REG1A and its receptor EXTL3 signal the recurrence of colorectal cancer

CHICAGO – The over expression of two genes, REG1A and EXTL3 in the patients with colorectal tumors enhance the risk of recurrence, according to a new study from the Max Delbrueck Center in Berlin, Germany.

In this study, REG1A expression was also significantly higher in surgical biopsies taken from pre-cancerous colon polyps, or adenomas.

"The findings suggest that the two genes are significant prognostic markers and may eventually help in making decisions about management of colorectal adenomas and tumors," said principal investigator Wolfgang Kemmner, Ph.D., who is Surgical Oncology Research Group Leader at the Max Delbrueck Center.

Results were presented at the first meeting on Molecular Diagnostics in Cancer Therapeutic Development, organized by the American Association for Cancer Research.

The researchers analyzed tumor and normal tissue from 75 colorectal cancer patients who had undergone surgery but not yet received any other treatment. They discovered that REG1A (Regenerating Islet-Derived 1 Alpha) was overexpressed in tumor specimens compared to normal tissue. In general, its level of expression correlated with the length of time before the disease recurred--as REG1A expression levels increased, disease-free survival decreased.

Patients with higher expression levels also tended to have lower disease-specific survival, meaning less time before they died from their disease. In addition, REG1A expression was significantly higher in tumors with peritoneal carcinomatosis, a type of advanced cancer in which many small tumors develop on the abdominal cavity and linings. The other gene, EXTL3 (Exostoses (Multiple)-Like 3), which was examined in samples of 56 patients, also tended to be upregulated in peritoneal carcinomatosis and was a significant predictor of patient outcome. EXTL3 encodes the receptor to which the REG1A protein binds.

Turning to precancerous adenomas, the researchers compared adenoma tissue from 22 patients to colorectal mucosal tissue from 31 healthy individuals. REG1A expression was significantly higher in the adenomas. Taken together, the findings raise the possibility that the genes could help guide decisions regarding both treatment and prevention of the disease.

"On the one hand, determining REG1A and EXTL3 expression levels could eventually help show which surgical patients are at high risk for recurrence and thus need more aggressive treatment," Kemmner said. "In addition, REG1A expression may serve in molecular diagnosis of very early tumors not yet apparent from conventional histopathology."

Source-Eurekalert
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