Expression data from miRNAs in colorectal cancer tissues with and without liver metastasis
ABSTRACT: The purpose of this study is to identify miRNAs involved in the pathology of colorectal cancer (CRC) liver metastasis and investigate their underlying mechanisms. A total of 39 miRNAs were identified to be differentially expressed between 16 primary CRC tissues with liver metastases and 16 CRC tissues without liver metastases from 32 patients by Affymetric miRNA microarrays. 16 coloretcal cancer tissues with liver metastasis and 16 colorectal cancer tissues without liver metastasis were included in this study for RNA extraction and hybridization on Affymetrix microarrays. We sought to identify the differentially expressed miRNAs between colorectal cancer tissues with and without liver metastasis.
Project description:The purpose of this study is to identify lncRNAs involved in the pathology of colorectal cancer (CRC) liver metastasis and investigate their underlying mechanisms. A total of 439 miRNAs were identified to be differentially expressed between 7 primary CRC tissues with liver metastases and 8 CRC tissues without liver metastases from 15 patients by Arraystar lncRNA microarrays Overall design: 7 CRC with liver metastasis and 8 CRC without liver metastasis were subjected to microarray to select differentially expressed lncRNAs
Project description:In this study, we conducted a microarray-based analysis to identify differentially expressed miRNAs in CRC by comparing miRNA profiles among primary CRC tissues from patients with liver metastases, primary tissues without liver metastases, and liver metastatic lesions. microRNAs (miRNAs) have been shown to have a potential for cancer diagnosis lately. The main objective of this study is to identify a novel biomarker serum miRNA from the patients with colorectal cancer (CRC). Microarray analysis of miRNA expression was performed using paired pre- and post- operative serum from 10 CRC patients. Two miRNAs (let-7a, miR-199a-3p) decreased significantly in the post-operative serum when compared to pre-operative serum (P=0.015 and 0.029, respectively). Microarrays were performed for the testing cohort of primary CRC lesions (n=28) and liver metastatic lesions (n=8).
Project description:In this study, we conducted a microarray-based analysis to identify differentially expressed miRNAs in CRC by comparing miRNA profiles among primary CRC tissues from patients with liver metastases, primary tissues without liver metastases, and liver metastatic lesions. microRNAs (miRNAs) have been shown to have a potential for cancer diagnosis lately. The main objective of this study is to identify a novel biomarker serum miRNA from the patients with colorectal cancer (CRC). Microarray analysis of miRNA expression was performed using paired pre- and post- operative serum from 10 CRC patients. Two miRNAs (let-7a, miR-199a-3p) decreased significantly in the post-operative serum when compared to pre-operative serum (P=0.015 and 0.029, respectively). Overall design: Microarrays were performed for the testing cohort of primary CRC lesions (n=28) and liver metastatic lesions (n=8).
Project description:Liver metastasis is one of the major causes of death in colorectal cancer (CRC) patients. To understand this process, we investigated whether the gene expression profiling of matched colorectal carcinomas and liver metastases could reveal key molecular events involved in tumor progression and metastasis. We performed experiments using a cDNA microarray containing 17,104 genes with the following tissue samples: paired tissues of 25 normal colorectal mucosa, 27 primary colorectal tumors, 13 normal liver and 27 liver metastasis, and 20 primary colorectal tumors without liver metastasis. To remove the effect of normal cell contamination, we selected 4,583 organ-specific genes with a false discovery rate (FDR) of 0.0067% by comparing normal colon and liver tissues using significant analysis of microarray, and these genes were excluded from further analysis. We then identified and validated 46 liver metastasis-specific genes with an accuracy of 83.3% by comparing the expression of paired primary colorectal tumors and liver metastases using prediction analysis of microarray. The 46 selected genes contained several known oncogenes and 2 ESTs. To confirm that the results correlated with the microarray expression patterns, we performed RT-PCR with WNT5A and carbonic anhydrase II. Additionally, we observed that 21 of the 46 genes were differentially expressed (FDR = 2.27%) in primary tumors with synchronous liver metastasis compared with primary tumors without liver metastasis. We scanned the human genome using a cDNA microarray and identified 46 genes that may play an important role in the progression of liver metastasis in CRC. Keywords: gene expression profiling using cDNA microarray We performed 17K cDNA microarray with the amplified RNAs from the following tissue samples: normal colorectal mucosa, primary colorectal tumors, normal liver and liver metastasis tumors, and primary colorectal tumors without liver metastasis. Organ-specific genes in normal colon and liver tissues were excluded from the pre-filtered genes, and then we discovered and validated liver metastasis-specific genes commonly up-regulated in the primary colorectal tumors and liver metastasis tumors. To confirm the microarray data, we performed a RT-PCR of two genes (WNT5A and carbonic anhydrase II) in the primary colorectal tumors with and without liver metastases.
Project description:To identify potential metastasis associated miRNAs in colorectal cancer (CRC), we performed miRNA array on normal mucosa, CRC tissues without metastasis and CRC tissues with distant metastasis. Overall design: The miRNA expression in normal mucosa, CRC tissues without metastasis and CRC tissues with distant metastasis were analyzed using human miRNA Paraflo™ array (LC Sciences, CA, USA). Five clinical samples were pooled in each group.
