EMT markers within M1 diagnostic prostate biopsies correlate with stem like phenotype and loss of AR signalling
BAUS ePoster online library. Hiew K. 06/30/16; 132021; P11-6
Mr. Kenneth Hiew
Mr. Kenneth Hiew
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Abstract
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P11-6

Background & Aims:

Epithelial-Mesenchymal Transition(EMT), as characterised by loss of cell polarity and cell-cell adhesion, and the gain of invasion and migratory abilities, stem like characteristics and resistance to chemotherapeutic agents, is critical to metastasis. Our previous work showed Vimentin and E-cadherin were prognostic in diagnostic biopsies.  This report examines whether EMT status correlates with altered expression of androgen signalling and stem cell-like genes in primary diagnostic prostate samples with M1 disease at first presentation.

 

Materials & Methods:

Regions of tumour and adjacent stroma were macro-dissected from 20 FFPE primary M1 CaP diagnostic needle prostate biopsies for RNA extraction and subsequent NanoString© platform interrogation of EMT effectors (E-Cadherin, Fibronectin, α-SMA), EMT inducers (TWIST, ZEB1, ZEB2, SNAI1,SNAI2), Stem Cell like (CD44) and AR signalling (AR,ARV7,KLK2,KLK3,KLK4) genes. EMT status was determined by calculating the Vimentin/E-cadherin mRNA expression ratio.  The correlation between EMT status and other genes was analysed with Pearsons coefficient correlation.

 

Result:

Expression of EMT inducers (ZEB1:r=0.537, p=0.015; ZEB2:r=0.750, p=0.000; SNAI2:r=0.604, p=0.005), the EMT effector a-SMA  (r=0.635, p=0.003), CD44 (r= 0.472,p=0.036) correlated with EMT status.  AR genes (AR,ARV7) exhibited an inverse correlation with EMT status (AR:r= -0.542, p= 0.013: ARV7:r=-0.502, p=0.024). The kallikrein family showed a mixed response with KLK4 correlating with EMT status (r=0.474,p=0.035) but not KLK2 & KLK3.

 

Conclusion:

Our results suggest EMT status is associated with the expression levels of AR signalling and stem cell like genes in diagnostic needle biopsies of men with primary M1 CaP at first presentation. 

P11-6

Background & Aims:

Epithelial-Mesenchymal Transition(EMT), as characterised by loss of cell polarity and cell-cell adhesion, and the gain of invasion and migratory abilities, stem like characteristics and resistance to chemotherapeutic agents, is critical to metastasis. Our previous work showed Vimentin and E-cadherin were prognostic in diagnostic biopsies.  This report examines whether EMT status correlates with altered expression of androgen signalling and stem cell-like genes in primary diagnostic prostate samples with M1 disease at first presentation.

 

Materials & Methods:

Regions of tumour and adjacent stroma were macro-dissected from 20 FFPE primary M1 CaP diagnostic needle prostate biopsies for RNA extraction and subsequent NanoString© platform interrogation of EMT effectors (E-Cadherin, Fibronectin, α-SMA), EMT inducers (TWIST, ZEB1, ZEB2, SNAI1,SNAI2), Stem Cell like (CD44) and AR signalling (AR,ARV7,KLK2,KLK3,KLK4) genes. EMT status was determined by calculating the Vimentin/E-cadherin mRNA expression ratio.  The correlation between EMT status and other genes was analysed with Pearsons coefficient correlation.

 

Result:

Expression of EMT inducers (ZEB1:r=0.537, p=0.015; ZEB2:r=0.750, p=0.000; SNAI2:r=0.604, p=0.005), the EMT effector a-SMA  (r=0.635, p=0.003), CD44 (r= 0.472,p=0.036) correlated with EMT status.  AR genes (AR,ARV7) exhibited an inverse correlation with EMT status (AR:r= -0.542, p= 0.013: ARV7:r=-0.502, p=0.024). The kallikrein family showed a mixed response with KLK4 correlating with EMT status (r=0.474,p=0.035) but not KLK2 & KLK3.

 

Conclusion:

Our results suggest EMT status is associated with the expression levels of AR signalling and stem cell like genes in diagnostic needle biopsies of men with primary M1 CaP at first presentation. 

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