CD44 splice variant v8-10 as a marker of serous ovarian cancer prognosis

Amanda Sosulski, Heiko Horn, Lihua Zhang, Caroline Coletti, Vinod Vathipadiekal, Cesar M. Castro, Michael J. Birrer, Osamu Nagano, Hideyuki Saya, Kasper Lage, Patricia K. Donahoe, David Pépin

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Abstract

CD44 is a transmembrane hyaluronic acid receptor gene that encodes over 100 different tissue-specific protein isoforms. The most ubiquitous, CD44 standard, has been used as a cancer stem cell marker in ovarian and other cancers. Expression of the epithelial CD44 variant containing exons v8-10 (CD44v8-10) has been associated with more chemoresistant and metastatic tumors in gastrointestinal and breast cancers, but its role in ovarian cancer is unknown; we therefore investigated its use as a prognostic marker in this disease. The gene expression profiles of 254 tumor samples from The Cancer Genome Atlas RNAseqV2 were analyzed for the presence of CD44 isoforms. A trend for longer survival was observed in patients with high expression of CD44 isoforms that include exons v8-10. Immunohistochemical (IHC) analysis of tumors for presence of CD44v8-10 was performed on an independent cohort of 210 patients with high-grade serous ovarian cancer using a tumor tissue microarray. Patient stratification based on software analysis of staining revealed a statistically significant increase in survival in patients with the highest levels of transmembrane protein expression (top 10 or 20%) compared to those with the lowest expression (bottom 10 and 20%) (p = 0.0181, p = 0.0262 respectively). Expression of CD44v8-10 in primary ovarian cancer cell lines was correlated with a predominantly epithelial phenotype characterized by high expression of epithelial markers and low expression of mesenchymal markers by qPCR, Western blot, and IHC. Conversely, detection of proteolytically cleaved and soluble extracellular domain of CD44v8-10 in patient ascites samples was correlated with significantly worse prognosis (p

Original languageEnglish
Article numbere0156595
JournalPLoS One
Volume11
Issue number6
DOIs
Publication statusPublished - 2016 Jun 1

Fingerprint

ovarian neoplasms
Ovarian Neoplasms
prognosis
Exons
exons
Tumors
neoplasms
Protein Isoforms
Neoplasms
Genes
Tissue
Gastrointestinal Neoplasms
Survival
Neoplastic Stem Cells
Atlases
hyaluronic acid
protein isoforms
Hyaluronic Acid
Microarrays
Stem cells

ASJC Scopus subject areas

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

Cite this

Sosulski, A., Horn, H., Zhang, L., Coletti, C., Vathipadiekal, V., Castro, C. M., ... Pépin, D. (2016). CD44 splice variant v8-10 as a marker of serous ovarian cancer prognosis. PLoS One, 11(6), [e0156595]. https://doi.org/10.1371/journal.pone.0156595

CD44 splice variant v8-10 as a marker of serous ovarian cancer prognosis. / Sosulski, Amanda; Horn, Heiko; Zhang, Lihua; Coletti, Caroline; Vathipadiekal, Vinod; Castro, Cesar M.; Birrer, Michael J.; Nagano, Osamu; Saya, Hideyuki; Lage, Kasper; Donahoe, Patricia K.; Pépin, David.

In: PLoS One, Vol. 11, No. 6, e0156595, 01.06.2016.

Research output: Contribution to journalArticle

Sosulski, A, Horn, H, Zhang, L, Coletti, C, Vathipadiekal, V, Castro, CM, Birrer, MJ, Nagano, O, Saya, H, Lage, K, Donahoe, PK & Pépin, D 2016, 'CD44 splice variant v8-10 as a marker of serous ovarian cancer prognosis', PLoS One, vol. 11, no. 6, e0156595. https://doi.org/10.1371/journal.pone.0156595
Sosulski A, Horn H, Zhang L, Coletti C, Vathipadiekal V, Castro CM et al. CD44 splice variant v8-10 as a marker of serous ovarian cancer prognosis. PLoS One. 2016 Jun 1;11(6). e0156595. https://doi.org/10.1371/journal.pone.0156595
Sosulski, Amanda ; Horn, Heiko ; Zhang, Lihua ; Coletti, Caroline ; Vathipadiekal, Vinod ; Castro, Cesar M. ; Birrer, Michael J. ; Nagano, Osamu ; Saya, Hideyuki ; Lage, Kasper ; Donahoe, Patricia K. ; Pépin, David. / CD44 splice variant v8-10 as a marker of serous ovarian cancer prognosis. In: PLoS One. 2016 ; Vol. 11, No. 6.
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