scholarly journals Cell polarity and cell adhesion associated gene expression differences between invasive micropapillary and no special type breast carcinomas and their prognostic significance

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Zsófia Kramer ◽  
István Kenessey ◽  
Ambrus Gángó ◽  
Gábor Lendvai ◽  
Janina Kulka ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Adhesion ◽  
Mrna Expression ◽  
Cell Polarity ◽  
Expression Profiles ◽  
Prognostic Significance ◽  
Lymph Node Status ◽  
Invasive Micropapillary Carcinoma ◽  
Breast Carcinomas ◽  
Mesenchymal Transition

AbstractInvasive micropapillary carcinoma of the breast (IMPC) has been in the focus of several studies given its specific histology and clinicopathological course. We analysed mRNA expression profiles and the prognostic value of 43 genes involved in cell polarity, cell-adhesion and epithelial–mesenchymal transition (EMT) in IMPC tumors and compared them to invasive breast carcinomas of no special type (IBC-NST). IMPCs (36 cases), IBC-NSTs (36 cases) and mixed IMPC-IBC NSTs (8 cases) were investigated. mRNA expression level of selected genes were analysed using the NanoString nCounter Analysis System. Distant metastases free survival (DMFS) intervals were determined. Statistical analysis was performed using Statistica 13.5 software. Twelve genes showed significantly different expression in the IMPC group. There was no difference in DMFS according to histological type (IBC-NST vs. IMPC). High CLDN3, PALS1 and low PAR6 expression levels in the entire cohort were associated with shorter DMFS, and PALS1 was proven to be grade independent prognostic factor. Positive lymph node status was associated with higher levels of AKT1 expression. Differences in gene expression in IMPC versus IBC-NST may contribute to the unique histological appearance of IMPCs. No marked differences were observed in DMFS of the two groups. Altered gene expression in the mTOR signaling pathway in both tumor subtypes highlights the potential benefit from AKT/mTOR inhibitors in IMPCs similarly to IBC-NSTs.

scholarly journals Early Response of CD8+ T Cells in COVID-19 Patients

2021 ◽  
Vol 11 (12) ◽  
pp. 1291
Author(s):  
Deni Ramljak ◽  
Martina Vukoja ◽  
Marina Curlin ◽  
Katarina Vukojevic ◽  
Maja Barbaric ◽  
...  
Keyword(s):  
Gene Expression ◽  
Immune Response ◽  
T Cells ◽  
Mrna Expression ◽  
Cd8 T Cells ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Effector Memory ◽  
Healthy Controls ◽  
Ifn Γ

Healthy and controlled immune response in COVID-19 is crucial for mild forms of the disease. Although CD8+ T cells play important role in this response, there is still a lack of studies showing the gene expression profiles in those cells at the beginning of the disease as potential predictors of more severe forms after the first week. We investigated a proportion of different subpopulations of CD8+ T cells and their gene expression patterns for cytotoxic proteins (perforin-1 (PRF1), granulysin (GNLY), granzyme B (GZMB), granzyme A (GZMA), granzyme K (GZMK)), cytokine interferon-γ (IFN-γ), and apoptotic protein Fas ligand (FASL) in CD8+ T cells from peripheral blood in first weeks of SARS-CoV-2 infection. Sixteen COVID-19 patients and nine healthy controls were included. The absolute counts of total lymphocytes (p = 0.007), CD3+ (p = 0.05), and CD8+ T cells (p = 0.01) in COVID-19 patients were significantly decreased compared to healthy controls. In COVID-19 patients in CD8+ T cell compartment, we observed lower frequency effector memory 1 (EM1) (p = 0.06) and effector memory 4 (EM4) (p < 0.001) CD8+ T cells. Higher mRNA expression of PRF1 (p = 0.05) and lower mRNA expression of FASL (p = 0.05) at the fifth day of the disease were found in COVID-19 patients compared to healthy controls. mRNA expression of PRF1 (p < 0.001) and IFN-γ (p < 0.001) was significantly downregulated in the first week of disease in COVID-19 patients who progressed to moderate and severe forms after the first week, compared to patients with mild symptoms during the entire disease course. GZMK (p < 0.01) and FASL (p < 0.01) mRNA expression was downregulated in all COVID-19 patients compared to healthy controls. Our results can lead to a better understanding of the inappropriate immune response of CD8+ T cells in SARS-CoV2 with the faster progression of the disease.

