Project description:This SuperSeries is composed of the following subset Series: GSE27854: Overexpression of NUCKS1 in colorectal cancer correlates with recurrence after curative surgery (gene expression analysis) GSE27910: Overexpression of NUCKS1 in colorectal cancer correlates with recurrence after curative surgery (copy number analysis) Refer to individual Series
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.
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.
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.
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.
Project description:Colorectal adenomas are common precancerous lesions with the potential for malignant transformation to colorectal adenocarcinoma. Endoscopic polypectomy provides an opportunity for cancer prevention, however, recurrence rates are high. We collected formalin-fixed paraffin-embedded tissue of fourteen primary adenomas with recurrence, fourteen primary adenomas without recurrence, and fourteen matched pair samples (primary adenoma and the corresponding recurrent adenoma). These samples were analysed by array-based comparative genomic hybridisation (aCGH) to understand the dynamics of copy number alterations (CNAs) and to identify molecular markers to predict recurrence. ACGH analysis confirmed the genetic landscape specific for colorectal tumorigenesis, i.e., CNAs of chromosomes 7 (13.7%), 13q (13.7%), 18 (5.8%) and 20q (13.7%). CNAs were detected in 41/51 (80.4%) of colorectal adenomas (2N). Focal aberrations (≤10 Mbp) were mapped to chromosome bands 6p22.1-p21.33 (33.3%), 7q22.1 (31.4%) and 16q21 (29.4%). Gains of CDX2 were exclusively seen in adenomas with recurrence compared to adenomas without recurrence. However, the average number of copy alterations failed to discriminate primary adenomas with recurrence from primary adenomas without recurrence.
Project description:Samples were taken from colorectal cancers in surgically resected specimens in 36 colorectal cancer patients. The expression profiles were determined using Affymetrix Human Genome U133 Plus 2.0 arrays. Comparison between the sample groups allow to identify a set of discriminating genes that can be used for molecular markers for predicting recurrence. Keywords: repeat Thirty-six colorectal cancer patients who had undergone surgical resection of colorectal cancer were studied. In all patients, curative resection was performed and no patients had any distant metastasis at the time of operation (stage III patients). Among the 36 patients, 23 patients did not develop recurrence. On the other hand, 13 patients developed rucurrence such as liver metastases, lung metastases and distant lymph node metastases. The median follow up period was 4.5 years.
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.