Biomarkers Predict Prognosis of Esophageal Cancer Patients

Barrett’s esophagus, a chronic inflammatory condition that produces abnormal cells caused by gastroesophageal reflux, frequently precedes esophageal adenocarcinoma.

Barrett’s esophagus, a chronic inflammatory condition that produces abnormal cells caused by gastroesophageal reflux, frequently precedes esophageal adenocarcinoma.

New treatment strategies are needed to improve outcomes for patients with esophageal cancer. With five-year survival rates less than 25 percent, this is one of the deadliest forms of cancer. There are two main types of esophageal cancer—squamous cell carcinoma and adenocarcinoma. Esophageal adenocarcinoma is frequently preceded by Barrett’s esophagus, a chronic inflammatory condition caused by gastroesophageal reflux. It is known that communication between tumor cells and the immune system can alter the behavior of tumor cells, and chronic inflammation has been implicated in several types of human cancers, including cancer of the esophagus.

Based on the connections between esophageal cancer and inflammation, Giang Huong Nguyen, M.S., a predoctoral fellow working with Dr. Curt Harris, M.D., and colleagues in the CCR Laboratory of Human Carcinogenesis, designed a series of research studies to determine whether assessing the expression of inflammatory genes could help predict prognosis of patients with esophageal cancer. The results were published in a recent issue of Clinical Cancer Research.

The studies were conducted on tissues from a group of 93 patients with esophageal adenocarcinoma. Differences in expression of 23 inflammation-related genes were measured between tumorigenic and nontumorigenic esophageal tissue from the patients. Statistical analysis of the gene expression data from half of the patients—the so-called training cohort— was used to build an inflammatory risk model that could predict survival based on the patterns of expression of six genes. Patients with an elevated inflammatory risk score (IRS) had significantly shorter survival than those with a low IRS. The model was then tested on the other half of the patients—the test cohort—with similar results. The association of the IRS with prognosis was stronger among patients who had been diagnosed with Barrett’s esophagus prior to their cancer diagnosis.

The same research group recently discovered that levels of expression of a micro RNA called miR-375 were associated with survival in patients with Barrett’s-associated esophageal adenocarcinoma. Micro RNAs are short RNA molecules that do not code for proteins but often play a role in gene regulation. The researchers found that when considered together, the IRS and miR-375 measurements were better predictors of survival for patients with Barrett’s-associated adenocarcinoma than either measurement alone—patients with low IRS and high miR-375 had the best prognosis while those with high IRS and low miR-375 had the worst. When TNM staging, which includes information about tumor size as well as the presence of tumor cells in the lymph nodes and other sites in the body, was added to the model, the prognostic value was strengthened even further.

These findings indicate that the inflammatory genes and miR-375 together create an informative biomarker panel for patients with Barrett’s-associated esophageal adenocarcinoma. Although additional study is needed to confirm the findings in a larger group of patients, such a panel may assist in clinical management of esophageal cancer patients. In particular, the authors speculate that the multivariable assay might help identify individuals who may benefit from more aggressive adjuvant therapy in addition to surgery.

Summary Posted: Fri, 10/01/2010


Clin Cancer Res. 2010 Dec 1;16(23):5824-34. Epub 2010 Oct 14. Reviewed by Donna Kerrigan PubMed Link