scholarly journals MON-500 Cell Adhesion Molecules mRNA Expression in Thyroid Tumors

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Larissa Teodoro ◽  
Karina Colombera Peres ◽  
Matheus Nascimento ◽  
Elisangela Souza Teixeira ◽  
Icleia Siqueira Barreto ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Adhesion ◽  
Mrna Expression ◽  
Adhesion Molecules ◽  
Cell Adhesion Molecules ◽  
Cancer Biology ◽  
Thyroid Nodules ◽  
Thyroid Tumors ◽  
Papillary Thyroid ◽  
Thyroid Carcinomas

Abstract Thyroid cancer biology is extremely diverse. While some cases never progress clinically or do so indolently, others evolve aggressively and may even lead to death. Cell adhesion molecules are glycoproteins present in the cell membrane and play an important role in inflammatory and neoplastic diseases by recruiting immune cells to these sites. The aim of the present study was to investigate the role of mRNA expression of SELL, ICAM1 and ITGAL in thyroid tumors and their relationship with lymphocyte infiltration. We evaluated by RT-qPCR technique 191 thyroid nodules including 97 benign (79 females, 17 males; 49.8±12.5 years old) and 94 malignant (71 females, 23 males; 48.3±15.5years old) cases. Clinical and pathology data were obtained from 47 goiters; 50 follicular adenomas (FA); 74 papillary thyroid carcinomas (PTC), including: 29 classic papillary thyroid carcinomas (CPTC), 21 follicular variant of PTC (FVPTC), 12oxifilic variant of PTC (OVPTC), 12 tall cell papillary thyroid carcinomas (TCPTC); and 20 follicular thyroid carcinomas (FTC). All patients were managed according to a standard protocol based on current guidelines and followed-up for 78.7±54.2 months. SELL was more expressed in malignant (0.85±1.54 UA) than in benign (0.54±0.71 UA, p=0.0027) nodules. The same occurred with ICAM1 (0.99±1.41 vs. 0.46±0.85, p=0.0001), but not with ITGAL gene expression (1.04±1.63 vs. 0.76±1.21, p=0.2131). In addition, the expression of SELL was different when we compared PTC with FA (0.94±1.62 UA vs. 0.47±0.72 UA, p=0.0018) and FTC with FA (0.82±2.38 UA vs. 0.47±0.72 UA, p=0.0078). ICAM1 expression was lower in goiters (0.46±0.90 UA) when compared with PTC (0.93±1.22 UA, p=0.0030) and FTC (1.03±3.30 UA, p=0.0207). Higher expression of ICAM1 (1.16±3.04 UA vs. 0.52±0.96 UA, p=0.0064) and ITGAL (1.17±1.54 UA vs. 0.49±1.39 UA, p=0.0244) was observed in tumors with lymphocyte infiltrate. Also, ITGAL gene expression was higher in tumors that had distant metastasis at diagnosis (1.53±2.18 UA vs. 0.57±1.10 UA, p=0.0217). We were not able to demonstrate any association between any of the investigated molecules and patients’ outcome. In conclusion, our data suggest that cell adhesion molecules may play an important role in neoplastic thyroid cells proliferation. In addition, our findings show that gene expression of SELL and ICAM1 may assist in the histological characterization of follicular patterned thyroid nodules.

scholarly journals Identification of key biomarkers associated with development and prognosis in patients with ovarian carcinoma: evidence from bioinformatic analysis

