scholarly journals The impact of androgen receptor (AR) and histone deacetylase 1 (HDAC1) expression on the prognosis of ductal carcinoma in situ (DCIS)

2020 ◽  
Author(s):  
Choong Man Lee ◽  
Jisun Kim ◽  
Yang Soon Park ◽  
Gyung Won Yoon ◽  
Hwi Gyeong Jo ◽  
...  
Keyword(s):  
Gene Expression ◽  
Androgen Receptor ◽  
Histone Deacetylase ◽  
Gene Expression Analysis ◽  
Ductal Carcinoma ◽  
External Validation ◽  
Fold Change ◽  
Histone Deacetylase 1

Abstract Background Ductal carcinoma in situ (DCIS) display favorable outcome but little is known about the factors associated with invasive recurrence. To identify better prognostic biomarkers, we performed gene expression analysis followed by immunohistochemistry (IHC) staining validation. Methods Differential gene expression (DGE) analysis of 24 pure DCIS patients was performed using a nanostring platform. RNA was extracted from paraffin blocks from age/estrogen receptor matched recurrence-free (n=16) and invasive-recurrence (n=8) cases (disease-free interval >5 years). External validation was done among independent 61 cases, invasive-recurrence (n=16) and recurrence-free (n=45) pure DCIS cases by IHC staining. Results Eight differentially expressed genes were found statistically significant (log 2-fold change <–1 or >1 and p<0.001). Less than ½ fold expression of CUL1, AR, RPS27A, CTNNB1, MAP3K1, PRKACA, GNG12, MGMT genes were observed in REC cases compared to NED cases. Androgen receptor (AR) and histone deacetylase 1 (HDAC1) were selected for external validation (AR: log 2-fold change –1.35, p<0.001, and HDAC1; log 2-fold change –0.774, p<0.001). AR and HDAC1 protein expression was externally validated by IHC staining of 61 pure DCIS cases (16 invasive-recurrence versus 45 recurrence-free). Absence of AR and high HDAC1 expression was an independent risk factor for invasive recurrence (hazard ratio 5.04, 95% CI: 1.24, 20.4; p=0.023, hazard ratio 3.07, 95% CI: 1.04, 9.04; p=0.042). High nuclear grade (NG 3) was also associated with long term invasive recurrence. Conclusion Comparative gene expression analysis of pure DCIS revealed 8 genes differentially expressed among recurred cases. Immunohistochemistry validation within an independent cohort suggests that, absence of AR and overexpression of HDAC1 was associated with greater risk of long term invasive recurrence among pure DCIS.

scholarly journals The Impact of Androgen Receptor and Histone Deacetylase 1 Expression on the Prognosis of Ductal Carcinoma In Situ

2020 ◽  
Vol 23 (6) ◽  
pp. 610
Author(s):  
Choong Man Lee ◽  
Il Yong Chung ◽  
Yangsoon Park ◽  
Keong Won Yun ◽  
Hwi Gyeong Jo ◽  
...  
Keyword(s):  
Androgen Receptor ◽  
Histone Deacetylase ◽  
Ductal Carcinoma In Situ ◽  
Carcinoma In Situ ◽  
Ductal Carcinoma ◽  
Histone Deacetylase 1 ◽  
The Impact

The impact of androgen receptor (AR) expression on the prognosis of ductal carcinoma in situ (DCIS).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e14731-e14731
Author(s):  
Choong Man Lee ◽  
Jisun Kim ◽  
Hwi Gyeong Jo ◽  
Hye Jin Park ◽  
Sae Byul Lee ◽  
...  
Keyword(s):  
Gene Expression ◽  
Androgen Receptor ◽  
Differentially Expressed Genes ◽  
Expression Analysis ◽  
Ductal Carcinoma In Situ ◽  
Carcinoma In Situ ◽  
Gene Expression Analysis ◽  
Ductal Carcinoma ◽  
Enrichment Analysis

e14731 Background: Ductal carcinoma in situ (DCIS) display favorable outcome while little is known about the factors associated with invasive recurrence. To identify better prognostic biomarkers we performed gene expression analysis followed by immunohistochemistry (IHC) staining validation. Methods: Differential gene expression analysis of 29 pure DCIS patients was performed using nanostring platform. RNA was extracted from paraffin blocks from age/size matched 11 recurrence-free and 18 invasive-recurrence cases (disease free interval > 5 years). Gene annotation enrichment analysis was done for differentially expressed genes (DEG) using DAVID. Eighty-two pure DCIS cases were selected for external validation by IHC staining. Allred score cutoff 1 was used for survival analysis. Results: Ninety-nine differentially expressed genes were found statistically significant (p-value < 0.05). Androgen receptor (AR) gene, which encodes a transcription factor AR, has recently been highlighted as a favorable prognostic marker and a therapeutic target in invasive tumor (fold change = - 1.35, p < 0.001). AR protein expression was externally validated by IHC staining of 82 pure DCIS cases (24 invasive-recurrence versus 58 recurrence-free). Similar to gene expression analysis result, patients with invasive recurrence showed lower AR staining score than recurrence-free patients (p = 0.007). Cox regression analysis showed lower AR level as an independent risk factor of long-term invasive recurrence (HR 7.43, 95%CI 1.50 – 36.62). Gene enrichment analysis revealed enrichment of kinase pathway and cell cycle pathway in recurred cases (Enrichment Score = 2.43, 2.41 respectively). Conclusions: DEG pattern was observed among pure DCIS cases. AR may serve as a prognostic biomarker and targeting kinase, cell proliferation may be effective for higher risk DCIS patients.

