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.

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.

scholarly journals Association between colorectal cancer and Fusobacterium nucleatum and Bacteroides fragilis bacteria in Iranian patients: a preliminary study

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Aref Shariati ◽  
Shabnam Razavi ◽  
Ehsanollah Ghaznavi-Rad ◽  
Behnaz Jahanbin ◽  
Abolfazl Akbari ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Relative Abundance ◽  
Normal Tissue ◽  
Bacteroides Fragilis ◽  
Fusobacterium Nucleatum ◽  
Normal Mucosa ◽  
Clinicopathologic Characteristics ◽  
Tissue Samples ◽  
Adjacent Normal Mucosa ◽  
Iranian Patients

Abstract Background and aim Recent studies have proposed that commensal bacteria might be involved in the development and progression of gastrointestinal disorders such as colorectal cancer (CRC). Therefore, in this study, the relative abundance of Fusobacterium nucleatum, Bacteroides fragilis, Streptococcus bovis/gallolyticus, and Enteropathogenic Escherichia coli (EPEC) in CRC tissues, and their association with clinicopathologic characteristics of CRC was investigated in Iranian patients. Moreover, the role of these bacteria in the CRC-associated mutations including PIK3CA, KRAS, and BRAF was studied. Method To these ends, the noted bacteria were quantified in paired tumors and normal tissue specimens of 30 CRC patients, by TaqMan quantitative Real-Time Polymerase Chain Reaction (qPCR). Next, possible correlations between clinicopathologic factors and mutations in PIK3CA, KRAS, and BRAF genes were analyzed. Results In studied samples, B. fragilis was the most abundant bacteria that was detected in 66 and 60% of paired tumor and normal samples, respectively. Furthermore, 15% of the B. fragilis-positive patients were infected with Enterotoxigenic B. fragilis (ETBF) in both adenocarcinoma and matched adjacent normal samples. F. nucleatum was also identified in 23% of tumors and 13% of adjacent normal tissue samples. Moreover, the relative abundance of these bacteria determined by 2-ΔCT was significantly higher in CRC samples than in adjacent normal mucosa (p < 0.05). On the other hand, our findings indicated that S. gallolyticus and EPEC, compared to adjacent normal mucosa, were not prevalent in CRC tissues. Finally, our results revealed a correlation between F. nucleatum-positive patients and the KRAS mutation (p = 0.02), while analyses did not show any association between bacteria and mutation in PIK3CA and BRAF genes. Conclusion The present study is the first report on the analysis of different bacteria in CRC tissue samples of Iranian patients. Our findings revealed that F. nucleatum and B. fragilis might be linked to CRC. However, any link between gut microbiome dysbiosis and CRC remains unknown.

scholarly journals Expression of EGF receptors in canine prostate with proliferative inflammatory atrophy and carcinoma

2017 ◽  
Vol 47 (12) ◽  
Author(s):  
Mariana Batista Rodrigues Faleiro ◽  
Lorena Cardoso Cintra ◽  
Rosália Santos Amorim Jesuino ◽  
Eugênio Gonçalves de Araújo ◽  
Rafael Malagoli Rocha ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Product ◽  
Normal Tissue ◽  
Prostatic Carcinoma ◽  
Prostatic Tissue ◽  
Egf Receptors ◽  
Tissue Samples ◽  
Proliferative Inflammatory Atrophy ◽  
Erbb2 Mrna

ABSTRACT: Gene expression of ErbB1 and ErbB2, and immunostaining of EGFR (Her1) and Her2 (c-erbB-2) were evaluated in this study to ascertain whether these receptors are involved in the evolution of canine premalignant and malignant prostatic lesions, as proliferative inflammatory atrophy (PIA) and prostatic carcinoma (PC). With regards to the intensity of EGFR immunostaining, there was no difference between normal prostatic tissue and tissues with PIA or PC. In relation to Her2 immunostaining, there were differences between normal prostatic tissue and those with PIA and PC, as also differences between prostates with PIA and PC. There was no correlation between EGFR and Her2 immunostaining. ErbB1 gene product was detected in two normal tissue samples, in one with PIA, and in all samples with PC. ErbB2 mRNA was recorded in two canine samples with PIA, in all with PC, but was not detected in normal prostatic tissue. It was concluded that EGFR and Her2 play roles in canine PIA and PC, suggesting that those receptors may be involved in canine prostatic carcinogenesis.

