Colorectal cancer gene expression profiling using nanostring nCounter analysis.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 3555-3555
Author(s):  
Kristen Keon Ciombor ◽  
Natasha G Deane ◽  
Keeli B Lewis ◽  
Xi Chen ◽  
Bing Zhang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Colorectal Cancer ◽  
Cell Biology ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Outcome Data ◽  
Rank Test ◽  
Tissue Samples ◽  
Mesenchymal Transition ◽  
E Cadherin

3555 Background: A more accurate method of identifying stage 2 and 3 colorectal cancer (CRC) patients at highest risk for recurrence after surgical resection is needed. Gene expression signatures utilizing microarray-derived gene expression data from fresh frozen primary CRCs to predict risk of recurrence have been developed by us and others. Advances in technology platforms for gene expression measurements and their applicability to formalin-fixed, paraffin-embedded (FFPE) specimens offer new opportunity to develop clinically useful diagnostics based on molecular profiles. Methods: 58 patient FFPE samples of all stages stored from 1-12 years were collected from the Vanderbilt GI SPORE Translational Pathology and Imaging Core and annotated with appropriate clinicopathologic data. 414 genes were selected from our 34-gene prognostic classifier and other published CRC gene signatures, as well as gene elements associated with intestinal stem cell biology and epithelial-to-mesenchymal transition (EMT). RNA was extracted from the tumors, and gene expression analysis was completed using the nCounterplatform. Results: Quality of extracted RNA from tumor blocks was similar among the tumors and adequate for analysis. No significant differences were seen in signal strength (p=0.94, Kruskal-Wallis test) or intra-class variation (correlation coefficient = 0.99) across material extracted from new and old blocks. Fold change values for the 70 most highly differentially expressed genes on the nCounter platform correlated well with Affymetrix U133 plus 2 microarray (R2=0.819). Genes associated with EMT clustered according to prognosis, with poorer prognoses seen in patients with high TWIST expression or low E-cadherin and SMAD4 expression. There was a trend toward better survival outcomes with high expression of E-cadherin and SMAD4 (p=0.072, log-rank test). Conclusions: This preliminary study demonstrates the feasibility of this approach to determine gene expression patterns in FFPE tumor tissue samples. Our data suggest that this approach may be applied to identify clinically applicable prognostic gene expression profiles that may be validated in archived patient samples that are well annotated with patient outcome data.

Identification and validation of gene expression subtypes in a large set of colorectal cancer samples.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 3511-3511 ◽  
Author(s):  
Eva Budinska ◽  
Vlad Calin Popovici ◽  
Katarzyna Otylia Sikora ◽  
Nicolas Lapique ◽  
Sabine Tejpar ◽  
...  
Keyword(s):  
Gene Expression ◽  
Colorectal Cancer ◽  
Molecular Markers ◽  
Molecular Mechanisms ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Stage Ii ◽  
Large Set ◽  
Molecular Processes ◽  
Mesenchymal Transition

3511 Background: From a clinical perspective colorectal cancer (CRC) is a heterogeneous disease whose biological background is insufficiently understood. In order to adapt targeted treatment to biologically different categories of CRC patients, in depth understanding of the molecular mechanisms involved in CRC heterogeneity is urgently needed. Methods: Consensus cluster analysis of 1113 stage II-III CRC gene expression profiles from PETACC3 and 4 public datasets defined a set of subtypes which were confirmed in an independent set of 720 samples. The similarity between tumors was based on a set of 54 meta-genes. This approach improves the robustness to measurement noise and gives equal chances to each biological process to be accounted for in the subtype definition. We tested the association of the subtypes with clinical variables, molecular markers and patient survival. Results: We identified and validated 5 major subtypes A-E, with different levels of expression in 6 main molecular processes: epithelial-mesenchymal transition (EMT), immune response, colon crypt differentiation, proliferation, Wnt signaling and chromosome 20q. Significant differences in survival and an enrichment for markers such as MSI, BRAF mutation, site or p53 status were found between the subtypes. In addition, the new subtype classification uncovered heterogeneity within groups defined by these commonly used markers. Survival analysis showed significant prognostic value for meta-genes connected to EMT, proliferation and differentiation. Identical data processing and clustering applied to the validation set on the same meta-genes resulted in subtypes with almost identical expression patterns. Conclusions: We identified and validated robust molecular subtypes in the largest set of stage II-III CRC samples as a combination of multiple molecular processes, that complement current disease stratification based on clinico-pathological variables and molecular markers. The biological relevance of these subtypes was reflected in significant differences in survival. These insights open new perspectives for improving prognostic models and rationalize the prediction of tumor-specific drug sensitivity.

