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GSE2825
Rattus norvegicus
11 Downloadable Samples
Affymetrix Rat Expression 230A Array (rae230a)
Description
Idiosyncratic drug reactions (IDRs) cause significant morbidity and mortality. In an animal model of IDRs, 50-80% of Brown Norway rats exposed to D-penicillamine develop an autoimmune syndrome after several weeks of treatment. The symptoms of the IDR are similar to that observed in humans who take D-penicillamine. The mechanism of this reaction is unknown, and no effective biomarkers have been identified to predict susceptibility. We postulate that cell stress caused by drugs is required to initiate the response. We used a highthroughput approach to identify factors that might represent danger signals by profiling hepatic gene expression 6 h after dosing with D-penicillamine (150 mg/kg). Our results show that the drug-treated animals cluster into two distinct groups. One group exhibits substantial expression changes relative to control animals. The most significantly altered transcripts have a role in stress, energy metabolism, acute phase response, and inflammation. We used quantitative reverse transcriptase polymerase chain reaction to measure transcript levels in liver biopsies of 33 rats and found that resistant animals cluster together. This 'resistant' cluster of animals contains 87.5% (7/8) resistant animals but only 48% (12/25) 'sensitive' animals. This separation is statistically significant at the p 0.01 level.
Publication Title
Gene expression profiling in a model of D-penicillamine-induced autoimmunity in the Brown Norway rat: predictive value of early signs of danger.
Sample Metadata Fields
Sex, Specimen part, Treatment
View Samples- Rattus norvegicus
- 6 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
Tienilic acid (TA) was withdrawn from the US market due to numerous cases of liver necrosis. Two major hypotheses currently used to understand the mechanisms of idiosyncratic reactions such as TA-induced hepatotoxicity are the hapten and danger hypotheses. Both human cytochrome (CYP) P450 2C9 and the rat ortholog CYP 2C11 metabolize TA, and it was reported that a reactive metabolite of TA binds almost exclusively to these enzymes, thus acting as a mechanism-based inhibitor. TA-induced liver toxicity is associated with antibodies against CYP 2C9, thus TA appears to act as a hapten. However, if the binding were limited to CYP 2C, it is unlikely that this would lead to significant cell stress. Thus, if TA does not cause cell stress it would suggest that a drug does not have to generate a danger signal in order to cause an idiosyncratic drug reaction and acting as a hapten is sufficient. In order to test whether TA can cause cell stress, male Sprague Dawley rats were orally dosed with TA, and hepatic gene expression was profiled at 6 and 24 h after drug administration.
Publication Title
Changes in gene expression induced by tienilic Acid and sulfamethoxazole: testing the danger hypothesis.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 112 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Identification of NUCKS1 as a colorectal cancer prognostic marker through integrated expression and copy number analysis.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 146 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Purpose: This study aimed to identify a novel biomarker or a target of treatment for colorectal cancer (CRC).
Publication Title
Clinical significance of osteoprotegerin expression in human colorectal cancer.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 112 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Purpose: The purpose of this study is to identify a novel biomarker related with distant metastases of colorectal cancer (CRC).
Publication Title
Identification of NUCKS1 as a colorectal cancer prognostic marker through integrated expression and copy number analysis.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 103 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
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.
Publication Title
MUC12 mRNA expression is an independent marker of prognosis in stage II and stage III colorectal cancer.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 42 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Unearthing of silenced genes in colorectal cancer (CRC) is of great importance. We employed oligonucleotide microarray to find changes in global gene expression of five CRC cell lines. These were analyzed before and after treatment with the 5-aza-2'-Deoxycitidine. Expression of the responding genes was integrated with gene expression profiling generated by microarray analysis of matched colorectal tissue samples. Selected candidates were subjected to methylation-specific PCR (MSP) and real-time quantitative reverse transcription-PCR using CRC cell lines and paired tumor and normal samples from CRC patients. Sixty eight genes were re-expressed after 5-aza-2'-Deoxycitidine treatment and over-expressed in normal colorectal mucosa, including genes that were known to be methylated in CRC. After applying study selection criteria, we identified 16 potential genes. Two candidates were selected (ASPP1 and SCARA5). Among 15 CRC cell lines, methylation was identified in SCARA5 (20%). The methylation status of SCARA5 was subsequently investigated in 23 paired colorectal tissue samples; methylation was detected in 17%, respectively. Observed promoter methylation showed a tendency towards methylation in tumor-derived samples, in SCARA5 gene. Significant down expression of SCARA5 mRNA was observed in CRC cell lines and tumor tissues compared to adjacent normal tissues (P < 0.001 and P = 0.001, respectively). The use of genome-wide screening led to the identification of a group of candidate genes. Among them, SCARA5 was methylated and markedly down-regulated in CRC. SCARA5 gene may have a role in CRC tumorigenesis.
Publication Title
Screening for epigenetically masked genes in colorectal cancer Using 5-Aza-2'-deoxycytidine, microarray and gene expression profile.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 125 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Prognostic significance of Traf2- and Nck- interacting kinase (TNIK) in colorectal cancer.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 148 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
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.
Publication Title
Prognostic significance of Traf2- and Nck- interacting kinase (TNIK) in colorectal cancer.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 125 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
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.
Publication Title
Prognostic significance of Traf2- and Nck- interacting kinase (TNIK) in colorectal cancer.
Sample Metadata Fields
Specimen part
View Samples