Identification of NUCKS1 as a colorectal cancer prognostic marker through integrated expression and copy number analysis

Akifumi Kikuchi, Toshiaki Ishikawa, Kaoru Mogushi, Megumi Ishiguro, Satoru Iida, Hiroshi Mizushima, Hiroyuki Uetake, Hiroshi Tanaka, Kenichi Sugihara

Research output: Contribution to journalArticlepeer-review

46 Citations (Scopus)

Abstract

We identified a novel prognostic biomarker for the distant metastasis of colorectal cancer (CRC) using comprehensive combined copy number and gene expression analyses. Expression of mRNA in CRC tissue was profiled in 115 patients using an Affymetrix Gene Chip, and copy number profiles were generated for 122 patients using an Affymetrix 250K Sty array. Genes showing both upregulated expression and copy number gains in cases involving distant CRC metastasis were extracted as candidate biomarkers. Expression of the candidate gene mRNA was validated in 86 patients using quantitative reverse transcription polymerase chain reaction assays. Expression of the protein encoded by the candidate gene was assessed using immunohistochemical staining of tissue from 269 patients. The relationship between protein expression and clinicopathologic features was also examined. Following combined copy number and gene expression analyses, three genes linked to distant metastasis of CRC were extracted as candidate biomarkers. The expression of NUCKS1, reportedly overexpressed in several cancers other than CRC, was significantly higher in CRC tissue than in normal tissue. Overexpression of the NUCKS1 protein in CRC cells was found to be associated with significantly worse overall survival and relapse-free survival, indicating that NUCKS1 is an independent risk factor for CRC recurrence. The overexpression of NUCKS1 in cancer cells could be used as a CRC prognostic marker and might also be a target for treatment of this disease. What's new The integration of gene expression analysis and genomic profiling represents an efficient approach to the discovery of cancer-related genes. Here, through a combination of gene expression and copy number analysis, NUCKS1 was identified as a candidate gene involved in the distant metastasis of colorectal cancer. The association of NUCKS1 protein overexpression with poor overall survival in colorectal cancer suggests that NUCKS1 may be a prognostic marker for the disease.

Original languageEnglish
Pages (from-to)2295-2302
Number of pages8
JournalInternational Journal of Cancer
Volume132
Issue number10
DOIs
Publication statusPublished - 2013 May 15

Keywords

  • DNA copy number analysis
  • biomarker
  • colorectal cancer
  • gene expression analysis
  • microarray

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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