TIMP-1 Expression in Human Colorectal Cancer Is Associated with SMAD3 Gene Expression Levels: A Pilot Study

Abstract

Background & Aims: The prognosis of colorectal cancer (CRC) varies considerably, and there is a compelling need to identify novel biomarkers with prognostic significance. The aim of the present study was to evaluate the prognostic value of a panel of six genes (CDH1, SMAD3, TGFβ1, ICAM-1, TIMP-1 and MUC12) in CRC patients.

Methods. We evaluated these genes by qRT-PCR in normal and CRC tumor tissue, and correlated the relative gene expression values with clinical, pathological aspects and other biological factors.

Results. RNA expression levels of CDH1, SMAD3, TGFβ1, ICAM-1, TIMP-1 and MUC12 were measured by qRT-PCR in a set of 39 tumor samples and non-cancer tissue. Statistically significant increases in expression levels were found for ICAM-1 and TIMP-1 when comparing tumor samples to the non-tumor group.

Conclusions. Among the genes which displayed differential expressions between tumor tissue and adjoining normal tissue, the ones that presented statistically significant correlations were TIMP-1 and SMAD3, possibly with prognostic significance.

Abbreviations: CDH1: E-cadherin; CRC: colorectal cancer; E-cadherin: CDH1; EMT: epithelial-mesenchymal transition; IBD: inflammatory bowel disease; ICAM-1: Intercellular Adhesion Molecule 1; MMPs: matrix metalloproteinases; MUC12: Mucin 12, Cell Surface Associated; OS: overall survival; SMAD3: SMAD Family Member; TGFß1: Transforming growth factor beta 1; TIMP-1: tissue inhibitor of metalloproteinase-1.