title: Identification of SATB1 as a Specific Biomarker for Lymph Node Metastasis in Colorectal Cancer.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  SATB1 may play an important role in LNM of CRC. SATB1 may be a biomarker of LNM and of recurrence after surgery for CRC.
authors.affiliation: Department of Surgical Oncology, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Hironobu
authors.initials: H
authors.lastname: Baba
authors.affiliation: Department of Surgical Oncology, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan ishi.srg2@tmd.ac.jp.
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Ishikawa
authors.affiliation: Department of Systems Biology, Graduate School of Biochemical Science, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Kaoru
authors.initials: K
authors.lastname: Mogushi
authors.affiliation: Translational Oncology, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Megumi
authors.initials: M
authors.lastname: Ishiguro
authors.affiliation: Translational Oncology, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Uetake
authors.affiliation: Department of Systems Biology, Graduate School of Biochemical Science, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Tanaka
authors.affiliation: Department of Surgical Oncology, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Sugihara
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000096:biosynthesis* / Q000235:genetics; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D056915:DNA Copy Number Variations / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008198:Lymph Nodes; D008207:Lymphatic Metastasis / Q000235:genetics* / Q000473:pathology; D008297:Male; D036961:Matrix Attachment Region Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D011379:Prognosis
chemical_list: D014408:Biomarkers, Tumor; D036961:Matrix Attachment Region Binding Proteins; C076189:SATB1 protein, human
keywords: Colorectal cancer; Special AT-rich sequence-binding protein 1 (SATB1); biomarker; microarray analysis; prognostic factor