2019 ◽  
Vol 12 (1) ◽  
Author(s):  
Jiayu Shen ◽  
Shuqian Yu ◽  
Xiwen Sun ◽  
Meichen Yin ◽  
Jing Fei ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Adhesion ◽  
Adhesion Molecules ◽  
Transforming Growth Factor Beta ◽  
Cell Adhesion Molecules ◽  
Cellular Response ◽  
Transforming Growth Factor ◽  
Expression Profiles ◽  
Regulation Of Transcription ◽  
Hub Genes

Abstract Background Ovarian cancer (OC) is the deadliest cause in the gynecological malignancies. Most OC patients are diagnosed in advanced stages with less than 40% of women cured. However, the possible mechanism underlying tumorigenesis and candidate biomarkers remain to be further elucidated. Results Gene expression profiles of GSE18520, GSE54388, and GSE27651 were available from Gene Expression Omnibus (GEO) database with a total of 91 OC samples and 22 normal ovarian (OV) tissues. Three hundred forty-nine differentially expressed genes (DEGs) were screened between OC tissues and OV tissues via GEO2R and online Venn software, followed by KEGG pathway and gene ontology (GO) enrichment analysis. The enriched functions and pathways of these DEGs contain male gonad development, cellular response to transforming growth factor beta stimulus, positive regulation of transcription from RNA polymerase II promoter, calcium independent cell-cell adhesion via plasma membrane cell adhesion molecules, extracellular matrix organization, pathways in cancer, cell cycle, cell adhesion molecules, PI3K-AKT signaling pathway, and progesterone mediated oocyte maturation. The protein-protein network (PPI) was established and module analysis was carried out using STRING and Cytoscape. Next, with PPI network analyzed by four topological methods in Cytohubba plugin of Cytoscape, 6 overlapping genes (DTL, DLGAP5, KIF15, NUSAP1, RRM2, and TOP2A) were eventually selected. GEPIA and Oncomine were implemented for validating the gene expression and all the six hub genes were highly expressed in OC specimens compared to normal OV tissues. Furthermore, 5 of 6 genes except for DTL were associated with worse prognosis using Kaplan Meier-plotter online tool and 3 of 6 genes were significantly related to clinical stages, including RRM2, DTL, and KIF15. Additionally, cBioPortal showed that TOP2A and RRM2 were the targets of cancer drugs in patients with OC, indicating the other four genes may also be potential drug targets. Conclusion Six hub genes (DTL, DLGAP5, KIF15, NUSAP1, RRM2, and TOP2A) present promising predictive value for the development and prognosis of OC and may be used as candidate targets for diagnosis and treatment of OC.

scholarly journals Silencing of MBD1 and MeCP2 in prostate-cancer-derived PC3 cells produces differential gene expression profiles and cellular phenotypes

2008 ◽  
Vol 28 (6) ◽  
pp. 319-326 ◽  
Author(s):  
Ahmed Yaqinuddin ◽  
Farhat Abbas ◽  
Syed Z. Naqvi ◽  
Mohammad U. Bashir ◽  
Romena Qazi ◽  
...  
Keyword(s):  
Gene Expression ◽  
Prostate Cancer ◽  
Mrna Expression ◽  
Cellular Proliferation ◽  
Expression Profiles ◽  
Boyden Chamber ◽  
Invasion And Migration ◽  
Pc3 Cells ◽  
And Migration

Alterations in genomic CpG methylation patterns have been found to be associated with cell transformation and neoplasia. Although it is recognized that methylation of CpG residues negatively regulates gene expression, how the various MBPs (methyl-binding proteins) contribute to this process remains elusive. To determine whether the two well characterized proteins MeCP2 (methyl-CpG-binding protein 2) and MBD1 (methyl-CpG-binding domain 1) have distinct or redundant functions, we employed RNAi (RNA interference) to silence their expression in the prostate cancer-derived PC3 cell line, and subsequently compared cell growth, invasion and migration properties of these cell lines in addition to their respective mRNA-expression profiles. Cells devoid of MeCP2 proliferated more poorly compared with MBD1-deficient cells and the parental PC3 cells. Enhanced apoptosis was observed in MeCP2-deficient cells, whereas apoptosis in parental and MBD1-deficient cells appeared to be equivalent. Boyden chamber invasion and wound-healing migration assays showed that MBD1-silenced cells were both more invasive and migratory compared with MeCP2-silenced cells. Finally, gene chip microarray analyses showed striking differences in the mRNA-expression profiles obtained from MeCP2- and MBD1-depleted cells relative to each other as well as when compared with control cells. The results of the present study suggest that MeCP2 and MBD1 silencing appear to affect cellular processes independently in vivo and that discrete sets of genes involved in cellular proliferation, apoptosis, invasion and migration are targeted by each protein.

