Hironobu Baba1, Toshiaki Ishikawa2, Kaoru Mogushi3, Megumi Ishiguro4, Hiroyuki Uetake4, Hiroshi Tanaka3, Kenichi Sugihara1. 1. Department of Surgical Oncology, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan. 2. Department of Surgical Oncology, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan ishi.srg2@tmd.ac.jp. 3. Department of Systems Biology, Graduate School of Biochemical Science, Tokyo Medical and Dental University, Tokyo, Japan. 4. Translational Oncology, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan.
Abstract
BACKGROUND/AIM: The integration of gene expression analysis and genomic profiling represents an efficient approach to the discovery of cancer-related genes. Lymph node metastasis (LNM) is a significant prognostic factor in colorectal cancer (CRC). Detection and analysis of factors related to LNM will help develop new diagnostic methods or therapies. In this study, we aimed to identify genes that are significantly related to LNM in CRC through integrated copy number analysis (CNA) and gene expression analysis. MATERIALS AND METHODS: Genes showing both up-regulated expression and copy number gains in cases involving CRC with LNM were extracted as candidate biomarkers. Expression of the mRNA of the final candidate was validated in 124 patients using quantitative reverse transcription polymerase chain reaction (qRT-PCR) assays. Expression of the protein encoded by this candidate gene was assessed using immunohistochemical (IHC) staining of tissueσ from 328 patients. The association between protein expression and clinicopathological features was also examined. RESULTS: Special AT-rich sequence-binding protein 1 (SATB1) was extracted from integrated microarray analysis. SATB1 mRNA expression in cancer tissue was significantly higher in patients with LNM than without LNM. SATB1 protein overexpression was significantly associated with LNM. Moreover, overexpression of SATB1 was an independent poor prognostic factor in stage I-III, especially in stage II CRC. CONCLUSION: SATB1 may play an important role in LNM of CRC. SATB1 may be a biomarker of LNM and of recurrence after surgery for CRC. Copyright
BACKGROUND/AIM: The integration of gene expression analysis and genomic profiling represents an efficient approach to the discovery of cancer-related genes. Lymph node metastasis (LNM) is a significant prognostic factor in colorectal cancer (CRC). Detection and analysis of factors related to LNM will help develop new diagnostic methods or therapies. In this study, we aimed to identify genes that are significantly related to LNM in CRC through integrated copy number analysis (CNA) and gene expression analysis. MATERIALS AND METHODS: Genes showing both up-regulated expression and copy number gains in cases involving CRC with LNM were extracted as candidate biomarkers. Expression of the mRNA of the final candidate was validated in 124 patients using quantitative reverse transcription polymerase chain reaction (qRT-PCR) assays. Expression of the protein encoded by this candidate gene was assessed using immunohistochemical (IHC) staining of tissueσ from 328 patients. The association between protein expression and clinicopathological features was also examined. RESULTS:Special AT-rich sequence-binding protein 1 (SATB1) was extracted from integrated microarray analysis. SATB1 mRNA expression in cancer tissue was significantly higher in patients with LNM than without LNM. SATB1 protein overexpression was significantly associated with LNM. Moreover, overexpression of SATB1 was an independent poor prognostic factor in stage I-III, especially in stage II CRC. CONCLUSION:SATB1 may play an important role in LNM of CRC. SATB1 may be a biomarker of LNM and of recurrence after surgery for CRC. Copyright