Gene expression in tumor-adjacent normal tissue is associated with recurrence in patients with rectal cancer treated with adjuvant chemoradiation

2006 ◽  
Vol 16 (8) ◽  
pp. 555-563 ◽  
Author(s):  
Sylke Schneider ◽  
David J. Park ◽  
Dongyun Yang ◽  
Anthony El-Khoueiry ◽  
Andy Sherrod ◽  
...  
Keyword(s):  
Gene Expression ◽  
Rectal Cancer ◽  
Normal Tissue ◽  
Adjacent Normal Tissue ◽  
Adjuvant Chemoradiation

Decline in serum soluble E-cadherin and low baseline matrix metalloproteinase-9 are associated with response to combination celecoxib and erlotinib therapy in advanced non-small cell lung cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 7640-7640
Author(s):  
K. L. Reckamp ◽  
B. K. Gardner ◽  
R. A. Figlin ◽  
D. Elashoff ◽  
K. Krysan ◽  
...  
Keyword(s):  
Gene Expression ◽  
Lung Cancer ◽  
Combination Therapy ◽  
Matrix Metalloproteinase ◽  
Epithelial To Mesenchymal Transition ◽  
Advanced Nsclc ◽  
Mesenchymal Transition ◽  
Best Response ◽  
Cox 2 ◽  
E Cadherin

7640 Background: Cyclooxygenase-2 (COX-2) overexpression may mediate resistance to EGFR TK inhibition through prostaglandin E2 (PGE2)-dependent promotion of epithelial to mesenchymal transition (EMT). Thomson, et al. reported that the suppression of epithelial markers such as E-cadherin led to resistance to erlotinib (Cancer Res 2005;65:9455). In addition, PGE2 downregulates E-cadherin expression by upregulating transcriptional repressors including ZEB1 and Snail, as described by Dohadwala et al (Cancer Res 2006;66:5338). These findings suggest that COX-2 inhibition may enhance the efficacy of EGFR TKI therapy in NSCLC. Methods: A phase I, dose escalation trial to was performed investigating the combination of celecoxib and erlotinib in pts with advanced NSCLC. Soluble E-cadherin (sEC) was evaluated by ELISA in pt serum at baseline and weeks 4 and 8 of treatment. Other markers of COX-2 gene expression were evaluated by ELISA, including matrix metalloproteinase (MMP)-9, MMP-2 and tissue inhibitor of MMP (TIMP1). Results: 22 pts were enrolled and 21 were evaluable for the determination of the optimal dose, toxicity assessment and response (reported in Clin Cancer Res 2006;12:3381). Here we report serum sEC and MMP-9 levels, which were analyzed according to best response (PR, SD or PD) in 21 pts. SEC was analyzed according to best response (PR, SD or PD). We found a significant decrease in sEC between baseline and week 8 in pts with PR when compared to those with SD or PD (p = 0.021). In pts who responded to the combination therapy, baseline MMP-9 was significantly lower compared to non-responders (p = 0.006). Conclusions: SEC, MMP-9 and other downstream markers of COX-2 gene expression may be useful for assessing response to combination celecoxib and erlotinib in pts with advanced NSCLC. A randomized Phase II trial is planned comparing erlotinib and celecoxib with erlotinib plus placebo in advanced NSCLC, to evaluate the efficacy of this combination therapy and to assess these and other biomarkers in both serum and tumor tissue. Supported by ASCO Young Investigator Award, UCLA Lung Cancer SPORE NCI P50 CA 90388 and GLAVAHS Career Development Award. No significant financial relationships to disclose.

scholarly journals Gene expression profiling of CD8+ T cells predicts prognosis in patients with Crohn disease and ulcerative colitis

2011 ◽  
Vol 121 (10) ◽  
pp. 4170-4179 ◽  
Author(s):  
James C. Lee ◽  
Paul A. Lyons ◽  
Eoin F. McKinney ◽  
John M. Sowerby ◽  
Edward J. Carr ◽  
...  
Keyword(s):  
Gene Expression ◽  
Ulcerative Colitis ◽  
T Cells ◽  
Gene Expression Profiling ◽  
Cd8 T Cells ◽  
Crohn Disease ◽  
Expression Profiling

scholarly journals Slug and Vimentin Downregulation at the Metastatic Site Is Associated With Skip-N2 Metastasis of Lung Adenocarcinoma