Project description:Identifying the exact molecules associated with CRC metastasis may be crucial to understand the process, which might also be translated to the diagnosis and treatment of CRC. In this study, we investigate the association of microRNA expression patterns with the lymph node metastasis of colorectal cancer. To investigate the association of microRNA expression patterns with the lymph node metastasis of colorectal cancer, eight primary colorectal cancer tissues derived from stage II–III colorectal cancer patients with (n = 4) or without (n = 4) lymph node metastasis were collected and the miRNA expression profiles of them were determined using Agilent miRNA microarray. Different miRNA expression profiles were identified in CRC tissues between lymph node metastasis positive and negative group.
Project description:The aim of our study was to identify a microRNA signature for metastatic CRC that could predict and differentiate metastatic target organ localization. Normal and cancer tissues of three different groups of CRC patients were analyzed. RNA microarray and TaqMan Array analysis were performed on 66 italian patients with or without lymph nodes and/or liver recurrences. Data obtained with the two assays, were analyzed separately and then intersected to identify a primary CRC metastatic signature. Five differentially expressed microRNAs (hsa-miR-21, -103, -93, -31 and -566) were validated by qRT-PCR on a second group of 16 american metastatic patients. In situ hybridization was performed on the 16 american patients as well as on three distinct commercial tissues microarray (TMA), containing normal adjacent colon, the primary adenocarcinoma, normal and metastatic lymph nodes and liver. Hsa-microRNA-31,-21,-93, and-103 upregulation together with hsa-miR-566 downregulation defined the CRC metastatic signature, while in situ hybridization data identified a lymphonodal invasion profile. 33 patients had colon cancer with lymph nodes metastasis only (Any T, Any N, M0) and 15 were diagnosed with colon cancer, lymph nodes and liver metastases (Any T, Any N, M1). Separate tumor samples from the primary tumor, the metastatic lymph nodes and the liver metastasis were collected.
Project description:Background & Aims: The metastatic process is complex and remains a major obstacle in the management of colorectal cancer (CRC). To gain a better insight into the biologic events driving the metastatic process we investigated genomic aberrations in a large cohort of matched CRC primaries and distant metastases from various sites. Methods: In total, 62 primary colorectal cancers, 62 matched normal specimens, and 68 matched metastases (from liver, lung, ovary, omentum, and distant lymph nodes) were analyzed by high resolution array comparative genomic hybridization (array CGH) for DNA copy number changes. Findings were validated using a publicly available dataset consisting of 21 primary tumors and matched liver metastases. Fluorescence in situ hybridization (FISH) was used to confirm some of the DNA copy number changes observed. Results: Overall patterns of DNA copy number aberrations were highly similar between primary tumors and their metastases, confirming clonality. Additional copy number aberrations in metastasis are rare and rather than recurrent they were sporadic for individual patients. The only recurrent differences between primary tumors and their metastases were two chromosomal regions, 6q21 and 8q24.21 encompassing the MYC oncogene, that coamplified in three metastases of two patients (3.2%). FISH analysis confirmed the high level co-amplification in the metastasis, which were not detected in their primary tumors. Conclusions: Primary CRC and their metastases show highly similar patterns of DNA copy number changes, additional copy number aberrations in metastasis are rare and recurrences exceptional. These observations are consistent with the hypothesis that the metastatic potential is predestined early in the development of the primary tumor. In total, 62 primary colorectal cancers, 62 matched normal specimens, and 68 matched metastases (liver, lung, ovarian, omentum and distant lymph nodes) were analyzed by high resolution array comparative genomic hybridization (array CGH).
Project description:Comparison of genomic alterations of primary colorectal cancers with liver metastases of the same patient Keywords: array CGH, colorectal cancer, colon cancer, liver metastasis 21 primary colorectal cancers and 21 matched liver metastases hybridized against sex-matched control pools
Project description:PURPOSE: We sought to identify genes of clinical significance to predict survival and the risk for colorectal liver metastasis (CLM), the most common site of metastasis from colorectal cancer (CRC). PATIENTS AND METHODS: We profiled gene expression in 31 specimens from primary CRC and 32 unmatched specimens of CLM, and performed Significance Analysis of Microarrays (SAM) of the expressed genes between these two groups. To characterize the clinical relevance of two highly-ranked differentially expressed signature genes, we analyzed the expression of secreted phosphoprotein 1 (SPP1 or osteopontin) and lymphoid enhancer factor-1 (LEF1) by immunohistochemistry using a tissue microarray (TMA) representing an independent set of 154 patients with primary CRC. Supervised analysis using SAM identified 963 genes with significantly higher expression in CLM compared to primary CRC, with a false discovery rate of <0.5%. TMA analysis showed SPP1 and LEF1 protein overexpression in 60% and 44% of CRC cases, respectively. Subsequent occurrence of CLM was significantly correlated with the overexpression of LEF1 (chi-square p = 0.035), but not SPP1 (p = 0.14). Kaplan Meier analysis revealed significantly worse survival in patients with overexpression of LEF1 (p < 0.01), but not SPP1 (p = 0.11). Both univariate and multivariate analyses identified stage (p < 0.0001) and LEF1 overexpression (p < 0.05) as important prognostic markers, but not tumor grade or SPP1. CONCLUSION: Among signature genes differentially expressed between CLM and primary CRC, we demonstrate overexpression of LEF1 in primary CRC to be a prognostic factor for poor survival and increased risk for liver metastasis. cDNA microarrays from the Stanford Functional Genomics Facility were used to perform mRNA transcript profiling of 31 freshly-frozen primary colorectal cancer specimens, and compared to published profiles of 32 unmatched colorectal liver metastases and 12 normal liver specimens.