scholarly journals FXYD3: A Promising Biomarker for Urothelial Carcinoma

2011 ◽  
Vol 6 ◽  
pp. BMI.S6487 ◽  
Author(s):  
ZhongFa Zhang ◽  
See-Tong Pang ◽  
Katherine A. Kasper ◽  
Chunyan Luan ◽  
Bill Wondergem ◽  
...  
Keyword(s):  
Gene Expression ◽  
Differential Diagnosis ◽  
Urothelial Carcinoma ◽  
Gene Expression Profiling ◽  
Expression Profiling ◽  
Low Grade ◽  
Mrna Levels ◽  
Kidney Tumor ◽  
Normal Kidney ◽  
Tumor Subtypes

Objective Urothelial carcinoma (UC) of the kidney is a relatively rare but aggressive form of kidney cancer. Differential diagnosis of renal UC from renal cell carcinoma (RCC) can be difficult, but is critical for correct patient management. We aimed to use global gene expression profiling to identify genes specifically expressed in urothelial carcinoma (UC) of the kidney, with purpose of finding new biomarkers for differential diagnosis of UC of both upper and lower tract from normal tissues. Materials and Methods Microarray gene expression profiling was performed on a variety of human kidney tumor samples, including clear cell, papillary, chromophobe, oncocytoma, renal UC and normal kidney controls. Differentially expressed mRNAs in various kidney tumor subtypes were thus identified. Protein expression in human UC tumor samples from both upper and lower urinary tract was evaluated by immunohistochemistry. Results FXYD3 (MAT-8) mRNA was specifically expressed in UC of the kidney and not in normal kidney tissue or in any RCC tumor subtypes. FXYD3 mRNA levels displayed equal or better prediction rate for the detection of renal UC than the mRNA levels of selected known UC markers as p63, vimentin, S100P, KRT20 and KRT7. Finally, immunohistochemical staining of clinical UC samples showed that FXYD3 protein is overexpressed in majority of UC of the upper genitourinary tract (encompassing the kidney, ~90%) and in majority of high grade bladder UC (~84%, it's < 40% in low grade tumors, P < 0.001) compared to normal kidney and bladder tissues. Conclusion FXYD3 may be a promising novel biomarker for the differential diagnosis of renal UC and a promising prognosis marker of UC from bladder. Because it was identified genome-widely, FXYD3 may have important biological ramifications for the genetic study of UC.

scholarly journals Identification of cell-of-origin breast tumor subtypes in inflammatory breast cancer by gene expression profiling

2005 ◽  
Vol 95 (3) ◽  
pp. 243-255 ◽  
Author(s):  
Steven J. Van Laere ◽  
Gert G. Van den Eynden ◽  
Ilse Van der Auwera ◽  
Melanie Vandenberghe ◽  
Peter van Dam ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Gene Expression Profiling ◽  
Inflammatory Breast Cancer ◽  
Expression Profiling ◽  
Breast Tumor ◽  
Cell Of Origin ◽  
Tumor Subtypes

scholarly journals Integrated Genomic and Gene Expression Profiling Identifies Two Major Genomic Circuits in Urothelial Carcinoma

PLoS ONE ◽  
2012 ◽  
Vol 7 (6) ◽  
pp. e38863 ◽  
Author(s):  
David Lindgren ◽  
Gottfrid Sjödahl ◽  
Martin Lauss ◽  
Johan Staaf ◽  
Gunilla Chebil ◽  
...  
Keyword(s):  
Gene Expression ◽  
Urothelial Carcinoma ◽  
Gene Expression Profiling ◽  
Expression Profiling

Identification of Genes Which Play a Crucial Role in C/EBPβ Downstream Signalling in ALK+ ALCL Cell Lines.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1943-1943
Author(s):  
Irina Bonzheim ◽  
Martin Irmler ◽  
Natasa Anastasov ◽  
Margit Klier-Richter ◽  
Sabine Schaefer ◽  
...  
Keyword(s):  
Gene Expression ◽  
Western Blot ◽  
Gene Expression Profiling ◽  
Cell Lines ◽  
Pathway Analysis ◽  
Expression Profiling ◽  
Cellular Proliferation ◽  
Compensatory Mechanism ◽  
Mrna Levels ◽  
Qrt Pcr