PD.128 Gene expression profiles of oralsquamous cell carcinoma depending on lymph node status

2005 ◽  
Vol 1 (1) ◽  
pp. 104
Author(s):  
T. Fillies ◽  
H. Bürger ◽  
B. Brandt ◽  
D. Kemmmg ◽  
R. Werkmeister ◽  
...  
Keyword(s):  
Gene Expression ◽  
Lymph Node ◽  
Cell Carcinoma ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Lymph Node Status ◽  
Node Status

scholarly journals Prognostic Significance of Gene Expression Profiles of Metastatic Neuroblastomas Lacking MYCN Gene Amplification

2006 ◽  
Vol 98 (17) ◽  
pp. 1193-1203 ◽  
Author(s):  
Shahab Asgharzadeh ◽  
Roger Pique-Regi ◽  
Richard Sposto ◽  
Hong Wang ◽  
Yujun Yang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Amplification ◽  
Expression Profiles ◽  
Prognostic Significance ◽  
Gene Expression Profiles ◽  
Mycn Gene

Genetic control of global gene expression levels in the intestinal mucosa: a human twin study

2009 ◽  
Vol 38 (1) ◽  
pp. 73-79 ◽  
Author(s):  
Robert Häsler ◽  
Alexander Begun ◽  
Sandra Freitag-Wolf ◽  
Martin Kerick ◽  
Nancy Mah ◽  
...  
Keyword(s):  
Gene Expression ◽  
Mrna Expression ◽  
Genetic Control ◽  
Intestinal Mucosa ◽  
Expression Profiles ◽  
Global Gene Expression ◽  
Model Organisms ◽  
Expression Levels ◽  
Molecular Phylogenetic ◽  
Health And Disease

Phenotypic variation between individuals, such as different mRNA expression levels, is influenced by genetic and nongenetic factors. Although several studies have addressed the interplay between genotypes and expression profiles in various model organisms in the recent years, the detailed and relative contributions of genetic and nongenetic factors in regulating plasticity of gene expression in barrier organs (e.g., skin, gut), which are exposed to continuous environmental challenge, are still poorly understood. Here we systematically monitored the level of genetic control over genomewide mRNA expression profiles in the healthy intestinal mucosa of 10 monozygotic and 10 dizygotic human twin pairs with microarray analyses. Our results, which are supported by real-time PCR and analysis of molecular phylogenetic conservation, indicate that genes associated with energy metabolism and cell and tissue regeneration pathways are under strong genetic control. Conversely, genes associated with immune response seem to be mainly controlled by exogenous factors. Further insights into the relative extent of genetic and nongenetic determinants of transcriptomal profiles and their influence on physiological and pathophysiological mechanisms are crucial to understanding the key role played by gene-environment interactions in health and disease.

