Colorectal Cancer Linked to Reduced Levels of Hormone

Colorectal Cancer Linked to Reduced Levels of Hormone

The intestine-specific tumor suppressor GUCY2C is paradoxically overexpressed in colorectal cancer. Researchers have speculated that the counterintuitive observation reflects indirect silencing of GUCY2C by loss of the suppressor's paracrine hormone guanylin.

Using polymerase chain reaction assay technology, Waldman and colleagues examined guanylin levels in specimens from 281 patients with colorectal cancer and in matched adjacent normal tissue. Separately, they quantified guanylin levels by immunohistochemistry in 54 colorectal tumors and in 30 specimens of normal intestinal epithelium.

The results showed 100-fold variation in guanylin microRNA (mRNA) levels across the tissue specimens, including reductions of 100- to 1,000-fold in the vast majority of colorectal cancer specimens (P<0.001 versus adjacent normal tissue). The largest reductions in guanylin production occurred in patients younger than 50 (P<0.005) and in patients whose adjacent normal tissue had the highest expression of guanylin mRNA (P<0.001).

A validation analysis showed absence of guanylin protein in all 54 tumors evaluated by immunohistochemistry, but the hormone was present in all 30 samples of normal intestinal epithelium.

"Colorectal cancer may initiate as a disease of paracrine hormone insufficiency through loss of guanylin expression, silencing the GUCY2C tumor suppressor, and disrupting homeostatic mechanisms regulating colorectal epithelial cells," the authors concluded.

"Intestinal tumorigenesis may be prevented by oral GUCY2C hormone replacement therapy," they added.