Abstract
BackgroundEpithelial ovarian cancer (EOC) constitutes more than 90% of ovarian cancers and is associated with high mortality. EOC comprises a heterogeneous group of tumours, and the causes and molecular pathology are essentially unknown. Improved insight into the molecular characteristics of the different subgroups of EOC is urgently needed, and should eventually lead to earlier diagnosis as well as more individualized and effective treatments. Previously, we reported a limited number of mRNAs strongly upregulated in human osteosarcomas and other malignancies, and six were selected to be tested for a possible association with three subgroups of ovarian carcinomas and clinical parameters.Methodology/Principal FindingsThe six selected mRNAs were quantified by RT-qPCR in biopsies from eleven poorly differentiated serous carcinomas (PDSC, stage III–IV), twelve moderately differentiated serous carcinomas (MDSC, stage III–IV) and eight clear cell carcinomas (CCC, stage I–IV) of the ovary. Superficial scrapings from six normal ovaries (SNO), as well as biopsies from three normal ovaries (BNO) and three benign ovarian cysts (BBOC) were analyzed for comparison. The gene expression level was related to the histological and clinical parameters of human ovarian carcinoma samples. One of the mRNAs, DNA polymerase delta 2 small subunit (POLD2), was increased in average 2.5- to almost 20-fold in MDSC and PDSC, respectively, paralleling the degree of dedifferentiation and concordant with a poor prognosis. Except for POLD2, the serous carcinomas showed a similar transcription profile, being clearly different from CCC. Another mRNA, Killer-specific secretory protein of 37 kDa (KSP37) showed six- to eight-fold higher levels in CCC stage I compared with the more advanced staged carcinomas, and correlated positively with an improved clinical outcome.Conclusions/SignificanceWe have identified two biomarkers which are markedly upregulated in two subgroups of ovarian carcinomas and are also associated with stage and outcome. The results suggest that POLD2 and KSP37 might be potential prognostic biomarkers.
Highlights
In Norway and the United States, ovarian cancer is the fourth and fifth most frequent cause of cancer death in women, respectively [1,2]
Mean expression levels of six selected mRNAs in three subgroups of ovarian carcinomas compared with three different control groups Expression levels of the six selected mRNAs in PDSC, MDSC
These significantly differentially expressed mRNAs were all upregulated in PDSC and MDSC, while downregulated in CCC
Summary
In Norway and the United States, ovarian cancer is the fourth and fifth most frequent cause of cancer death in women, respectively [1,2]. Type I tumours include highly differentiated serous carcinomas, mucinous carcinomas, endometroid carcinomas, clear cell carcinomas and malignant Brenner tumours. They are thought to arise from precursor lesions such as cystadenomas, borderline tumours or endometriosis and suggested to be a result of mutations in e.g. KRAS, BRAF, CTNNB1 or PTEN genes [4,6,8,9]. Ovarian carcinogenesis appears to be associated with abnormalities in multiple gene families How these genetic alterations are reflected in changes in transcriptional activity and carcinogenesis are not understood. EOC comprises a heterogeneous group of tumours, and the causes and molecular pathology are essentially unknown. We reported a limited number of mRNAs strongly upregulated in human osteosarcomas and other malignancies, and six were selected to be tested for a possible association with three subgroups of ovarian carcinomas and clinical parameters
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