Prognostic Significance of Multidrug Resistance Gene 1 (MDR1), Multidrug Resistance-Related Protein (MRP) and Lung Resistance Protein (LRP) mRNA Expression in Acute Leukemia.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4418-4418
Author(s):  
Hee Jin Huh ◽  
Chan-Jeoung Park ◽  
Seongsoo Jang ◽  
Eul-Ju Seo ◽  
Hyun-Sook Chi ◽  
...  
Keyword(s):  
Gene Expression ◽  
Multidrug Resistance ◽  
Acute Leukemia ◽  
Mrna Expression ◽  
Prognostic Significance ◽  
Multidrug Resistance Gene ◽  
Lung Resistance Protein ◽  
Mdr1 Mrna ◽  
Resistance Protein ◽  
Multidrug Resistance Related Protein

Abstract The prognostic significance of multidrug resistance (MDR) gene expression is controversial. We investigated whether multidrug resistance gene 1 (MDR1), multidrug resistance-related protein (MRP) and lung resistance protein (LRP) mRNA expression are associated with outcomes in acute leukemia patients. At diagnosis we examined MDR1, MRP and LRP mRNA expression in bone marrow samples from 71 acute leukemia patients (AML 39, ALL 32) using nested reverse transcription polymerase chain reaction (RT-PCR). The expression of each of these genes was then expressed as a ratio in relation to ß-actin gene expression, and the three genes were categorized as being either not expressed (0), weakly expressed (1+), moderately expressed (2+) or strongly expressed (3+). MDR1, MRP and LRP mRNA expression was detected in 23.9%, 83.1% and 45.1%, respectively, of acute leukemia patients. LRP mRNA expression was significantly associated with resistance to induction chemotherapy in acute leukemia patients, and in the AML proportion of these patients, compared to LRP-negative patients (p=0.02 and p=0.03, respectively). MRP and high MDR1 mRNA expression was associated with poorer 2-year survival (P=0.049 and p=0.04, respectively) compared to MRP-negative and non-high MDR1 mRNA-expressing patients, respectively. Patients expressing both MRP and LRP mRNA had poorer outcomes in response to induction chemotherapy and had worse 2-year survival compared to patients not expressing both genes. The present data suggest that MDR gene expression affects CR and survival rates in acute leukemia patients. Thus, determination of MDR gene expression at diagnosis appears likely to provide useful prognostic information for acute leukemia patients.

scholarly journals Dynamic mRNA Expression Analysis of the Secondary Palatal Morphogenesis in Miniature Pigs

2019 ◽  
Vol 20 (17) ◽  
pp. 4284
Author(s):  
Jia Liu ◽  
Jing Chen ◽  
Dong Yuan ◽  
Lindong Sun ◽  
Zhipeng Fan ◽  
...  
Keyword(s):  
Gene Expression ◽  
Mrna Expression ◽  
Cleft Lip ◽  
Integration Site ◽  
Expression Profiles ◽  
Mitogen Activated Protein Kinase ◽  
Large Animal Model ◽  
Large Animal ◽  
Palate Development ◽  
Miniature Pigs

Normal mammalian palatogenesis is a complex process that requires the occurrence of a tightly regulated series of specific and sequentially regulated cellular events. Cleft lip/palate (CLP), the most frequent craniofacial malformation birth defects, may occur if any of these events undergo abnormal interference. Such defects not only affect the patients, but also pose a financial risk for the families. In our recent study, the miniature pig was shown to be a valuable alternative large animal model for exploring human palate development by histology. However, few reports exist in the literature to document gene expression and function during swine palatogenesis. To better understand the genetic regulation of palate development, an mRNA expression profiling analysis was performed on miniature pigs, Sus scrofa. Five key developmental stages of miniature pigs from embryonic days (E) 30–50 were selected for transcriptome sequencing. Gene expression profiles in different palate development stages of miniature pigs were identified. Nine hundred twenty significant differentially expressed genes were identified, and the functional characteristics of these genes were determined by gene ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Some of these genes were associated with HH (hedgehog), WNT (wingless-type mouse mammary tumor virus integration site family), and MAPK (mitogen-activated protein kinase) signaling, etc., which were shown in the literature to affect palate development, while some genes, such as HIP (hedgehog interacting protein), WNT16, MAPK10, and LAMC2 (laminin subunit gamma 2), were additions to the current understanding of palate development. The present study provided a comprehensive analysis for understanding the dynamic gene regulation during palate development and provided potential ideas and resources to further study normal palate development and the etiology of cleft palate.

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