Clinical significance of UNC5B Expression in Colorectal Cancer
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE22598 | GEO | 2011/12/04
SECONDARY ACCESSION(S): PRJNA128377
REPOSITORIES: GEO
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Project description:Distant metastasis is the major causes of death in colorectal cancer (CRC) patients. In order to identify genes influencing the prognosis of patients with CRC, we compared gene expression in primary tumors with and without distant metastasis using an oligonucleotide microarray. We also examined the expression of the candidate gene in 100 CRC patients by quantitative real-time reverse transcription PCR and studied the relationship between its expression and the prognosis of patients with CRC. As a result, we identified MUC12 as a candidate gene involved in metastasis processes by microarray analysis. Quantitative real-time reverse transcription PCR showed that MUC12 expression was significantly lower in cancer tissues than in adjacent normal tissues (P < 0.001). In stage II and stage III CRC, patients with low expression showed worse disease-free survival (P = 0.038). Multivariate analysis disclosed that MUC12 expression status was an independent prognostic factor in stage II and stage III CRC (relative risk, 9.532; 95% confidence interval, 2.303-41.905; P = 0.002). This study revealed the prognostic value of MUC12 expression in CRC patients. Moreover, our result suggests MUC12 expression is a possible candidate gene for assessing postoperative adjuvant therapy for CRC patients. Total of 111 microarray datasets (77 for LCM samples, and 17 pairs for homogenized samples from tumor and adjacent tissues) were normalized using robust multi-array average (RMA) method under R 2.6.2 statistical software together with BioConductor package, as described previously. Then, the gene expression levels were log2-transformed, and 62 control probe sets were removed for further analysis. In order to identify a set of genes associated with development of metastatic recurrence, we performed Wilcoxon rank-sum test for gene expression differences of 54,613 probe sets between recurrence and non-recurrence groups. Similarly, Wilcoxon singed-rank test was conducted to select genes which showed significant expression difference between tumor and adjacent tissue. Then, we selected a set of genes that satisfied both of above two criteria.
2010-03-05 | E-GEOD-18105 | biostudies-arrayexpress
Project description: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.
2012-10-16 | E-GEOD-27910 | biostudies-arrayexpress
Project description: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.
2012-10-16 | GSE27910 | GEO
Project description: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.
2012-10-16 | GSE27854 | GEO
Project description: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. Total 115 microarray datasets obtained from LCM samples of colorectal cancer patients were normalized using robust multi-array average (RMA) method under R statistical software version 2.12.1 together with BioConductor package. The normalized gene expression levels were presented as log2-transformed values by RMA, and 62 control probe sets were removed for further analysis. This submission represents the transcriptome component of the study.
2012-10-16 | E-GEOD-27854 | biostudies-arrayexpress
Project description:Distant metastasis is the major causes of death in colorectal cancer (CRC) patients. In order to identify genes influencing the prognosis of patients with CRC, we compared gene expression in primary tumors with and without distant metastasis using an oligonucleotide microarray. We also examined the expression of the candidate gene in 100 CRC patients by quantitative real-time reverse transcription PCR and studied the relationship between its expression and the prognosis of patients with CRC. As a result, we identified MUC12 as a candidate gene involved in metastasis processes by microarray analysis. Quantitative real-time reverse transcription PCR showed that MUC12 expression was significantly lower in cancer tissues than in adjacent normal tissues (P < 0.001). In stage II and stage III CRC, patients with low expression showed worse disease-free survival (P = 0.038). Multivariate analysis disclosed that MUC12 expression status was an independent prognostic factor in stage II and stage III CRC (relative risk, 9.532; 95% confidence interval, 2.303-41.905; P = 0.002). This study revealed the prognostic value of MUC12 expression in CRC patients. Moreover, our result suggests MUC12 expression is a possible candidate gene for assessing postoperative adjuvant therapy for CRC patients.
2010-02-04 | GSE18105 | GEO
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.
2011-02-28 | GSE21510 | GEO
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.
2011-02-28 | E-GEOD-21510 | biostudies-arrayexpress
Project description:Introduction: The potential of expression profiling using microarray analysis as a tool to predict the prognosis for different types of cancer has been realized. This study aimed to identify a novel biomarker for colorectal cancer (CRC). Experimental design: The expression profiles of cancer cells in 153 patients with CRC were examined using laser microdissection and oligonucleotide microarray analysis. Overexpression in CRC cells, especially in patients with distant metastases, was a prerequisite to select candidate genes. We analyzed the protein expression and localization of the candidate gene by immunohistochemical study and investigated the relationship between protein expression and clinicopathologic features in 271 CRC patients. Results: Using microarray analysis, we identified 11 candidate genes related to distant metastases in CRC patients. Among these genes, Traf2- and Nck- interacting kinase (TNIK) was known to be associated with aggressiveness in CRC through Wnt signaling. Absence of overexpression of TNIK protein was associated with significantly better overall survival (p < 0.001) and relapse-free survival (p < 0.001). Moreover, overexpression of TNIK protein was an independent risk factor for CRC recurrence (p = 0.009). Conclusion: Overexpression of TNIK might be a predictive biomarker of CRC recurrence. Copy number analysis was performed using LCM samples of 125 colorectal cancer patients by GeneChip Human Mapping 250k Sty arrays. Non-tumor tissues obtained from 47 patients were used as unpaired reference samples.
2015-11-21 | E-GEOD-64257 | biostudies-arrayexpress
Project description:Background: The potential of expression profiling using microarray analysis as a tool to predict the prognosis for different types of cancer has been realized. This study aimed to identify a novel biomarker for colorectal cancer (CRC). Methods: The expression profiles of cancer cells in 152 patients with stage I-III CRC were examined using microarray analysis. High expression in CRC cells, especially in patients with distant recurrences, was a prerequisite to select candidate genes. Thus, we identified eleven candidate genes, and selected Traf2- and Nck-interacting kinase (TNIK), which was known to be associated with progression in CRC through Wnt signaling pathways. We analyzed the protein expression of TNIK using immunohistochemistry (IHC) and investigated the relationship between protein expression and patient characteristics in 220 stage I-III CRC patients. Results: Relapse-free survival was significantly worse in the TNIK high expression group than in the TNIK low expression group in stage II (p = 0.028) and stage III (p = 0.006) patients. In multivariate analysis, high TNIK expression was identified as a significant independent risk factor of distant recurrence in stage III patients. Conclusion: This study is the first to demonstrate the prognostic significance of intratumoral TNIK protein expression in clinical tissue samples of CRC, in that high expression of TNIK protein in primary tumors was associated with distant recurrence in stage II and III CRC patients. This TNIK IHC study might contribute to practical decision-making in the treatment of these patients. Gene expression profiles for 152 cancer tissues from colorectal cancer patients were measured by Affymetrix HG-U133 Plus 2.0 arrays. Normalization was performed by robust multi-array average (RMA) method under R 2.12.1 statistical software with affy package from BioConductor. The normalized gene expression levels were presented as log2-transformed values by RMA.
2016-07-22 | E-GEOD-71222 | biostudies-arrayexpress