2022 ◽  
Author(s):  
Yasemin SAYGIDEGER ◽  
Alper AVCI ◽  
Emine BAGIR ◽  
Burcu SAYGIDEĞER DEMİR ◽  
Aycan SEZAN Ms ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Epithelial Mesenchymal Transition ◽  
Survival Rates ◽  
Cancer Tissue ◽  
Mrna Levels ◽  
Bioinformatics Analyses ◽  
Tissue Samples ◽  
Mesenchymal Transition ◽  
Slug Expression ◽  
E Cadherin

Abstract Objective: Lung cancer displays heterogeneity both in the tumor itself and in its metastatic regions. One interesting behavior of the tumor is known as Skip N2 metastasis, which N2 lymph nodes contain tumor cells while N1 are clean. In this study, mRNA levels of epithelial mesenchymal transition (EMT) related genes in skip N2 and normal N2 involvements of non-small cell lung cancer tissues were investigated to evaluate the possible molecular background that may contribute to the pathogenesis of Skip N2 metastasis. Materials and Methods: Eighty-three surgically resected and paraffin embedded lymph node samples of lung cancer patients were analyzed in this study, which 40 of them were Skip N2. N2 tissues were sampled from 50% tumor containing areas and total RNA was extracted. mRNA levels for 18S, E-cadherin, Vimentin, ZEB1 and SLUG were analyzed via qPCR and E-cadherin and vimentin protein levels via immunohistochemistry (IHC). Bioinformatic analysis were adopted using online datasets to evaluate significantly co-expressed genes with SLUG in lung cancer tissue samples.Results: Skip-N2 patients who had adenocarcinoma subtype had better survival rates. Comparative analysis of PCR results indicated that Skip N2 tumor tissues had increased E-Cadherin/Vimentin ratio and ZEB1 mRNA expression, and significantly decreased levels of SLUG. E-cadherin IHC staining were higher in Skip N2 and Vimentin were in Non-Skip N2. TP63 had a strong correlation with SLUG expression in the bioinformatics analyses.Conclusion: The results indicate that, at molecular level, Skip N2 pathogenesis has different molecular background and regulation of SLUG expression may orchestrate the process.

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 DNA methylation markers for diagnosis and prognosis of common cancers

2017 ◽  
Vol 114 (28) ◽  
pp. 7414-7419 ◽  
Author(s):  
Xiaoke Hao ◽  
Huiyan Luo ◽  
Michal Krawczyk ◽  
Wei Wei ◽  
Wenqiu Wang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Dna Methylation ◽  
Cancer Biology ◽  
Normal Tissue ◽  
Diagnostic Methods ◽  
Adjacent Normal Tissue ◽  
Tissue Samples ◽  
Diagnosis And Prognosis ◽  
Cancer Metastases ◽  
Colorectal Cancer Metastases

The ability to identify a specific cancer using minimally invasive biopsy holds great promise for improving the diagnosis, treatment selection, and prediction of prognosis in cancer. Using whole-genome methylation data from The Cancer Genome Atlas (TCGA) and machine learning methods, we evaluated the utility of DNA methylation for differentiating tumor tissue and normal tissue for four common cancers (breast, colon, liver, and lung). We identified cancer markers in a training cohort of 1,619 tumor samples and 173 matched adjacent normal tissue samples. We replicated our findings in a separate TCGA cohort of 791 tumor samples and 93 matched adjacent normal tissue samples, as well as an independent Chinese cohort of 394 tumor samples and 324 matched adjacent normal tissue samples. The DNA methylation analysis could predict cancer versus normal tissue with more than 95% accuracy in these three cohorts, demonstrating accuracy comparable to typical diagnostic methods. This analysis also correctly identified 29 of 30 colorectal cancer metastases to the liver and 32 of 34 colorectal cancer metastases to the lung. We also found that methylation patterns can predict prognosis and survival. We correlated differential methylation of CpG sites predictive of cancer with expression of associated genes known to be important in cancer biology, showing decreased expression with increased methylation, as expected. We verified gene expression profiles in a mouse model of hepatocellular carcinoma. Taken together, these findings demonstrate the utility of methylation biomarkers for the molecular characterization of cancer, with implications for diagnosis and prognosis.

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