Abstract 212: Prophylactic Anti-inflammatory Treatment Attenuates The Neuroinflammatory And Behavioral Effects Of Silent Cerebral Infarction

2014 ◽  
Vol 115 (suppl_1) ◽  
Author(s):  
Christina L Nemeth ◽  
Gretchen N Neigh
Keyword(s):  
Gene Expression ◽  
Cardiac Surgery ◽  
Open Field ◽  
Treatment Strategies ◽  
Fold Change ◽  
Inflammatory Activity ◽  
Central Tendency ◽  
Negative Consequences ◽  
Anti Inflammatory

Silent brain infarction is a frequent complication of cardiac surgery and is associated with mood changes and cognitive disruption. Microsphere embolism (ME) rodent models recapitulate both the diffuse ischemic infarcts and the delayed subtle behavioral disturbances characteristic to silent infarction (SI). Previously, we have shown that ME leads to increased hippocampal inflammation, weakening of the blood brain barrier, and the infiltration of peripherally circulating inflammatory cells in rats. Given long-term increases in inflammatory activity following SI, the current study tests the efficacy of anti-inflammatory versus anti-depressant treatment strategies to reduce the inflammatory and behavioral sequelae of injury. Adult rats were administered either chronic meloxicam (preferential COX-2 inhibitor) or fluoxetine (SSRI) beginning five days prior to ME surgeries. After a two week recovery, animals were tested for anxiety-like behaviors in the open field paradigm and the hippocampus was examined for gene expression of inflammatory cytokines. Meloxicam treated animals showed a decrease in hippocampal gene expression of inflammatory markers (SPP1; p = 0.0272) and greater than a 3-fold change improvement in open field central tendency (p = 0.0003). No differences in inflammatory gene expression were observed in fluoxetine treated animals (SPP1; p = 0.3288); however, fluoxetine treatment resulted in a 2-fold change improvement in open field central tendency (p = 0.0138) suggesting that while both treatment strategies attenuate SI induced behavioral disruption, only meloxicam acts via inflammatory mechanisms. Given the long term negative consequences of increased central and peripheral inflammatory activity, the data suggest that anti-inflammatory therapeutic strategies may benefit patients at risk for SI as well as cardiac surgery candidates.

Ductal Carcinoma-In-Situ: Long-Term Results of Breast-Conserving Therapy

2000 ◽  
Vol 7 (9) ◽  
pp. 656-664 ◽  
Author(s):  
Nadeem Q. Mirza ◽  
Georges Vlastos ◽  
Funda Meric ◽  
Aysegul A. Sahin ◽  
S. Eva Singletary ◽  
...  
Keyword(s):  
Ductal Carcinoma In Situ ◽  
Carcinoma In Situ ◽  
Ductal Carcinoma ◽  
Breast Conserving Therapy ◽  
Long Term Results

Intragraft vasculitis and gene expression analysis: Association with acute rejection and prediction of mortality in long-term heart transplantation

2018 ◽  
Vol 32 (10) ◽  
pp. e13373
Author(s):  
Hui Tzu Lin-Wang ◽  
Reginaldo Cipullo ◽  
João Italo Dias França ◽  
Marco Aurelio Finger ◽  
Joao Manoel Rossi Neto ◽  
...  
Keyword(s):  
Gene Expression ◽  
Acute Rejection ◽  
Heart Transplantation ◽  
Expression Analysis ◽  
Gene Expression Analysis ◽  
Prediction Of Mortality

scholarly journals Outcome of long term active surveillance for estrogen receptor-positive ductal carcinoma in situ

The Breast ◽  
2011 ◽  
Vol 20 (6) ◽  
pp. 529-533 ◽  
Author(s):  
Anna F. Meyerson ◽  
Juan N. Lessing ◽  
Kaoru Itakura ◽  
Nola M. Hylton ◽  
Dulcy E. Wolverton ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Active Surveillance ◽  
Ductal Carcinoma In Situ ◽  
Carcinoma In Situ ◽  
Ductal Carcinoma ◽  
Estrogen Receptor Positive
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