Abstract Abstract 1943 Poster Board I-966 Introduction: ALK+ anaplastic large cell lymphomas (ALCL) overexpress C/EBPβ, as a consequence of NPM-ALK kinase activity. We recently reported C/EBPβ as a transcription regulator of NPM-ALK induced cellular proliferation. To identify the downstream targets of C/EBPβ that might be responsible for cell proliferation and survival, we performed gene expression profiling and pathway analyses after C/EBPβ gene silencing Materials and Methods: C/EBPβ knockdown was done by lentiviral shRNA-transduction into two ALK+ ALCL cell lines with strong C/EBPβ expression – SUDHL1 and KiJK. At day three after infection, RNA was extracted and used for Gene Chip expression analysis (U133 Plus 2.0 arrays/ Affymetrix). Genes regulated in both cell lines were applied to Genomatix Bibliosphere Pathway analysis. Candidate genes were either strongly influenced by C/EBPβ knockdown, or had promoter binding sites for C/EBPβ, or showed remarkable pathway connections. The influence of C/EBPβ on these genes was validated by qRT-PCR and in part by Western blot. Results: Gene expression profiling analysis resulted in 167 genes being regulated in both cell lines, of which 26 genes were chosen for further analysis. Validation by qRT-PCR confirmed 23/26 genes. Pathway analysis revealed c-Jun, which is a member of the dimeric transcription factor AP-1, as a regulator of C/EBPβ expression. Silencing C/EBPβ led to a clear up-regulation of c-Jun mRNA. Western blot analysis demonstrated that C/EBPβ influenced not only the expression of c-Jun but also its phosphorylation on Ser63 and Ser73. In contrast to what has been reported, we found very low levels of c-Jun expression in ALK+ALCL cells lines and its expression correlated inversely with C/EBPβ mRNA levels. Although it has been shown that c-Jun regulates C/EBPβ expression directly, in ALK+ALCL the expression of C/EBPβ is clearly independent of c-Jun. Our data suggest that c-Jun up-regulation after C/EBPβ knockdown is a compensatory mechanism to maintain C/EBPβ expression. Additionally, of the 26 selected genes, Bibliosphere Analysis identified 12 genes, which might be transcriptionally regulated by C/EBPβ and are primary targets in C/EBPβ downstream signalling. Two of these genes are of particular interest. The anti-apoptotic protein BCL2A1 contains a promoter-binding site for C/EBPβ and has been shown previously to be both strongly regulated in ALK+ALCL and absolutely necessary for its transformation. The second is a DEAD box nucleolar RNA helicase protein involved in ribosomal RNA production and proliferation which we found to be strongly expressed in ALK+ALCL cell lines and primary cases. Conclusions: C/EBPβ silencing in ALK+ALCL cell lines showed 1) an inverse correlation between c-Jun and C/EBPβ mRNA expression levels, 2) the expression of C/EBPβ in ALK+ALCL is independent of c-Jun, 3) genes transcriptionally regulated by C/EBPβ seem to be essential for proliferation and survival in ALK+ALCL. Disclosures: No relevant conflicts of interest to declare.

Gene expression profiling of T-cell inflammation in small cell lung cancer.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e20097-e20097
Author(s):  
Gareth Rivalland ◽  
Ulf Schmitz ◽  
Ramyar Molania ◽  
Chuck Bailey ◽  
Gavin Michael Wright ◽  
...  
Keyword(s):  
Gene Expression ◽  
T Cell ◽  
Gene Expression Profiling ◽  
Expression Profiling ◽  
Checkpoint Inhibitors ◽  
Pearson Correlation ◽  
Tumour Microenvironment ◽  
Immune Checkpoints ◽  
Significant Heterogeneity ◽  
Mrna Levels

