Prognostic role of tumour associated trypsin inhibitor in colorectal cancer patients
type: CreativeWork
description: Colorectal cancer (CRC) is one of the most common forms of human cancer worldwide with approximately 1 million new cases detected every year. CEA is currently the only accepted CRC marker incorporated into clinical practice, where it is used for early detection of metastasis in follow-up of patients having stage II and III disease, and for monitoring response to adjuvant treatment. However there are no reliable prognostic and response predictive biomarkers for CRC. Tumour-associated trypsin inhibitor (TATI) is a form of antitrypsin, a 6kDa enzyme that inhibits trypsin with great affinity and TATI has previously been found to be of prognostic importance in mucinous ovarian cancer and other cancer forms. TATI is expressed in normal colonic mucosa, where its main function is to act as an antitrypsin, protecting the tissue from proteolysis. TATI has also been shown to promote migration and invasion in colorectal cancer cell lines in vitro. Moreover, TATI has a similar molecular structure to epidermal growth factor (EGF) and has been found to bind to EGFR and promote malignant behaviour in various cell line models. The prognostic significance of TATI in CRC patients had however not been reported and the main aim of the present investigation was therefore to examine levels of TATI in tumour tissue and serum samples from three independent CRC patient cohorts, with particular reference to their association with clinical outcome. In addition, we assessed the effect of neoadjuvant radiation therapy (RT) on TATI levels in tissue and serum of rectal cancer patients, and whether expression of epidermal growth factor receptor (EGFR) and markers of downstream signalling have a modifying effect on the prognostic value of TATI. In paper I, we investigated TATI expression by immunohistochemistry (IHC) in CRC tumours (t-TATI) in two cohorts adding up to 424 patients. High TATI expression was found to be significantly associated to short overall survival (OS), and disease free survival…
abstract: Colorectal cancer (CRC) is one of the most common forms of human cancer worldwide with approximately 1 million new cases detected every year. CEA is currently the only accepted CRC marker incorporated into clinical practice, where it is used for early detection of metastasis in follow-up of patients having stage II and III disease, and for monitoring response to adjuvant treatment. However there are no reliable prognostic and response predictive biomarkers for CRC. Tumour-associated trypsin inhibitor (TATI) is a form of antitrypsin, a 6kDa enzyme that inhibits trypsin with great affinity and TATI has previously been found to be of prognostic importance in mucinous ovarian cancer and other cancer forms. TATI is expressed in normal colonic mucosa, where its main function is to act as an antitrypsin, protecting the tissue from proteolysis. TATI has also been shown to promote migration and invasion in colorectal cancer cell lines in vitro. Moreover, TATI has a similar molecular structure to epidermal growth factor (EGF) and has been found to bind to EGFR and promote malignant behaviour in various cell line models. The prognostic significance of TATI in CRC patients had however not been reported and the main aim of the present investigation was therefore to examine levels of TATI in tumour tissue and serum samples from three independent CRC patient cohorts, with particular reference to their association with clinical outcome. In addition, we assessed the effect of neoadjuvant radiation therapy (RT) on TATI levels in tissue and serum of rectal cancer patients, and whether expression of epidermal growth factor receptor (EGFR) and markers of downstream signalling have a modifying effect on the prognostic value of TATI. In paper I, we investigated TATI expression by immunohistochemistry (IHC) in CRC tumours (t-TATI) in two cohorts adding up to 424 patients. High TATI expression was found to be significantly associated to short overall survival (OS), and disease free survival…
author: Gaber, Alexander
language: eng
keywords: Cancer and Oncology, KRAS mutation, ERK1/2, TATI, Colorectal cancer, Prognosis, Biomarker, EGFR, STAT3
date published: 2012
date modified: 2026-07-24T02:59:36Z
provider: University of Lund
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: Division of Pathology, Clinical Sciences, Lund