scholarly journals Transcriptome Profiling of Adipose Tissue Reveals Depot-Specific Metabolic Alterations Among Patients with Colorectal Cancer

2019 ◽  
Vol 104 (11) ◽  
pp. 5225-5237 ◽  
Author(s):  
Mariam Haffa ◽  
Andreana N Holowatyj ◽  
Mario Kratz ◽  
Reka Toth ◽  
Axel Benner ◽  
...  
Keyword(s):  
Gene Expression ◽  
Colorectal Cancer ◽  
Adipose Tissue ◽  
Large Scale ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Human Study ◽  
Subcutaneous Fat ◽  
Specific Gene ◽  
Adipose Tissue Depots

Abstract Context Adipose tissue inflammation and dysregulated energy homeostasis are key mechanisms linking obesity and cancer. Distinct adipose tissue depots strongly differ in their metabolic profiles; however, comprehensive studies of depot-specific perturbations among patients with cancer are lacking. Objective We compared transcriptome profiles of visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) from patients with colorectal cancer and assessed the associations of different anthropometric measures with depot-specific gene expression. Design Whole transcriptomes of VAT and SAT were measured in 233 patients from the ColoCare Study, and visceral and subcutaneous fat area were quantified via CT. Results VAT compared with SAT showed elevated gene expression of cytokines, cell adhesion molecules, and key regulators of metabolic homeostasis. Increased fat area was associated with downregulated lipid and small molecule metabolism and upregulated inflammatory pathways in both compartments. Comparing these patterns between depots proved specific and more pronounced gene expression alterations in SAT and identified unique associations of integrins and lipid metabolism–related enzymes. VAT gene expression patterns that were associated with visceral fat area poorly overlapped with patterns associated with self-reported body mass index (BMI). However, subcutaneous fat area and BMI showed similar associations with SAT gene expression. Conclusions This large-scale human study demonstrates pronounced disparities between distinct adipose tissue depots and reveals that BMI poorly correlates with fat mass–associated changes in VAT. Taken together, these results provide crucial evidence for the necessity to differentiate between distinct adipose tissue depots for a correct characterization of gene expression profiles that may affect metabolic health of patients with colorectal cancer.

scholarly journals Squalene Epoxidase Correlates E-Cadherin Expression and Overall Survival in Colorectal Cancer Patients: The Impact on Prognosis and Correlation to Clinicopathologic Features

2019 ◽  
Vol 8 (5) ◽  
pp. 632 ◽  
Author(s):  
Joo Heon Kim ◽  
Chang Nam Kim ◽  
Dong Wook Kang
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Regional Lymph Node ◽  
Expression Patterns ◽  
Squalene Epoxidase ◽  
Poor Overall Survival ◽  
Aberrant Expression ◽  
Mesenchymal Transition ◽  
The Impact ◽  
E Cadherin

Squalene epoxidase (SE), coded by SQLE, is an important rate-limiting enzyme in the cholesterol biosynthetic pathway. Recently, the aberrant expression of SQLE, which is responsible for epithelial to mesenchymal transition (EMT), has been reported in various types of cancer. This study was undertaken to clarify the clinicopathologic implications of SE in patients with stage I to IV colorectal cancer (CRC). We also analyzed the expression patterns of SE in association with E-cadherin in a series of CRCs. We detected the cytoplasmic expression of SE in 59.4% of carcinoma samples by immunohistochemistry (IHC). There was a significant correlation between a high level of SE expression and lymphovascular (LV) invasion (p < 0.001), tumor budding (p < 0.001), invasion depth (p = 0.002), regional lymph node metastasis (p < 0.001), and pathologic TNM stage (p < 0.001). SE is more abundantly expressed at the invasive front, and reversely correlated with E-cadherin expression. Patients with SE-positive CRC had shorter recurrence-free survival (RFS) and poor overall survival (OS) than those with SE-negative CRC in multivariate analysis (p < 0.001 and p < 0.001, respectively). These data suggest that SE can serve as a valuable biomarker for unfavorable prognosis, and as a possible therapeutic target in CRCs.