e20097 Background: Recent success with the use of checkpoint inhibition in SCLC has increased the importance of understanding the immunological tumour microenvironment. In many tumours gene expression profiling (GEP) of T-cell inflammation and IFN-gamma is correlated with response to checkpoint inhibitors. We present GEP results in a SCLC cohort and correlation of gene expression with IHC analysis of common checkpoints. Methods: SCLC tissue microarrays from 105 histologically confirmed SCLC specimens were scored for IHC staining of immune checkpoints on tumour and tumour infiltrating lymphocytes (TILs). A subgroup of 30 patients had sufficient tissue for GEP. Nanostring nCounter Pan-cancer immune panel, using the previously described RUVIII normalisation method, was used to examine GEP. A 28-gene IFN-G related signature was examined. Results: Median age 67y (range 53 – 86); male: 16/30 (53%); stage: limited 22/30 (73%), 5/30 (17%) extensive, 3/30 (10%) stage unknown. Significant heterogeneity was observed in gene expression. Pearson correlation co-efficients between IHC analysis and corresponding mRNA of PD-L1, PD-L2, LAG3 and TIM3, on both tumour and TILs, were not statistically significant. Significant positive correlation was found for mRNA levels of HAVCR2 (TIM3) with LAG3 and with PDCD1LG2 (PD-L2). As in the larger cohort, TIL co-expression of PD-L1, PD-L2, TIM3 and LAG3 were all associated with improved survival; med OS 89.3 v 15.7 mo; p < 0.01. The cohort clustered into 4 groups with respect to the IFN-G GEP. The group with the highest level of gene expression (5/30 pts, 16.7%) had numerically improved OS; 89.3 v 21.3 mo, p = 0.23. Conclusions: In this limited cohort, gene expression did not consistently correlate with IHC. Co-ordinated expression of T-cell inflamed/IFN-G immune checkpoints occurred in 16.7% SCLC and was associated with improved survival.

scholarly journals Distinct Gene Expression Profiling after Infection of Immature Human Monocyte-Derived Dendritic Cells by the Attenuated Poxvirus Vectors MVA and NYVAC

2007 ◽  
Vol 81 (16) ◽  
pp. 8707-8721 ◽  
Author(s):  
Susana Guerra ◽  
José Luis Nájera ◽  
José Manuel González ◽  
Luis A. López-Fernández ◽  
Nuria Climent ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dendritic Cells ◽  
Gene Expression Profiling ◽  
Expression Profiling ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Human Monocyte ◽  
Type I ◽  
Mrna Levels ◽  
Antigen Uptake

ABSTRACT Although recombinants based on the attenuated poxvirus vectors MVA and NYVAC are currently in clinical trials, the nature of the genes triggered by these vectors in antigen-presenting cells is poorly characterized. Using microarray technology and various analysis conditions, we compared specific changes in gene expression profiling following MVA and NYVAC infection of immature human monocyte-derived dendritic cells (MDDC). Microarray analysis was performed at 6 h postinfection, since these viruses induced extensive cytopathic effects, rRNA breakdown, and apoptosis at late times postinfection. MVA- and NYVAC-infected MDDC shared upregulation of 195 genes compared to uninfected cells: MVA specifically upregulated 359 genes, and NYVAC upregulated 165 genes. Microarray comparison of NYVAC and MVA infection revealed 544 genes with distinct expression patterns after poxvirus infection and 283 genes specifically upregulated after MVA infection. Both vectors upregulated genes for cytokines, cytokine receptors, chemokines, chemokine receptors, and molecules involved in antigen uptake and processing, including major histocompatibility complex genes. mRNA levels for interleukin 12β (IL-12β), beta interferon, and tumor necrosis factor alpha were higher after MVA infection than after NYVAC infection. The expression profiles of transcription factors such as NF-κB/Rel and STAT were regulated similarly by both viruses; in contrast, OASL, MDA5, and IRIG-I expression increased only during MVA infection. Type I interferon, IL-6, and Toll-like receptor pathways were specifically induced after MVA infection. Following MVA or NYVAC infection in MDDC, we found similarities as well as differences between these virus strains in the expression of cellular genes with immunological function, which should have an impact when these vectors are used as recombinant vaccines.

scholarly journals Comparative gene expression profiling of ADAMs, MMPs, TIMPs, EMMPRIN, EGF-R and VEGFA in low grade meningioma

2016 ◽  
Vol 49 (6) ◽  
pp. 2309-2318 ◽  
Author(s):  
Harcharan K. Rooprai ◽  
Andrew J. Martin ◽  
Andrew King ◽  
Usha D. Appadu ◽  
Huw Jones ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Expression Profiling ◽  
Expression Profiling ◽  
Low Grade
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