Gene expression signature for recurrence in stage III colorectal cancers

• Published in: Cancer 2009-01, Vol.115 (2), p.283-292
• Main Authors: Watanabe, Toshiaki, Kobunai, Takashi, Sakamoto, Etsuko, Yamamoto, Yoko, Konishi, Tsuyoshi, Horiuchi, Atsushi, Shimada, Ryu, Oka, Toshinori, Nagawa, Hirokazu
• Format: Article
• Language: English
• Subjects: Adaptor Proteins, Signal Transducing; Biological and medical sciences; CABIN1; Calcineurin - genetics; colorectal cancer; Colorectal Neoplasms - genetics; copy number; Duke stage C; Gastroenterology. Liver. Pancreas. Abdomen; Gene Dosage; Gene Expression Profiling; Humans; lymph node metastasis; Lymphatic Metastasis; Medical sciences; microarray; Neoplasm Recurrence, Local - genetics; Polymerase Chain Reaction; prediction; recurrence; stage III; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; tailored therapy; Tumors
• ISSN: 0008-543X; 1097-0142
• DOI: 10.1002/cncr.24023

BACKGROUND: Colorectal cancer patients with lymph node metastases (stage III) show poorer prognosis than those without. Predicting development of recurrence may guide the need for intensive follow‐up and/or adjuvant chemotherapy in such patients. The authors' objective was to identify a set of discriminating genes that could predict recurrence in stage III colorectal cancer. METHODS: Thirty‐six stage III colorectal cancer patients were studied. Tumor samples were obtained from surgically resected specimens. Thirteen patients developed recurrence, whereas 23 patients did not. Gene expression profiles were determined using human HG‐U133 Plus 2.0 Gene Chip (Affymetrix, Santa Clara, Calif). RESULTS: The authors identified 45 discriminating genes between patients with and without recurrence. By using this gene set, they established a new model to predict recurrence with an accuracy of 90.9%. The discriminating genes included calcineurin‐binding protein 1 (CABIN1), whose expression differed remarkably between patients with and without recurrence (P = .0073). The authors further examined the DNA copy number of CABIN1 and were able to show a significant relation with recurrence (P < .012). Patients having CABIN1 gene loss demonstrated a higher risk of recurrence (odds ratio, 18.8). DNA copy number of CABIN1 alone could predict recurrence with an accuracy of 80.0%. CONCLUSIONS: The results of the current study demonstrated that gene expression profiling is useful in predicting recurrence in stage III colorectal cancer. The authors identified CABIN1 among discriminating genes that may play a key role in the development of recurrence. These results may help to establish an individualized therapy for stage III colorectal cancer. Cancer 2009. © 2009 American Cancer Society. The study showed that gene expression profiling is useful in predicting recurrence in stage III colorectal cancer. The authors identified CABIN1 among discriminating genes that may play a key role in the development of recurrence.