Transcriptional profiling analysis of clear cell ovarian cancer

Abstract

Ovarian cancer is one of the most lethal gynecological malignancies. Several histotypes with different molecular and morphological features representing this cancer type make it very challenging from clinico-pathological perspective. Thus there is need for better prognostic and molecular markers.

Ovarian clear cell carcinoma (OCCC) is a subtype with poor prognosis and very distinct phenotype when compared to others. Clear cell ovarian cancer (type I) is often detected in early stages, when curative treatment is possible. Patients with clear cell ovarian cancer present in latestage disease, on the other hand, have a poor response to conventional platinum-based chemotherapy. Together with its specific pathology determined by cells with clear cytoplasm and hob nails cells, it makes it a histotype of a great interest. Aim of this study was to determine the gene expression profile for clear cell ovarian carcinoma by comparing it with other histotypes. Also, because clear cell ovarian carcinoma shares some features with renal clear cell carcinoma (ccRCC), comprehensive analysis was done to identify these similarities and to understand the biology behind the clear cells.

We used four different ovarian and two renal cancer data sets from publicly available databases. All our analyses were done in R. Significance Analysis of Microarray (SAM) and Gene Enrichment Set Analysis (GSEA) were used for each data set to detect the gene regulations and pathways involved in clear cells and results were compared.

Our results suggest that although clear cells have significant aberrations in SWI/SNF chromatin remodeling complex, hypoxia and chemoresistance, there is a strong heterogeneity within ovarian and renal clear cells tumors.

Popular Abstract

Not clear at all! Clear cell ovarian cancer

Ovarian cancer is one of the most lethal gynecological malignancies. Several histotypes with different molecular and morphological features representing this cancer type make it very challenging from clinico-pathological perspective. Thus there is need for better prognostic and molecular markers. Here, we focused on one specific subtype – clear cell carcinoma and our aim was to determine its gene expression profile by comparing it with other histotypes.

Ovarian cancer is a malignancy that develops in the lower abdomen in women. Among all the gynecological malignancies, ovarian cancer is the most lethal one. It is hard to diagnose because physiologically the tumor arises in a quite spacious body area, so it is usually captured in already advanced stage, and symptoms like persistent bloating, abdominal or pelvic pain can be connected to various, less harmful diseases.

Ovarian clear cell carcinoma (OCCC) is a subtype with poor prognosis in advanced stages and very distinct phenotype when compared to others. When detected in early stages, curative treatment is possible. Patients with OCCC present in late- stage disease, on the other hand, have a poor response to conventional platinum-based chemotherapy. Together with its specific pathology determined by cells with clear cytoplasm with high glycogen content and hob nails cells, it makes it a histotype of a great interest. Clear cell ovarian carcinoma also shares some features with renal clear cell carcinoma (ccRCC), which was also included in this study.

Gene expression profile of clear cells ovarian cancer
We used four ovarian and two renal cancer microarray data sets (lllumina and Affymetrix platforms) publicly available from Gene Expression Omnibus (GEO) database. Essentially, microarrays measure the amount of labeled sequences, expressed genes in biological samples. Various statistical tools can then be used to analyse these data. Significance Analysis of Microarray (SAM) and Gene Set Enrichment Analysis (GSEA) were used for each data set to detect the gene regulations and pathways involved in clear cell carcinomas and results from these methods were compared.

We came to the conclusion that morphology and biology of ovarian clear cell tumors are best defined by defections in SWI/SNF chromatin remodelling complexes, chemoresistance and oxidative stress. Although there are many shared features between ovarian and renal clear cells, lots of them are a result of multi-step processes and can vary tremendously. Our results also suggest, that there is a strong heterogeneity even within clear cells tumors.

Advisor: Ingrid Hedenfalk
Masters Degree Project 60 credits in Bioinformatics 2015
Department of Biology, Lund University

• author: Sichmanova, Zuzana
• supervisor: Ingrid Hedenfalk
• organization: Degree Projects in Bioinformatics
• course: BINP32 20142
• year: 2015
• type: H2 - Master's Degree (Two Years)
• subject: Biology and Life Sciences
• language: English
• id: 7756598
• date added to LUP: 2015-08-07 15:16:16
• date last changed: 2015-08-07 15:16:16