scholarly journals Gene Expression Analysis in Four Dogs With Canine Pemphigus Clinical Subtypes Reveals B Cell Signatures and Immune Activation Pathways Similar to Human Disease

2021 ◽  
Vol 8 ◽  
Author(s):  
Haya S. Raef ◽  
Cesar Piedra-Mora ◽  
Neil B. Wong ◽  
Diana Junyue Ma ◽  
Clement N. David ◽  
...  

Pemphigus is a group of autoimmune-mediated mucocutaneous blistering diseases characterized by acantholysis. Pemphigus has also been recognized in dogs and shares similar clinical characteristics and variants with human pemphigus. While relationships between human and canine pemphigus have been reported, gene expression patterns across species have not been described in the literature. We sought to perform gene expression analysis of lesional skin tissue from four dogs with various forms of pemphigus to examine gene expression during spontaneous disease in dogs. We found increased T and B cell signatures in canine pemphigus lesions compared to controls, as well as significant upregulation of CCL3, CCL4, CXCL10, and CXCL8 (IL8), among other genes. Similar chemokine/cytokine expression patterns and immune infiltrates have been reported in humans, suggesting that these genes play a role in spontaneous disease. Direct comparison of our dataset to previously published human pemphigus datasets revealed five conserved differentially expressed genes: CD19, WIF1, CXCL10, CD86, and S100A12. Our data expands our understanding of pemphigus and facilitates identification of biomarkers for prediction of disease prognosis and treatment response, which may be useful for future veterinary and human clinical trials.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 8575-8575
Author(s):  
Jose Carlos Benitez ◽  
Bastien Job ◽  
Vincent Thomas de Montpreville ◽  
Ludovic Lacroix ◽  
Patrick Saulnier ◽  
...  

8575 Background: TETs are rare malignancies of the anterior mediastinum. Clinical behavior varies from mild thymoma (T) A to aggressive thymic carcinoma (TC). The biology of TETs is poorly understood and knowledge of the transcriptomic fingerprint of T and TC is limited. Additionally, up to 30% of patients (pts) will develop associated autoimmune disorders (AIDs). We aimed to characterize the main cancer activation pathways of the TET subgroups. Methods: We selected a representative balanced set of Ts and TCs to analyze 24 main cancer activation pathways using HTG Oncology biomarkers panel (2562 genes) by RNA sequencing. Tumor representative paraffin-embedded blocks were macrodissected for gene expression analysis. We analyzed epidemiologic, clinical and pathological characteristics of pts with TET’s and correlated with genes expression based on cancer Hallmarks. Results: From January 2010 to December 2019, 219 pts were included in the cohort. Molecular results of 194 pts were available. Median age at diagnosis was 56 (9-83) years. 54.1% were women. 65/194 (33.5%) reported AIDs. T B2 was the most frequent (n=41, 21.1%), followed by B1, AB, B3, TC and A. RNA expression analysis identified 2 main clusters, corresponding mainly to T (cluster 2) and TC (cluster 1) respectively (p<0.0001) (Table). Tumors of cluster 1 (TCs predominant) shown activated pathways (MYC [gene ratio= 0.5]; p<0.0001). In cluster 2 (T predominant), activated pathways differed among subgroups: B1 (E2F[0.5], G2M checkpoint [0.45]; p<0.001), B2 (E2F [>0.4]; p<0.0001). Routes were mostly suppressed: A (MYC [>0.5], E2F[>0.4], G2M checkpoint[>0.45], mitotic spindle[>0.35], MTOR [<0.35]; p<0.001), AB (INFα [>0.5], inflammatory response [>0.45], INTɣ [0.45], NFkb [>0.4], MTOR[>0.4]; p<0.001), B1 (EMT [0.6], angiogenesis [>0.5], INFα [0.5], homeostasis [0.5], NFkb [0.5], INTɣ [>0.45], myogenesis [<0.4]; p<0.0001), B2 (INFα [>0.65], INTɣ [>0.5], NFkb [0.5], EMT [0.45], inflammatory response [<0.4]; p< 0.0001), B3 (EMT [0.6], MYC [0.45]; p<0.001). Among pts reporting AIDs 61 and 4 were associated to cluster 2 and 1, respectively (p=0.017). Conclusions: We describe differential molecular characteristics among histological subgroups in 2 clusters. The analysis suggests new therapeutic venues. Additional analysis will be presented on outliers and response to treatment.[Table: see text]


Oncotarget ◽  
2016 ◽  
Vol 7 (35) ◽  
pp. 56781-56797 ◽  
Author(s):  
Oliver Wood ◽  
Jeongmin Woo ◽  
Gregory Seumois ◽  
Natalia Savelyeva ◽  
Katy J. McCann ◽  
...  

2010 ◽  
Vol 28 (15_suppl) ◽  
pp. e21031-e21031
Author(s):  
J. Laes ◽  
P. Godard ◽  
L. Gatto ◽  
J. Detiffe ◽  
L. Alexandre

2017 ◽  
Vol 2017 ◽  
pp. 1-14 ◽  
Author(s):  
Mbaye Tine

The present work examines the induction of theband 3 anion transport protein,mitogen-activated protein kinase, andlactate dehydrogenase, respectively related to osmolyte transport, cell volume regulation, and energy production in the gills of two tilapia strains exposed to either freshwater or hypersaline water. Overall, genes showed similar expression patterns between strains. However, a wild population survey across a range of natural habitats and salinities did not reveal the expected patterns. Although significant, the correlations between gene expression and salinity were slightly ambiguous and did not show any link with phenotypic differences in life history traits previously reported between the same populations. The differential expression was also not associated with the population genetic structure inferred from neutral markers. The results suggest that the differential expression observed is not the result of evolutionary forces such as genetic drift or adaptation by natural selection. Instead, it can be speculated that genes responded to various abiotic and biotic stressors, including factors intrinsic to animals. This study provides clear evidence of the complexity of gene expression analysis in wild populations and shows that more attention needs to be paid when selecting candidates as potential biomarkers for monitoring adaptive responses to a specific environmental perturbation.


2013 ◽  
Vol 3 (4) ◽  
pp. 60-72 ◽  
Author(s):  
Gerald Schaefer ◽  
Tomoharu Nakashima

Microarray studies and gene expression analysis have received a lot of attention and provide many promising avenues towards the understanding of fundamental questions in biology and medicine. In this paper, the authors perform gene expression analysis and apply two hybrid GA-fuzzy approaches to classify gene expression data. Both are based on fuzzy if-then rule bases but they differ in the way these rule bases are optimised. The authors employ both a Michigan style approach, where single rules are handled as individuals in the population of the genetic algorithm, and a Pittsburgh type algorithm, which treats whole rule sets as individuals. Experimental results show that both approaches achieve good classification accuracy but that the Michigan style algorithm clearly outperforms the Pittsburgh classifier.


Leukemia ◽  
2011 ◽  
Vol 25 (9) ◽  
pp. 1459-1466 ◽  
Author(s):  
M C Lanasa ◽  
S D Allgood ◽  
S L Slager ◽  
S S Dave ◽  
C Love ◽  
...  

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