Trypsin inhibitors

A trypsin inhibitor is a type of serine protease inhibitor that reduces the biological activity of trypsin. Trypsin is an enzyme involved in the breakdown of many different proteins, including as part of digestion in humans and other animals. As a result, protease inhibitors that interfere with its activity can have an antinutritional effect.

A study revealing that a protease inhibitor from the eggs of the freshwater snail Pomacea canaliculata, interacting as a trypsin inhibitor with the protease of potential predators, was reported in 2010, the first direct evidence for this mechanism in the animal kingdom.

The peptide tumor-associated trypsin inhibitor (TATI) has been used as a marker of mucinous ovarian carcinoma, urothelial carcinoma, and renal cell carcinoma. TATI is metabolised by the kidneys and is, thus, elevated in patients with renal failure. It may be elevated in nonneoplastic processes such as pancreatitis and can be used as a prognostic marker in this setting (levels above 70 micrograms/L are associated with poor prognosis).

Fifty percent of stage I mucinous ovarian carcinomas are associated with elevated TATI, and nearly 100% of stage IV tumors show elevated TATI.

Eighty-five to 95% of pancreatic adenocarcinomas are associated with increased TATI (but elevation in pancreatitis limits the clinical utility of TATI in this setting; see above).

Sixty percent of gastric adenocarcinomas show elevated TATI, in particular tumors of diffusely infiltrative/signet ring type. TATI, thus, complements CEA, which is elevated exclusively in intestinal type adenocarcinoma of the stomach.

In urothelial carcinoma, TATI expression varies with stage, ranging from 20% in low-stage tumors to 80% of high-stage tumors.

TATI sensitivity in the setting of renal cell carcinoma is approximately 70%. Elevated TATI is more likely to be seen in patients with advanced-stage disease.

In nearly all tumor types studied, TATI is a marker of poor prognosis.

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