Molecular biomarkers may help predict outcomes for stomach cancer patients

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Researchers at Rhode Island Hospital have identified two potential molecular markers that may predict outcomes for patients with stomach cancer, according to a study in the July 1 issue of Clinical Cancer Research.

Patients who had poor outcomes following surgery for stomach cancer also had extremely low amounts of two proteins, gastrokine 1 and 2 (GKN1 and GKN2), according to the investigators.

Steven Moss, MD, who led the study, and colleagues said their findings confirm previous research showing that once stomach cells become cancerous, they manufacture very low amounts of GKN1 and GKN2. However, this is the first known study to link the low protein levels with outcomes following stomach cancer surgery.

Researchers said their discovery could eventually help physicians better determine and individualize therapy for stomach cancer, including which patients should be offered chemotherapy and other treatments in addition to surgery.

After looking at tissue samples from more than 150 stomach cancer patients who had undergone surgery, the investigators discovered a near total suppression of GKN1 and GKN2 in the majority of patients, which was particularly evident in patients with the diffuse variant of stomach cancer. More than three-quarters of the patients had extremely low levels of GKN1 and 85 percent had nearly nonexistent levels of GKN2.

Furthermore, in those patients with the intestinal variant of stomach cancer, very low levels of GKN 1 or GKN 2 at the time of surgery were associated with a significantly worse outcome, the authors wrote. The median survival was about two years in these patients, compared to a survival of more than 10 years for patients with normal levels of GKN1 or GKN2.

"Unfortunately, stomach cancer is difficult to cure unless it's discovered early, but because the early stage of the disease has very few symptoms, the cancer is usually advanced by the time it's diagnosed," said Moss, a gastroenterologist with Rhode Island Hospital and an associate professor of medicine at the Warren Alpert Medical School of Brown University; both located in Providence, R.I.

"That's what makes our findings so significant, because if the potential markers identified in our study can help predict a patient's prognosis, we can decide right away which course of action to take and hopefully help patients live longer and more comfortably," Moss added.

Researchers do not yet know the exact function of GKN1 and GKN2. They said further studies are needed to demonstrate the mechanisms responsible for the loss of GKN1 and GKN2 in this patient population, as well as the clinical biomarker potential of these two proteins.