Clinical Significance of TROP2 Expression in Colorectal Cancer

• Published in: Clinical cancer research 2006-05, Vol.12 (10), p.3057-3063
• Main Authors: OHMACHI, Takahiro, TANAKA, Fumiaki, MIMORI, Koshi, INOUE, Hiroshi, YANAGA, Katsuhiko, MORI, Masaki
• Format: Article
• Language: English
• Subjects: Aged; Antigens, Neoplasm - biosynthesis; Antineoplastic agents; Biological and medical sciences; cDNA microarray; Cell Adhesion Molecules - biosynthesis; colorectal cancer; Colorectal Neoplasms - genetics; Colorectal Neoplasms - pathology; Epithelial Cells; Female; Gastroenterology. Liver. Pancreas. Abdomen; Gene Expression Profiling; Humans; Immunohistochemistry; laser microdissection; Liver Neoplasms - genetics; Liver Neoplasms - secondary; Male; Medical sciences; Middle Aged; Multivariate Analysis; Oligonucleotide Array Sequence Analysis; Pharmacology. Drug treatments; Prognosis; Reverse Transcriptase Polymerase Chain Reaction; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Survival Analysis; TROP2; Tumors
• ISSN: 1078-0432; 1557-3265
• DOI: 10.1158/1078-0432.CCR-05-1961

Purpose and Experimental Design: To identify cancer-related genes, the expression profiles of colorectal cancer cells and normal epithelial cells were examined and compared using laser microdissection and cDNA microarray analysis. From these combined techniques, several cancer-related genes, including TROP2 , were identified. TROP2 is known as a calcium signal transducer and is highly expressed in several types of tumors. However, no studies have investigated the significance of TROP2 expression in colorectal cancer. Thus, the expression status of TROP2 was investigated in 74 colorectal cancer samples by quantitative real-time reverse transcription-PCR and immunohistochemical studies. Results: Laser microdissection and cDNA microarray analysis showed that there were 84 overexpressed genes in cancer cells. One of the highly overexpressed genes was TROP2 . Quantitative real-time reverse transcription-PCR showed that TROP2 expression in cancer samples was significantly higher than in normal samples ( P < 0.001). The samples were divided into high ( n = 26) and low ( n = 48) TROP2 expression groups. The cases with high TROP2 expression showed a higher frequency of liver metastasis ( P = 0.005) and more cancer-related death ( P = 0.046). Those cases also had an inclination of deeper depth of invasion ( P = 0.064) and more lymph node metastasis ( P = 0.125). Interestingly, the patients with high TROP2 expression tumors had poorer prognosis ( P = 0.0036). Multivariate analysis showed that TROP2 expression status was an independent prognostic factor (relative risk, 2.38; 95% confidence interval, 1.29-4.74; P < 0.01). Conclusion: TROP2 is one of the cancer-related genes that correlates with biological aggressiveness and poor prognosis of colorectal cancer. Thus, TROP2 is a possible candidate gene for diagnosis and molecular target therapy of colorectal cancer.