Lysophosphatidic acid-induced transcriptional profile represents serous epithelial ovarian carcinoma and worsened prognosis

Mandi M. Murph, Wenbin Liu, Shuangxing Yu, Yiling Lu, Hassan Hall, Bryan T. Hennessy, John Lahad, Marci Schaner, Åslaug Helland, Gunnar Kristenen, Anne Lise Bøorresen-Dale, Gordon Mills

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

Background: Lysophosphatidic acid (LPA) governs a number of physiologic and pathophysiological processes. Malignant ascites fluid is rich in LPA, and LPA receptors are aberrantly expressed by ovarian cancer cells, implicating LPA in the initiation and progression of ovarian cancer. However, there is an absence of systematic data critically analyzing the transcriptional changes induced by LPA in ovarian cancer. Methodology and Principal Findings: In this study, gene expression profiling was used to examine LPA-mediated transcription by exogenously adding LPA to human epithelial ovarian cancer cells for 24 h to mimic long-term stimulation in the tumor microenvironment. The resultant transcriptional profile comprised a 39-gene signature that closely correlated to serous epithelial ovarian carcinoma. Hierarchical clustering of ovarian cancer patient specimens demonstrated that the signature is associated with worsened prognosis. Patients with LPA-signature-positive ovarian tumors have reduced disease-specific and progression-free survival times. They have a higher frequency of stage IIIc serous carcinoma and a greater proportion is deceased. Among the 39-gene signature, a group of seven genes associated with cell adhesion recapitulated the results. Out of those seven, claudin-1, an adhesion molecule and phenotypic epithelial marker, is the only independent biomarker of serous epithelial ovarian carcinoma. Knockdown of claudin-1 expression in ovarian cancer cells reduces LPA-mediated cellular adhesion, enhances suspended cells and reduces LPA-mediated migration. Conclusions: The data suggest that transcriptional events mediated by LPA in the tumor microenvironment influence tumor progression through modulation of cell adhesion molecules like claudin-1 and, for the first time, report an LPA-mediated expression signature in ovarian cancer that predicts a worse prognosis.

Original languageEnglish (US)
Article numbere5583
JournalPLoS One
Volume4
Issue number5
DOIs
StatePublished - May 15 2009
Externally publishedYes

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prognosis
carcinoma
ovarian neoplasms
Carcinoma
acids
Ovarian Neoplasms
Claudin-1
Tumors
cell adhesion
Tumor Microenvironment
Genes
Cells
neoplasms
lysophosphatidic acid
Adhesion
Lysophosphatidic Acid Receptors
Cell adhesion
Cell Adhesion Molecules
genes
Gene Expression Profiling

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Lysophosphatidic acid-induced transcriptional profile represents serous epithelial ovarian carcinoma and worsened prognosis. / Murph, Mandi M.; Liu, Wenbin; Yu, Shuangxing; Lu, Yiling; Hall, Hassan; Hennessy, Bryan T.; Lahad, John; Schaner, Marci; Helland, Åslaug; Kristenen, Gunnar; Bøorresen-Dale, Anne Lise; Mills, Gordon.

In: PLoS One, Vol. 4, No. 5, e5583, 15.05.2009.

Research output: Contribution to journalArticle

Murph, MM, Liu, W, Yu, S, Lu, Y, Hall, H, Hennessy, BT, Lahad, J, Schaner, M, Helland, Å, Kristenen, G, Bøorresen-Dale, AL & Mills, G 2009, 'Lysophosphatidic acid-induced transcriptional profile represents serous epithelial ovarian carcinoma and worsened prognosis', PLoS One, vol. 4, no. 5, e5583. https://doi.org/10.1371/journal.pone.0005583
Murph, Mandi M. ; Liu, Wenbin ; Yu, Shuangxing ; Lu, Yiling ; Hall, Hassan ; Hennessy, Bryan T. ; Lahad, John ; Schaner, Marci ; Helland, Åslaug ; Kristenen, Gunnar ; Bøorresen-Dale, Anne Lise ; Mills, Gordon. / Lysophosphatidic acid-induced transcriptional profile represents serous epithelial ovarian carcinoma and worsened prognosis. In: PLoS One. 2009 ; Vol. 4, No. 5.
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AU - Hall, Hassan

AU - Hennessy, Bryan T.

AU - Lahad, John

AU - Schaner, Marci

AU - Helland, Åslaug

AU - Kristenen, Gunnar

AU - Bøorresen-Dale, Anne Lise

AU - Mills, Gordon

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