Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Overexpression of NUCKS1 in colorectal cancer correlates with recurrence after curative surgery (copy number analysis)

ABSTRACT: Purpose: The purpose of this study is to identify a novel biomarker related with distant metastases of colorectal cancer (CRC). Experimental Design: We investigated mRNA expression profiles in 115 patients with CRC using an Affymetrix Gene Chip, and copy number profiles in 122 patients with CRC using an Affymetrix DNA Sty array. Genes in common between copy number and expression data were extracted as candidate genes. We analyzed the mRNA expression of candidate gene by quantitative reverse transcription polymerase chain reaction (RT-PCR) in 86 patients as a validation study. Furthermore, we analyzed the protein expression of candidate gene by immunohistochemical study in 269 patients, and investigated the relationship between protein expression and clinicopathologic features. Results: By the combination of copy number analysis and gene expression analysis, We extracted 2 candidate genes related with distant metastases of CRC. Several reports show that NUCKS1, one of candidate genes, is overexpressed in several cancer tissues. But a study about the relationship between NUCKS1 and CRC is none. The mRNA expression of NUCKS1 in cancer tissues was significantly higher than those in normal tissues. Overexpression of NUCKS1 protein was associated with significantly worse　relapse-free survival of CRC. Overexpression of NUCKS1 protein was an independent risk factor for recurrence of CRC. Conclusion: The overexpression of NUCKS1 would be a new biomarker predicting recurrence after colorectal surgery. Copy number analysis was performed using LCM samples of 122 colorectal cancer patients by GeneChip Human Mapping 250k Sty arrays. Non-tumor tissues obtained from 74 patients were used as unpaired reference samples.

ORGANISM(S): Homo sapiens

SUBMITTER: Kaoru Mogushi

PROVIDER: E-GEOD-27910 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

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

Kikuchi Akifumi A Ishikawa Toshiaki T Mogushi Kaoru K Ishiguro Megumi M Iida Satoru S Mizushima Hiroshi H Uetake Hiroyuki H Tanaka Hiroshi H Sugihara Kenichi K

International journal of cancer 20121105 10

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. ...[more]

PMID: 23065711

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Project description:Purpose: This study aimed to identify a novel biomarker or a target of treatment for colorectal cancer (CRC). Experimental Design: The expression profiles of cancer cells in 104 patients with CRC were examined using laser microdissection and oligonucleotide microarray analysis. Overexpression in CRC cells especially in patients with distant metastasis was a prerequisite to select candidate genes. The mRNA expression of candidate gene was investigated by quantitative reversetranscription polymerase chain reaction (RT-PCR) in 77 patients as a validation study. We analyzed the protein expression and localization of the candidate gene by immunohistochemical study, and investigated the relationship between the expression and the clinicopathological feature in 274 CRC patients. Results: We identified 6 genes as candidates related to distant metastasis in CRC patients by microarray analysis. Among these genes, Osteoprotegerin (OPG) is known to have an association with aggressiveness in several cancers through inhibiting apoptosis by neutralizing the function of tumor necrosis factor related apoptosis inducing ligand (TRAIL). The mRNA expression of OPG in cancer tissues was significantly higher in patients with distant metastasis than those without metastasis. The overexpression of OPG protein was significantly associated with worse overall survival and relapse free survival (RFS). Moreover, the overexpression of OPG protein was an independent risk factor for recurrence of CRC. Conclusion: The overexpression of OPG would be a predictive biomarker of recurrence and a target of the treatment for CRC. Total of 148 microarray datasets obtained from LCM and homogenized tissues of colorectal cancer patients were normalized using robust multi-array average (RMA) method under R 2.6.2 statistical software with affy package from BioConductor. Normalization was separately performed for LCM dataset and homogenized tissue dataset. The normalized gene expression levels were presented as log2-transformed values by RMA.

Dataset Information

Overexpression of NUCKS1 in colorectal cancer correlates with recurrence after curative surgery (copy number analysis)

Publications

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

Similar Datasets

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