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The role of RNA-binding motif 3 in epithelial ovarian cancer: A biomarker discovery approach

Ehlén, Åsa LU (2011) In Lund University, Faculty of Medicine Doctoral Dissertation Series 2011:9.
Abstract
Epithelial ovarian cancer (EOC) is the most lethal of all gynaecological malignancies and there is an urgent need to develop new prognostic and treatment predictive biomarkers for a more efficient therapy. The discovery of the RNA-binding motif protein 3 (RBM3) as a putative cancer biomarker was based on its differential expression in various cancer forms in the Human Protein Atlas (HPA). Further investigations demonstrated an association between high nuclear RBM3 expression and improved survival in breast cancer.



In this thesis, the prognostic value of RBM3 was examined at the mRNA and protein levels in two independent EOC cohorts, whereby increased expression of RBM3 was found to be associated with a favorable... (More)
Epithelial ovarian cancer (EOC) is the most lethal of all gynaecological malignancies and there is an urgent need to develop new prognostic and treatment predictive biomarkers for a more efficient therapy. The discovery of the RNA-binding motif protein 3 (RBM3) as a putative cancer biomarker was based on its differential expression in various cancer forms in the Human Protein Atlas (HPA). Further investigations demonstrated an association between high nuclear RBM3 expression and improved survival in breast cancer.



In this thesis, the prognostic value of RBM3 was examined at the mRNA and protein levels in two independent EOC cohorts, whereby increased expression of RBM3 was found to be associated with a favorable prognosis. Further in vitro studies revealed a sensitizing effect of RBM3 to the platinum compound cisplatin. With the aim to indentify underlying biological processes associated with RBM3 expression in EOC we performed a gene set enrichment analysis and uncovered an association between RBM3 expression and several cellular processes involved in the maintenance of DNA integrity, including DNA replication, chromatin remodeling and DNA integrity checkpoint. The RBM3 regulated genes were subsequently screened in the HPA and proteins displaying a differential expression pattern among EOC samples were further analyzed in EOC cell lines. An inverse correlation was observed between RBM3 and MCM3, Chk1 and Chk2. The prognostic value of theses markers was investigated in two EOC cohorts revealing an association between Chk1, Chk2 and MCM3 expression and an impaired survival.

In addition, we investigated a possible involvement of RBM3 in the cell cycle process and observed a delay in S-phase progression upon downregulation of RBM3 in a synchronized cell population, suggesting a possible role of RBM3 in DNA replication. (Less)
Please use this url to cite or link to this publication:
author
supervisor
opponent
  • PhD Shoshan, Maria, Cancer Center KArolinska CCk, Karolinska University Hospital, Stockholm, Sweden
organization
publishing date
type
Thesis
publication status
published
subject
keywords
DNA integrity checkpoint, cisplatin treatment, prognostic/predictive marker, RBM3, epithelial ovarian cancer, Chk1, Chk2, MCM3
in
Lund University, Faculty of Medicine Doctoral Dissertation Series
volume
2011:9
pages
118 pages
defense location
Main lecture hall, Pathology Building, Entrance 78, 2 fl. UMAS, Malmö
defense date
2011-01-28 09:00
ISSN
1652-8220
ISBN
978-91-86671-58-7
language
English
LU publication?
yes
id
54178579-7a5d-4809-ab6e-cf4a34c36564 (old id 1759666)
date added to LUP
2011-01-10 12:09:16
date last changed
2016-09-19 08:45:01
@phdthesis{54178579-7a5d-4809-ab6e-cf4a34c36564,
  abstract     = {Epithelial ovarian cancer (EOC) is the most lethal of all gynaecological malignancies and there is an urgent need to develop new prognostic and treatment predictive biomarkers for a more efficient therapy. The discovery of the RNA-binding motif protein 3 (RBM3) as a putative cancer biomarker was based on its differential expression in various cancer forms in the Human Protein Atlas (HPA). Further investigations demonstrated an association between high nuclear RBM3 expression and improved survival in breast cancer. <br/><br>
<br/><br>
In this thesis, the prognostic value of RBM3 was examined at the mRNA and protein levels in two independent EOC cohorts, whereby increased expression of RBM3 was found to be associated with a favorable prognosis. Further in vitro studies revealed a sensitizing effect of RBM3 to the platinum compound cisplatin. With the aim to indentify underlying biological processes associated with RBM3 expression in EOC we performed a gene set enrichment analysis and uncovered an association between RBM3 expression and several cellular processes involved in the maintenance of DNA integrity, including DNA replication, chromatin remodeling and DNA integrity checkpoint. The RBM3 regulated genes were subsequently screened in the HPA and proteins displaying a differential expression pattern among EOC samples were further analyzed in EOC cell lines. An inverse correlation was observed between RBM3 and MCM3, Chk1 and Chk2. The prognostic value of theses markers was investigated in two EOC cohorts revealing an association between Chk1, Chk2 and MCM3 expression and an impaired survival.<br/><br>
In addition, we investigated a possible involvement of RBM3 in the cell cycle process and observed a delay in S-phase progression upon downregulation of RBM3 in a synchronized cell population, suggesting a possible role of RBM3 in DNA replication.},
  author       = {Ehlén, Åsa},
  isbn         = {978-91-86671-58-7},
  issn         = {1652-8220},
  keyword      = {DNA integrity checkpoint,cisplatin treatment,prognostic/predictive marker,RBM3,epithelial ovarian cancer,Chk1,Chk2,MCM3},
  language     = {eng},
  pages        = {118},
  school       = {Lund University},
  series       = {Lund University, Faculty of Medicine Doctoral Dissertation Series},
  title        = {The role of RNA-binding motif 3 in epithelial ovarian cancer: A biomarker discovery approach},
  volume       = {2011:9},
  year         = {2011},
}