EMMPRIN is associated with S100A4 and predicts patient outcome in colorectal cancer

• Published in: British journal of cancer Vol. 107; no. 4; pp. 667 - 674
• Main Authors: Boye, K, Nesland, J M, Sandstad, B, Haugland Haugen, M, Mælandsmo, G M, Flatmark, K
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 07.08.2012; Nature Publishing Group; Nature
• Subjects: 631/67/1059; 631/67/1857; 692/699/67/1504/1885; 692/700/1750; Adenocarcinoma - metabolism; Adenocarcinoma - mortality; Adenocarcinoma - pathology; Adult; Aged; Aged, 80 and over; Angiogenesis; Basigin - metabolism; Biological and medical sciences; Biomarkers; Biomarkers, Tumor - metabolism; Biomedical and Life Sciences; Biomedicine; Cancer Research; Cell Line, Tumor; Clinical outcomes; Colorectal cancer; Colorectal Neoplasms - metabolism; Colorectal Neoplasms - mortality; Colorectal Neoplasms - pathology; Drug Resistance; Enzymes; Epidemiology; Extracellular matrix; Female; Gastroenterology. Liver. Pancreas. Abdomen; Gene Knockdown Techniques; Humans; Male; Medical prognosis; Medical research; Medical sciences; Metastasis; Middle Aged; Molecular Diagnostics; Molecular Medicine; Neoplasm Staging; Oncology; Patients; Prognosis; Proteins; S100 Calcium-Binding Protein A4; S100 Proteins - metabolism; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Surgery; Tumors; Young Adult; Norway; EMMPRIN; prognostic biomarker; S100A4; colorectal cancer; Human; Rectal disease; Prognosis; Colorectal cancer; Biological marker; Malignant tumor; Colonic disease; Basigin; Cancerology; Digestive diseases; Intestinal disease; S100 calcium binding protein A4; Predictive factor; Cancer
• ISSN: 0007-0920; 1532-1827; 1532-1827
• DOI: 10.1038/bjc.2012.293

Background: Proteolytic enzymes and their regulators have important biological roles in colorectal cancer by stimulating invasion and metastasis, which makes these factors attractive as potential prognostic biomarkers. Methods: The expression of extracellular matrix metalloproteinase inducer (EMMPRIN) was characterised using immunohistochemistry in primary tumours from a cohort of 277 prospectively recruited colorectal cancer patients, and associations with expression of S100A4, clinicopathological parameters and patient outcome were investigated. Results: One hundred and ninety-eight samples (72%) displayed positive membrane staining of the tumour cells, whereas 10 cases (4%) were borderline positive. EMMPRIN expression was associated with shorter metastasis-free, disease-specific and overall survival in both univariate and multivariate analyses. The prognostic impact was largely confined to TNM stage III, and EMMPRIN-negative stage III patients had an excellent prognosis. Furthermore, EMMPRIN was significantly associated with expression of S100A4, and the combined expression of these biomarkers conferred an even poorer prognosis. However, there was no evidence of direct regulation between the two proteins in the colorectal cancer cell lines HCT116 and SW620 in siRNA knockdown experiments. Conclusion: EMMPRIN is a promising prognostic biomarker in colorectal cancer, and our findings suggest that it could be used in the selection of stage III patients for adjuvant therapy.