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Expression profiling of primary and metastatic ovarian tumors reveals differences indicative of aggressive disease

Expression profiling of primary and metastatic ovarian tumors reveals differences indicative of aggressive disease
Expression profiling of primary and metastatic ovarian tumors reveals differences indicative of aggressive disease
The behavior and genetics of serous epithelial ovarian cancer (EOC) metastasis, the form of the disease lethal to patients, is poorly understood. The unique properties of metastases are critical to understand to improve treatments of the disease that remains in patients after debulking surgery. We sought to identify the genetic and phenotypic landscape of metastatic progression of EOC to understand how metastases compare to primary tumors. DNA copy number and mRNA expression differences between matched primary human tumors and omental metastases, collected at the same time during debulking surgery before chemotherapy, were measured using microarrays. qPCR and immunohistochemistry validated findings. Pathway analysis of mRNA expression revealed metastatic cancer cells are more proliferative and less apoptotic than primary tumors, perhaps explaining the aggressive nature of these lesions. Most cases had copy number aberrations (CNAs) that differed between primary and metastatic tumors, but we did not detect CNAs that are recurrent across cases. A six gene expression signature distinguishes primary from metastatic tumors and predicts overall survival in independent datasets. The genetic differences between primary and metastatic tumors, yet common expression changes, suggest that the major clone in metastases is not the same as in primary tumors, but the cancer cells adapt to the omentum similarly. Together, these data highlight how ovarian tumors develop into a distinct, more aggressive metastatic state that should be considered for therapy development.
1932-6203
e94476
Brodsky, Alexander S.
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Fischer, Andrew
20b487bf-e73c-4eff-925c-cc2ade341865
Miller, Daniel H.
b8922c61-f933-48a6-94f2-3b60ba2b0d02
Vang, Souriya
4b061075-cb73-4b6a-ac26-9a1c7e326310
MacLaughlan, Shannon
c8096b9e-3ea3-40d0-bb91-724fff817b9b
Wu, Hsin-Tu
ed96992d-153d-4ae0-bf3a-166120bbe10a
Yu, Jovian
e4b37421-a9a8-4ab2-9d69-7f243dd9e440
Steinhoff, Margaret
2c4d5288-a80e-49e0-a338-5211f5aa3f4f
Collins, Colin
c8ad5faf-696f-4fa0-8363-d698a7cbc63e
Smith, Peter J.S.
003de469-9420-4f12-8f0e-8e8d76d28d6c
Raphael, Benjamin J.
f3ddaa9d-7bfd-42a5-886e-6d64b5cee626
Brard, Laurent
0f3d972b-ff5a-4ad2-854e-f3b8216e2424
Brodsky, Alexander S.
7ec45f2e-016e-43d4-906d-a2c8516bd52b
Fischer, Andrew
20b487bf-e73c-4eff-925c-cc2ade341865
Miller, Daniel H.
b8922c61-f933-48a6-94f2-3b60ba2b0d02
Vang, Souriya
4b061075-cb73-4b6a-ac26-9a1c7e326310
MacLaughlan, Shannon
c8096b9e-3ea3-40d0-bb91-724fff817b9b
Wu, Hsin-Tu
ed96992d-153d-4ae0-bf3a-166120bbe10a
Yu, Jovian
e4b37421-a9a8-4ab2-9d69-7f243dd9e440
Steinhoff, Margaret
2c4d5288-a80e-49e0-a338-5211f5aa3f4f
Collins, Colin
c8ad5faf-696f-4fa0-8363-d698a7cbc63e
Smith, Peter J.S.
003de469-9420-4f12-8f0e-8e8d76d28d6c
Raphael, Benjamin J.
f3ddaa9d-7bfd-42a5-886e-6d64b5cee626
Brard, Laurent
0f3d972b-ff5a-4ad2-854e-f3b8216e2424

Brodsky, Alexander S., Fischer, Andrew, Miller, Daniel H., Vang, Souriya, MacLaughlan, Shannon, Wu, Hsin-Tu, Yu, Jovian, Steinhoff, Margaret, Collins, Colin, Smith, Peter J.S., Raphael, Benjamin J. and Brard, Laurent (2014) Expression profiling of primary and metastatic ovarian tumors reveals differences indicative of aggressive disease. PLoS ONE, 9 (4), e94476. (doi:10.1371/journal.pone.0094476).

Record type: Article

Abstract

The behavior and genetics of serous epithelial ovarian cancer (EOC) metastasis, the form of the disease lethal to patients, is poorly understood. The unique properties of metastases are critical to understand to improve treatments of the disease that remains in patients after debulking surgery. We sought to identify the genetic and phenotypic landscape of metastatic progression of EOC to understand how metastases compare to primary tumors. DNA copy number and mRNA expression differences between matched primary human tumors and omental metastases, collected at the same time during debulking surgery before chemotherapy, were measured using microarrays. qPCR and immunohistochemistry validated findings. Pathway analysis of mRNA expression revealed metastatic cancer cells are more proliferative and less apoptotic than primary tumors, perhaps explaining the aggressive nature of these lesions. Most cases had copy number aberrations (CNAs) that differed between primary and metastatic tumors, but we did not detect CNAs that are recurrent across cases. A six gene expression signature distinguishes primary from metastatic tumors and predicts overall survival in independent datasets. The genetic differences between primary and metastatic tumors, yet common expression changes, suggest that the major clone in metastases is not the same as in primary tumors, but the cancer cells adapt to the omentum similarly. Together, these data highlight how ovarian tumors develop into a distinct, more aggressive metastatic state that should be considered for therapy development.

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Accepted/In Press date: 16 March 2014
Published date: 14 April 2014
Organisations: Centre for Biological Sciences

Identifiers

Local EPrints ID: 364882
URI: http://eprints.soton.ac.uk/id/eprint/364882
ISSN: 1932-6203
PURE UUID: 7c524bf6-14ef-4a11-8c39-f7411e8cf191
ORCID for Peter J.S. Smith: ORCID iD orcid.org/0000-0003-4400-6853

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Date deposited: 15 May 2014 15:50
Last modified: 17 Dec 2019 01:39

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Contributors

Author: Alexander S. Brodsky
Author: Andrew Fischer
Author: Daniel H. Miller
Author: Souriya Vang
Author: Shannon MacLaughlan
Author: Hsin-Tu Wu
Author: Jovian Yu
Author: Margaret Steinhoff
Author: Colin Collins
Author: Benjamin J. Raphael
Author: Laurent Brard

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