EpHA2 Biomarker May Help Predict Prognosis in Colorectal Cancer Patients

Ephrin type-A receptor 2 (EpHA2), a protein that in humans is encoded by the EPHA2 gene, is a promising target that may help identify patients who are at risk for developing aggressive colorectal cancer (CRC).

This membrane-bound, erythropoietin-producing hepatocellular receptor tyrosine kinase is overexpressed in breast, brain, genitourinary, lung, ovarian, and skin cancers. But now researchers have discovered its presence in early-stage CRC clinical samples.

Findings were reported by Dr. Sonali Dasgupta, MD, of Queen's University Belfast, Centre for Cancer Research & Cell Biology, United Kingdom, at the 2014 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago (Abstract 3581). Dasgupta and colleagues found high EpHA2 levels in a panel of invasive colorectal cancer cells. Their goal was to investigate the prognostic value of EpHA2, and subsequently correlate expression levels to known pathological variables in early-stage CRC.

Tissue samples were obtained from 509 CRC patients to evaluate EpHA2 expression and was measured using IHC (immunohistochemistry). Researchers found that EpHA2 was overexpressed in CRC adenocarcinoma when compared to normal colon tissue. Furthermore, higher levels of EpHA2 were also associated with vascular invasion.

Another interesting finding to note was that higher levels of EpHA2 were detected in RAS and BRAF mutant CRC cells. Hence, silencing EpHA2 resulted in significant decreases in invasion among parental and invasive CRC sublines.

When broken down into disease stage, there was significant correlation between high EpHA2 expression and poor 5-years overall survival (OS) in stage II patients. This biomarker could help clinicians determine when aggressive treatment is necessary for those on the fence on whether to treat or not to treat stage II CRC.

While commercially available tests such as the Oncotype DX Colon Cancer Assay are used to help assess patients at high risk for CRC recurrence, there are no specifications as to how to actually treat the patient if they have a high predictor score. Having a drug that could specifically target EpHA2 in conjunction with a standard chemotherapy regimen may increase overall survival-and also help to take away some of the guess work in treating these early-stage CRC patients.

More clinical trials are needed to look at the value of EpHA2 in early-stage colorectal cancer, but so far the results look promising.

References:

Clinical Oncology. New Marker for Colon Cancer Identified. October 2014, Volume: 10.