scholarly journals P13.10 Glioblastoma within the subventricular zone associates with increased mesenchymal transition: an intratumoral gene expression analysis

2019 ◽  
Vol 21 (Supplement_3) ◽  
pp. iii64-iii64
Author(s):  
S Berendsen ◽  
D Dalemans ◽  
K Draaisma ◽  
P A Robe ◽  
T J Snijders
Keyword(s):  
Gene Expression ◽  
Subventricular Zone ◽  
Epithelial Mesenchymal Transition ◽  
Expression Patterns ◽  
Sequencing Data ◽  
Gene Set Enrichment ◽  
En Bloc ◽  
Tissue Samples ◽  
Mesenchymal Transition ◽  
Gene Set

Abstract BACKGROUND Involvement of the subventricular zone (SVZ) in GBM is associated with poor prognosis and suggested to associate with specific tumor-biological characteristics. The SVZ microenvironment can influence gene expression and migration in GBM cells in preclinical models. We aimed to investigate whether the SVZ microenvironment has any influence on intratumoral gene expression patterns in GBM patients. MATERIAL AND METHODS The publicly available Ivy GBM database contains clinical, radiological and whole exome sequencing data from multiple regions from en bloc resected GBMs. SVZ involvement of the various tissue samples was evaluated on MRI scans. In the tumors that contacted the SVZ, we performed gene expression analyses and gene set enrichment analyses to compare gene (set) expression in tumor regions within the SVZ to tumor regions outside the SVZ, within the same tumors. We also compared these samples to GBMs that made no contact with the SVZ. RESULTS Within GBMs that contacted the SVZ, tissue samples within the SVZ showed enrichment of gene sets involved in (epithelial-)mesenchymal transition, NF-κB and STAT3 signaling, angiogenesis and hypoxia, compared to the samples outside of the SVZ region from the same tumors (p<0.05, FDR<0.25). Comparison of GBM samples within the SVZ region to samples from tumors that did not contact the SVZ yielded similar results. In contrast, we observed no difference in gene set enrichment when comparing the samples outside of the SVZ from SVZ-contacting GBMs with samples from GBMs that did not contact the SVZ at all. CONCLUSION GBM samples in the SVZ region associate with increased (epithelial-)mesenchymal transition and angiogenesis/hypoxia signaling, possibly mediated by the SVZ microenvironment.

scholarly journals Elevated miRNA Inversely Correlates with E-cadherin Gene Expression in Tissue Biopsies from Crohn Disease Patients in contrast to Ulcerative Colitis Patients

2020 ◽  
Vol 2020 ◽  
pp. 1-7
Author(s):  
Małgorzata Guz ◽  
Tomasz Dworzański ◽  
Witold Jeleniewicz ◽  
Marek Cybulski ◽  
Joanna Kozicka ◽  
...  
Keyword(s):  
Gene Expression ◽  
Ulcerative Colitis ◽  
Crohn Disease ◽  
Normal Tissue ◽  
Normal Mucosa ◽  
Normal Colonic Mucosa ◽  
Adjacent Normal Tissue ◽  
Tissue Samples ◽  
Mesenchymal Transition ◽  
E Cadherin

