Imperial College London
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DrPaulaCunnea

Faculty of Medicine, Department of Surgery & Cancer

Advanced Research Fellow
 
 
 
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Contact

 

+44 (0)20 7594 1548p.cunnea

 
 
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Location

 

Institute of Reproductive and Developmental BiologyHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Hu:2021:10.1158/1078-0432.ccr-20-2782,
author = {Hu, Z and Cunnea, P and Zhong, Z and Lu, H and Osagie, OI and Campo, L and Artibani, M and Nixon, K and Ploski, J and Santana, Gonzalez L and Alsaadi, A and Wietek, N and Damato, S and Dhar, S and Blagden, SP and Yau, C and Hester, J and Albukhari, A and Aboagye, EO and Fotopoulou, C and Ahmed, A},
doi = {10.1158/1078-0432.ccr-20-2782},
journal = {Clinical Cancer Research},
pages = {1570--1579},
title = {The Oxford Classic links epithelial-to-mesenchymal transition to immunosuppression in poor prognosis ovarian cancers},
url = {http://dx.doi.org/10.1158/1078-0432.ccr-20-2782},
volume = {27},
year = {2021}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Purpose: Using RNA sequencing, we recently developed the 52-gene–based Oxford classifier of carcinoma of the ovary (Oxford Classic, OxC) for molecular stratification of serous ovarian cancers (SOCs) based on the molecular profiles of their cell of origin in the fallopian tube epithelium. Here, we developed a 52-gene NanoString panel for the OxC to test the robustness of the classifier.Experimental Design: We measured the expression of the 52 genes in an independent cohort of prospectively collected SOC samples (n = 150) from a homogenous cohort who were treated with maximal debulking surgery and chemotherapy. We performed data mining of published expression profiles of SOCs and validated the classifier results on tissue arrays comprising 137 SOCs.Results: We found evidence of profound nongenetic heterogeneity in SOCs. Approximately 20% of SOCs were classified as epithelial-to-mesenchymal transition–high (EMT-high) tumors, which were associated with poor survival. This was independent of established prognostic factors, such as tumor stage, tumor grade, and residual disease after surgery (HR, 3.3; P = 0.02). Mining expression data of 593 patients revealed a significant association between the EMT scores of tumors and the estimated fraction of alternatively activated macrophages (M2; P < 0.0001), suggesting a mechanistic link between immunosuppression and poor prognosis in EMT-high tumors.Conclusions: The OxC-defined EMT-high SOCs carry particularly poor prognosis independent of established clinical parameters. These tumors are associated with high frequency of immunosuppressive macrophages, suggesting a potential therapeutic target to improve clinical outcome.
AU  - Hu,Z
AU  - Cunnea,P
AU  - Zhong,Z
AU  - Lu,H
AU  - Osagie,OI
AU  - Campo,L
AU  - Artibani,M
AU  - Nixon,K
AU  - Ploski,J
AU  - Santana,Gonzalez L
AU  - Alsaadi,A
AU  - Wietek,N
AU  - Damato,S
AU  - Dhar,S
AU  - Blagden,SP
AU  - Yau,C
AU  - Hester,J
AU  - Albukhari,A
AU  - Aboagye,EO
AU  - Fotopoulou,C
AU  - Ahmed,A
DO  - 10.1158/1078-0432.ccr-20-2782
EP  - 1579
PY  - 2021///
SN  - 1078-0432
SP  - 1570
TI  - The Oxford Classic links epithelial-to-mesenchymal transition to immunosuppression in poor prognosis ovarian cancers
T2  - Clinical Cancer Research
UR  - http://dx.doi.org/10.1158/1078-0432.ccr-20-2782
UR  - http://hdl.handle.net/10044/1/86017
VL  - 27
ER  -
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