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Whole blood RNA expression profiles in ovarian cancer patients with or without residual tumors after primary cytoreductive surgery
Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Departments of Laboratory Medicine, Section for Clinical Chemistry, Örebro University Hospital, Örebro, Sweden.ORCID iD: 0000-0003-4879-528X
Departments of Gynecological Oncology, Örebro University Hospital, Örebro, Sweden.
Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Departments of Laboratory Medicine, Section for Clinical Chemistry, Örebro University Hospital, Örebro, Sweden.
2012 (English)In: Oncology Reports, ISSN 1021-335X, E-ISSN 1791-2431, Vol. 27, no 5, p. 1331-1335Article in journal (Refereed) Published
Abstract [en]

Significant improvements in the treatment results of ovarian cancer have been achieved during the last decades, but further improvements require additional methods identifying signs of the disease and its biological behavior, preferably by a simple blood test. We hypothesized that peripheral blood leukocytes may express genes that carry such clinical information. Therefore, we studied the relative gene expressions of 168 cancer- and metastasis-specific genes in blood samples from ovarian cancer patients with different prognoses after primary cytoreductive surgery. Total RNA was extracted from whole blood and the relative gene expression profile of 168 genes were analyzed using real-time qPCR assays. Two groups of patients were analyzed; one group with residual tumor mass after primary surgery, and one group where the tumor was macroscopically radically resected, resulting in no visible tumor mass left behind. The group with the remaining tumor mass after surgery showed significantly different gene expression profiles compared to the group with no remaining tumor mass. Differences were noted for the metastasis associated 1 family, member 2 gene (MTA2), the TNF, alpha-catenin, interleukin 1 beta, the KiSS-1 metastasis suppressor and the matrix metalloproteinase 10 genes. All genes were downregulated with a fold-change between 1.15 to 1.57; there were no upregulated genes. Thus, a signature of genes involved in metastasis, invasion and inflammation was found to be significantly downregulated in native unstimulated blood leukocytes from ovarian cancer patients with a poor prognosis. Preoperatively it may serve as a guide to the biology of the tumor and postoperatively in the optimization of adjuvant treatment of ovarian cancer patients.

Place, publisher, year, edition, pages
Athens, Greece: Spandidos Publications Ltd. , 2012. Vol. 27, no 5, p. 1331-1335
Keywords [en]
Seropapillary ovarian cancer, residual tumor, leukocyte gene expression, whole blood RNA expression
National Category
Medical and Health Sciences Cancer and Oncology
Research subject
Biomedicine
Identifiers
URN: urn:nbn:se:oru:diva-23093DOI: 10.3892/or.2012.1680ISI: 000302202600005PubMedID: 22322362Scopus ID: 2-s2.0-84858269622OAI: oai:DiVA.org:oru-23093DiVA, id: diva2:529709
Note

Funding Agencies:

Lions' Cancer Research Foundation 

Research Committee of Orebro County Council 

Available from: 2012-05-31 Created: 2012-05-31 Last updated: 2019-03-29Bibliographically approved
In thesis
1. Clinical studies of RNA as a prognostic and diagnostic marker for disease
Open this publication in new window or tab >>Clinical studies of RNA as a prognostic and diagnostic marker for disease
2017 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Technologies for RNA detection are evolving rapidly and gives an op-portunity for discovery of new markers for early detection of complex diseases. Today in clinical work we rely on signs and symptoms in com-bination with the measurement of protein levels for diagnosis. The quick turnaround time of mRNA synthesis may provide an earlier diagnostic signal than protein-based biomarkers assays, in acute dramatic condi-tions such as acute mesenteric ischemia (AMI), for early detection of cancer, as prognostic tool in cancer treatment and as an aid in difficult diagnosis of unknown origin.

The main goals of this thesis was to apply a whole genome approach to study different complex diseases to evaluate the applicability of RNA as a diagnostic or prognostic marker for disease, preferably from an easily accessible source such as peripheral blood. This was investigated in an animal model with induced AMI, a cohort of ovarian cancer patients and in a single-patient study of a girl with a severe inflammatory syn-drome.

Through this thesis we have gained insight into how gene expression is regulated in ischemic intestinal tissue.

We found that a peripheral blood test can distinguish between ovarian cancer patients with or without residual tumour mass after surgery with the help of expression analysis of six genes. We also found that gene expressions of three genes can predict overall survival in peripheral whole blood from ovarian cancer patients. And that gene expression profiles indeed can significantly distinguish between two groups of high and low risk ovarian cancer. In the single-patient study, we tried but failed to device a successful treatment before it was too late. Neverthe-less, the things we learned and the case studies that were published may serve as a diagnostic tool for clinicians facing similar syndromes.

Place, publisher, year, edition, pages
Örebro: Örebro University, 2017. p. 57
Series
Örebro Studies in Medicine, ISSN 1652-4063 ; 168
Keywords
gene expression, ovarian cancer, hypercalprotectinaemia, hyperzincaemia, ischemia, biomarker
National Category
Other Basic Medicine
Identifiers
urn:nbn:se:oru:diva-61626 (URN)978-91-7529-219-9 (ISBN)
Public defence
2017-12-15, Örebro universitet, Campus USÖ, hörsal C1, Södra Grev Rosengatan 32, Örebro, 09:15 (Swedish)
Opponent
Supervisors
Available from: 2017-10-18 Created: 2017-10-18 Last updated: 2018-01-13Bibliographically approved

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Isaksson, Helena S.Nilsson, Torbjörn K.

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