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Whole genome expression profiling of blood cells in ovarian cancer patients: prognostic impact of the CYP1B1, MTSS1, NCALD, and NOP14 genes
Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Örebro University Hospital. Department of Oncology.ORCID iD: 0000-0002-5063-631X
Department of Medical Biosciences/Clinical Chemistry, Umeå University, Umeå, Sweden.
2014 (English)In: OncoTarget, ISSN 1949-2553, E-ISSN 1949-2553, Vol. 5, no 12, p. 4040-4049Article in journal (Refereed) Published
Abstract [en]

Ovarian cancer patients with different tumor stages and cell differentiation might be distinguished from each other by gene expression profiles in whole blood cell mRNA by the Affymetrix Human Gene 1.0 ST Array. We also examined if there is any association with other clinical variables, response to therapy, and residual tumor burden after surgery. Patients were divided into two groups, one with poor prognosis, advanced stage and poorly differentiated tumors (n = 22), and one group with good prognosis, early stage and well-to medium differentiated tumors (n = 11). Six genes were found to be differentially expressed: the PDIA3, LYAR, NOP14, NCALD and MTSS1 genes were down-regulated and the CYP1B1 gene expression was up-regulated in the poor prognosis group, all with p value <0.05, adjusted for mass comparison. In survival analyses, CYP1B1, MTSS1, NCALD and NOP14 remained significantly different (p<0.05). Patient groups did not differ in any transcript related to acute phase or immune responses. This minimal gene expression signature of prognostic ovarian cancer-related genes opens up an avenue for more practicable monitoring of ovarian cancer patients by simple peripheral blood tests, which may evolve into a tool to guide selection of curative and postoperative supportive therapies.

Place, publisher, year, edition, pages
Impact press, 2014. Vol. 5, no 12, p. 4040-4049
Keyword [en]
ovarian cancer, whole genome profiling, prognosis, mRNA, NCALD, MTSS1, PDA3, CYP1B1, NOP14, LYAR
National Category
Cancer and Oncology
Research subject
Oncology
Identifiers
URN: urn:nbn:se:oru:diva-36179ISI: 000339055200007PubMedID: 24961659Scopus ID: 2-s2.0-84905090787OAI: oai:DiVA.org:oru-36179DiVA, id: diva2:742626
Note

Funding Agencies:

Research Committee of Örebro County Council

Foundation for Gynecological Oncology, Örebro

Lions' Cancer Research Foundation, Uppsala-Örebro

Available from: 2014-09-02 Created: 2014-08-28 Last updated: 2017-12-05Bibliographically 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
Keyword
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.Sorbe, BengtNilsson, Torbjörn K.

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