ArticlePloS one2016
CD44 Splice Variant v8-10 as a Marker of Serous Ovarian Cancer Prognosis.
Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 47 citations in OpenAlex.
- Multifaceted roles of CD44 in cancer progression and targeted therapeutic strategies.Experimental & molecular medicine · 2026Review
- Exploring the Potential of Natural Killer Cell-Based Immunotherapy in Targeting High-Grade Serous Ovarian Carcinomas.Vaccines · 2024Review
- The v8-10 variant isoform of CD44 is selectively expressed in the normal human colonic stem cell niche and frequently is overexpressed in colon carcinomas during tumor development.Cancer biology & therapy · 2023Article
- The Role of Cancer Stem Cell Markers in Ovarian Cancer.Cancers · 2023Review
- Cancer Stem Cell Markers-Clinical Relevance and Prognostic Value in High-Grade Serous Ovarian Cancer (HGSOC) Based on The Cancer Genome Atlas Analysis.International journal of molecular sciences · 2023Article
- Targeting CD44 Variant 5 with an Antibody-Drug Conjugate Is an Effective Therapeutic Strategy for Intrahepatic Cholangiocarcinoma.Cancer research · 2023Article
- RNA-binding proteins regulating the CD44 alternative splicing.Frontiers in molecular biosciences · 2023Review
- Comprehensive characterization of 11 prognostic alternative splicing events in ovarian cancer interacted with the immune microenvironment.Scientific reports · 2022Article
- Alternative splicing acts as an independent prognosticator in ovarian carcinoma.Scientific reports · 2021Article
- A genome-wide strategy to identify causes and consequences of retrotransposon expression finds activation by BRCA1 in ovarian cancer.NAR cancer · 2021Article
- Research Progress in Prognostic Factors and Biomarkers of Ovarian Cancer.Journal of Cancer · 2021Review
- CD44v8-10 mRNA contained in serum exosomes as a diagnostic marker for docetaxel resistance in prostate cancer patients.Heliyon · 2020Article
- Metabolic Plasticity in Ovarian Cancer Stem Cells.Cancers · 2020Article
- The Role of Cancer Stem Cells in Radiation Resistance.Frontiers in oncology · 2020Review
- Article
- Determining the prognostic significance of alternative splicing events in soft tissue sarcoma using data from The Cancer Genome Atlas.Journal of translational medicine · 2019Article
- Layer-by-layer nanoparticles for novel delivery of cisplatin and PARP inhibitors for platinum-based drug resistance therapy in ovarian cancer.Bioengineering & translational medicine · 2019Article
- Platform-Independent Classification System to Predict Molecular Subtypes of High-Grade Serous Ovarian Carcinoma.JCO clinical cancer informatics · 2019Article
- Aberrant mRNA splicing generates oncogenic RNA isoforms and contributes to the development and progression of cholangiocarcinoma.Biomedical reports · 2019Article
- Alternative-splicing defects in cancer: Splicing regulators and their downstream targets, guiding the way to novel cancer therapeutics.Wiley interdisciplinary reviews. RNA · 2018Review
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
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<0.05). Therefore, presence of transmembrane CD44v8-10 on the surface of primary tumor cells may be a marker of a highly epithelial tumor with better prognosis while enzymatic cleavage of CD44v8-10, as detected by presence of the soluble extracellular domain in ascites fluid, may be indicative of a more metastatic disease and worse prognosis.
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