Inflammatory bowel disease (IBD) comprises ulcerative colitis (UC) and Crohn disease (CD). Similar symptoms, but different treatment procedures for both diseases require precise diagnosis. MicroRNAs (miRNAs) are major posttranscriptional players that regulate the expression of genes during the inflammation and thus could be appropriate biomarkers for differentiation between UC and CD. For this purpose, we analyzed the expression of miR-21-3p, miR-31-3p, miR-125b-1-3p, miR-146a-3p, miR-155-5p, and E-cadherin (CDH1) genes associated with IBD, in 67 tissue samples: 28 inflamed mucosa samples (n=16 UC, n=12 CD), 28 adjacent normal colonic mucosa (n=16 UC, n=12 CD), and 11 normal mucosa from healthy patients using reverse transcription real-time RT-PCR. We found all analyzed miRNAs were significantly overexpressed in UC tissue as compared to adjacent normal tissue of patients with UC, as well as to normal mucosa from healthy controls. Four miRNAs (except miR-125b-1-3p) were significantly upregulated in CD lesions as compared to adjacent normal tissue of patients with CD, and four miRNAs, except miR-146a-3p, were significantly higher in CD samples compared to normal mucosa from healthy individuals. In the CD group, we found an inverse correlation between miR-155-5p or miR-146a-3p expressions and CDH1expression in inflamed mucosa. This type of correlation was also detected for miR-213p in adjacent normal tissue and CDH1 in inflamed mucosa, as well as between miR-155-5p and CDH1 in adjacent normal tissue. Elevated miRNA expression is characteristic for IBD-mediated inflammation process and inversely correlated with CDH1 gene expression, which suggest involvement of epithelial to mesenchymal transition (EMT) in IBD development.

TIMP-1 Expression in Human Colorectal Cancer Is Associated with SMAD3 Gene Expression Levels: A Pilot Study

2014 ◽  
Vol 23 (4) ◽  
pp. 413-418 ◽  
Author(s):  
Calin Ionescu ◽  
Cornelia Braicu ◽  
Roxana Chiorean ◽  
Roxana Cojocneanu Petric ◽  
Emilian Neagoe ◽  
...  
Keyword(s):  
Gene Expression ◽  
Colorectal Cancer ◽  
Tumor Tissue ◽  
Transforming Growth Factor ◽  
Prognostic Significance ◽  
Cancer Tissue ◽  
Mesenchymal Transition ◽  
Expression Levels ◽  
Qrt Pcr ◽  
E Cadherin

Background & Aims: The prognosis of colorectal cancer (CRC) varies considerably, and there is a compelling need to identify novel biomarkers with prognostic significance. The aim of the present study was to evaluate the prognostic value of a panel of six genes (CDH1, SMAD3, TGFβ1, ICAM-1, TIMP-1 and MUC12) in CRC patients.Methods. We evaluated these genes by qRT-PCR in normal and CRC tumor tissue, and correlated the relative gene expression values with clinical, pathological aspects and other biological factors.Results. RNA expression levels of CDH1, SMAD3, TGFβ1, ICAM-1, TIMP-1 and MUC12 were measured by qRT-PCR in a set of 39 tumor samples and non-cancer tissue. Statistically significant increases in expression levels were found for ICAM-1 and TIMP-1 when comparing tumor samples to the non-tumor group.Conclusions. Among the genes which displayed differential expressions between tumor tissue and adjoining normal tissue, the ones that presented statistically significant correlations were TIMP-1 and SMAD3, possibly with prognostic significance.Abbreviations: CDH1: E-cadherin; CRC: colorectal cancer; E-cadherin: CDH1; EMT: epithelial-mesenchymal transition; IBD: inflammatory bowel disease; ICAM-1: Intercellular Adhesion Molecule 1; MMPs: matrix metalloproteinases; MUC12: Mucin 12, Cell Surface Associated; OS: overall survival; SMAD3: SMAD Family Member; TGFß1: Transforming growth factor beta 1; TIMP-1: tissue inhibitor of metalloproteinase-1.

scholarly journals Glioblastomas within the Subventricular Zone Are Region-Specific Enriched for Mesenchymal Transition Markers: An Intratumoral Gene Expression Analysis

Cancers ◽  
2021 ◽  
Vol 13 (15) ◽  
pp. 3764
Author(s):  
Diana J. Z. Dalemans ◽  
Sharon Berendsen ◽  
Kaspar Draaisma ◽  
Pierre A. Robe ◽  
Tom J. Snijders
Keyword(s):  
Gene Expression ◽  
Subventricular Zone ◽  
Epithelial Mesenchymal Transition ◽  
Expression Patterns ◽  
Sequencing Data ◽  
Tissue Samples ◽  
Mesenchymal Transition ◽  
Gene Set ◽  
Multiple Regions ◽  
Mri Scans

