected]
Cite this article: Biomarker Panel Could Improve Detection of Esophageal Cancer. Medscape. Aug 14, 2014.
Veronica Hackethal, MD
August 14, 2014
A 4-protein biomarker panel could improve the diagnosis of esophageal cancer, according to research published online August 5 in Cancer. The panel might also help guide treatment for those with the disease.
"We have [developed] a biomarker panel that is very inexpensive, highly accurate, and easy to use with just a blood test. We know from testing in independent samples that the test can determine the difference between those who have cancer and those who do not," said lead investigator Blair A. Jobe, MD, director of the Esophageal and Thoracic Institute at the Allegheny Health Network in Pittsburgh.
"We would like to see if we can use this biomarker panel to identify patients at an earlier stage. We haven't proven that yet, but that's our next step," Dr. Jobe told Medscape Medical News. "Our hope is that we'd be able to detect endoscopic changes in people who normally wouldn't have been endoscoped."
Clinical risk factors that could indicate whether a person is a good candidate for the test include obesity, long-term reflux disease requiring medication, tobacco use, and the presence of a large hiatal hernia, which can cause gastroesophageal reflux disease (GERD), Dr. Jobe explained.
For some time, doctors have needed a better diagnostic test for esophageal cancer — one that could either improve identification of patients at risk for the disease or aid in earlier diagnosis in those who already have it. Esophageal cancer has a high mortality rate, partly because diagnosis usually occurs at an advanced stage, when treatment is less effective.
In some patients, endoscopy screening is used to look for cancer or premalignant changes (Barrett's esophagus). However, this approach does not identify the majority of patients who develop esophageal cancer, according to Dr. Jobe, because this type of cancer is rare, compared with the number of people with GERD. In addition, screening completely misses a large percentage of people who develop esophageal cancer but who have never had GERD symptoms.
Discovery of the Biomarkers
To develop the panel, investigators at the University of Pittsburgh identified candidate biomarkers from tissue samples of patients with Barrett's esophagus, high-grade dysplasia, and esophageal cancer. They then used enzyme-linked immunosorbent assays (ELISAs) to compare levels of the identified biomarkers in the blood of 12 patients with esophageal cancer and 20 patients with GERD who were cancer-free.
To validate the biomarkers, the investigators tested them in 67 patients from outside institutions (Roswell Park Cancer Institute and the Allegheny Health Network in Buffalo, New York). The validation cohort consisted of 36 patients with non-Barrett's esophagus and GERD and 31 patients with esophageal cancer.
The investigators initially found high levels of 351 proteins in the tissue samples tested (P < .05). After performing ELISAs on 11, they identified 5 proteins at significantly higher concentrations in patients with esophageal cancer than in the patients with non-Barrett's esophagus and GERD. For 4 of these 5 proteins, concentrations were significantly higher in samples from patients with esophageal cancer than in patients with GERD who were cancer-free.
The 4 proteins that make up the biomarker panel, known as B-AMP, are biglycan, annexin A6, myeloperoxidase, and protein S100-A9.
Using a statistical model previously successful in developing biomarkers for amyotrophic lateral sclerosis and lung cancer, the investigators estimated that this biomarker panel would detect esophageal cancer with an accuracy of 87%.
The investigators are "cautious" in assuming that this biomarker panel will find every case of esophageal cancer, but results suggest it will identify the "majority" of cases, they report.
They note that the sample size in the study was small, and that the panel needs testing in a larger group of patients.
"We do have a patent on this, and our plan is to commercialize it," Dr. Jobe said, "but there is still some work to be done prior to doing that." A clinical trial is currently evaluating the use of the blood test in guiding therapy.
"Each tumor for each individual is entirely different from a biologic and genetic sense. Where we're headed in medicine is to better understand the vulnerabilities of a given tumor using genetic and genomic sequencing and targeted therapy," Dr. Jobe explained. "We see this biomarker assay as complementary to the emerging approach of personalizing care for patients, using our assay to help guide therapy and determine its effectiveness in real time and not wasting time for a patient who needs action immediately."
A provisional patent for this biomarker assay has been filed by the University of Pittsburg on behalf of Dr. Jobe and some of his coauthors, as detailed in the publication.
Cancer. Published online August 5, 2014. Abstract
Medscape Medical News © 2014 WebMD, LLC
Send comments and news tips to [email protected]
Cite this article: Biomarker Panel Could Improve Detection of Esophageal Cancer. Medscape. Aug 14, 2014.