Background: Involvement of the subventricular zone (SVZ) in glioblastoma is associated with poor prognosis and is associated with specific tumor-biological characteristics. The SVZ microenvironment can influence gene expression in glioblastoma cells in preclinical models. We aimed to investigate whether the SVZ microenvironment has any influence on intratumoral gene expression patterns in glioblastoma patients. Methods: The publicly available Ivy Glioblastoma database contains clinical, radiological and whole exome sequencing data from multiple regions from resected glioblastomas. SVZ involvement of the various tissue samples was evaluated on MRI scans. In tumors that contacted the SVZ, we performed gene expression analyses and gene set enrichment analyses to compare gene (set) expression in tumor regions within the SVZ to tumor regions outside the SVZ. We also compared these samples to glioblastomas that did not contact the SVZ. Results: Within glioblastomas that contacted the SVZ, tissue samples within the SVZ showed enrichment of gene sets involved in (epithelial-)mesenchymal transition, NF-κB and STAT3 signaling, angiogenesis and hypoxia, compared to the samples outside of the SVZ region from the same tumors (p < 0.05, FDR < 0.25). Comparison of glioblastoma samples within the SVZ region to samples from tumors that did not contact the SVZ yielded similar results. In contrast, we observed no differences when comparing the samples outside of the SVZ from SVZ-contacting glioblastomas with samples from glioblastomas that did not contact the SVZ at all. Conclusion: Glioblastoma samples in the SVZ region are enriched for increased (epithelial-)mesenchymal transition and angiogenesis/hypoxia signaling, possibly mediated by the SVZ microenvironment.

scholarly journals Association of MALAT1 and PVT1 Variants, Expression Profiles and Target miRNA-101 and miRNA-186 with Colorectal Cancer: Correlation with Epithelial-Mesenchymal Transition

2021 ◽  
Vol 22 (11) ◽  
pp. 6147
Author(s):  
Abdullah F. Radwan ◽  
Olfat G. Shaker ◽  
Noha A. El-Boghdady ◽  
Mahmoud A. Senousy
Keyword(s):  
Colorectal Cancer ◽  
Lymph Node ◽  
Epithelial Mesenchymal Transition ◽  
Expression Profiles ◽  
Tumor Stage ◽  
Lymph Node Status ◽  
Mesenchymal Transition ◽  
Logistic Analysis ◽  
Diagnostic Potential ◽  
E Cadherin

The influence of PVT1 and MALAT1 variants on colorectal cancer (CRC) susceptibility and their impact on PVT1/miRNA-186/epithelial-mesenchymal transition (EMT) and MALAT1/miRNA-101/EMT axes in CRC are unknown. We investigated the influence of PVT1 rs13255292 and MALAT1 rs3200401 on the risk of CRC and adenomatous polyps (AP), their impact on the long noncoding RNAs PVT1 and MALAT1 expression and their target miRNA-186, miRNA-101/E-cadherin pathways, along with their potential as early CRC biomarkers. Overall, 280 individuals were recruited: 140 patients with CRC, 40 patients with AP, and 100 healthy volunteers. Genotyping and serum expression profiles were assessed using qPCR. The EMT biomarker, E-cadherin, was measured by ELISA. rs3200401 was associated with increased CRC risk, whereas rs13255292 was protective. Serum PVT1 and MALAT1 were upregulated in CRC and AP patients versus healthy controls, whereas, miRNA-186, miRNA-101 and E-cadherin were downregulated in CRC versus non-CRC groups. MALAT1 showed superior diagnostic potential for CRC and predicted CRC risk among non-CRC groups in the multivariate logistic analysis. PVT1, MALAT1, miRNA-186 and miRNA-101 levels were correlated with E-cadherin, tumor stage, lymph node and distant metastasis. E-cadherin was lost in metastatic vs. non-metastatic CRC. rs3200401CC genotype carriers showed higher E-cadherin levels than CC + CT carriers. rs3200401 was correlated with lymph node status. For the first time, rs13255292 and rs3200401 are potential genetic CRC predisposition markers, with rs3200401 possibly impacting the EMT process. Serum PVT1, MALAT1, miRNA-186 and miRNA-101 are novel non-invasive diagnostic biomarkers that could improve the clinical outcome of CRC.

scholarly journals Testing the Gene Expression Classification of the EMT Spectrum

2018 ◽  
Author(s):  
Dongya Jia ◽  
Jason T. George ◽  
Satyendra C. Tripathi ◽  
Deepali L. Kundnani ◽  
Mingyang Lu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Expression Data ◽  
Regulatory Network ◽  
Cancer Metastasis ◽  
Epithelial Mesenchymal Transition ◽  
Expression Profiles ◽  
Expression Patterns ◽  
M Cells ◽  
Expression Data ◽  
Mesenchymal Transition

AbstractThe epithelial-mesenchymal transition (EMT) plays a central role in cancer metastasis and drug resistance – two persistent clinical challenges. Epithelial cells can undergo a partial or full EMT, attaining either a hybrid epithelial/mesenchymal (E/M) or mesenchymal phenotype, respectively. Recent studies have emphasized that hybrid E/M cells may be more aggressive than their mesenchymal counterparts. However, mechanisms driving hybrid E/M phenotypes remain largely elusive. Here, to better characterize the hybrid E/M phenotype(s) and tumor aggressiveness, we integrate two computational methods – (a) RACIPE – to identify the robust gene expression patterns emerging from the dynamics of a given gene regulatory network, and (b) EMT scoring metric - to calculate the probability that a given gene expression profile displays a hybrid E/M phenotype. We apply the EMT scoring metric to RACIPE-generated gene expression data generated from a core EMT regulatory network and classify the gene expression profiles into relevant categories (epithelial, hybrid E/M, mesenchymal). This categorization is broadly consistent with hierarchical clustering readouts of RACIPE-generated gene expression data. We show that the EMT scoring metric can be used to distinguish between samples composed of exclusively hybrid E/M cells and those containing mixtures of epithelial and mesenchymal subpopulations using the RACIPE-generated gene expression data.

scholarly journals Development of a Prognostic Model for Colorectal Cancer Based on Four EMT-related Genes

2020 ◽  
Author(s):  
Shuoyang Hung ◽  
Chao Yang ◽  
Fengyu Cao ◽  
Xiaobo He ◽  
Yongbin Zheng
Keyword(s):  
Gene Expression ◽  
Colorectal Cancer ◽  
Immune Cells ◽  
Subgroup Analysis ◽  
Expression Profiles ◽  
Predictive Ability ◽  
Disease Stage ◽  
Clinicopathological Parameters ◽  
Clinical Parameters ◽  
Mesenchymal Transition

Abstract Background: Epithelial-to-mesenchymal transition (EMT) greatly affects the progression and metastasis of colorectal cancer (CRC) which is one of the most malignant tumors. The goal of this study was to evaluate the prognostic value of EMT-related genes and develop a prognostic nomogram for patients’ overall survival (OS) with CRC. Methods: This retrospective study analyzed gene expression profiles and clinical data in 1099 samples of CRC patients from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Risk signature based on public databases was created and examined for its predictive value in CRC patients. The independence and correlation of risk signature with clinicopathological parameters were respectively evaluated through univariate/multivariate analysis and subgroup analysis. A nomogram was established according to risk signature and clinical parameters and validated for its predictive ability. The correlation of risk signature and infiltrating immune cells in CRC was assessed.Results: A four EMT-related genes (ERGs) based signature was constructed and validated for its ability in prognostic prediction in CRC patients. The results showed the ERGs signature as an independent prognostic factor regarding different clinicopathological parameters including age, gender and clinical stage. Besides, the ERGs signature also performed well in subgroup analysis with T3-T4, N-, M0 and early disease stage. A nomogram based on the ERGs signature combining clinical parameters was constructed which showed a promising predictive ability in prognosis of CRC patients’ OS. In addition, we found a positive correlation of the ERGs signature with six different types of immune cells.Conclusion: A novel ERGs signature was identified in this study and ERGs signature can be useful in predicting the prognosis of CRC patients.

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