Project description:Ovarian clear cell carcinoma (OCCC) is an epithelial ovarian cancer (EOC) histology having distinct pathology, biology, and molecular footprints. OCCC is chemo-resistant and has the worst stage-adjusted prognosis amongst EOC. Yet, treatment for OCCC patients is no different than other EOC. As OCCC incidence rate has significantly increase in recent decades, it is critical to find OCCC-tailored therapeutic. However, majority of EOC gene expression molecular subtypes (GEMS) studies for personalized medicine focused on the high grade serous histology, and studies in OCCC GEMS were of small sample size. Using more than 200 OCCC gene expression profiles, we identified two OCCC subtypes: EpiCC—epithelial-like, early stage, good prognosis, relative higher rate of gene mutations in SWI/SNF complex; and MesCC—mesenchymal-like, late stage, and poor prognosis. The differential prognosis between EpiCC and MesCC could be observed as early as stage IC. Genetic, copy number and transcriptome profiling showed that both EpiCC and MesCC carried OCCC-associated aberrations. The EpiCC and MesCC are reproducible in validation cohorts and OCCC cell lines. Cell lines assays showed that MesCC is more proliferative and more anoikis resistant than EpiCC. Both EpiCC and MesCC are resistant to cisplatin. Applying the OCCC subtypes to TCGA 534 renal clear cell carcinoma indicated interoperability of the subtyping scheme, and revealed preferential response of EpiCC to sorafenib, and MesCC to bevacizumab. The EpiCC and MesCC classification shows promise in prognostication utility especially for stage IC OCCC patients, and warrants further investigation for subtype-tailored treatment regimen.
Project description:Clear cell ovarian carcinoma (CCOC) is the second most common subtype of epithelial ovarian carcinoma. Late stage CCOC is not responsive to gold-standard chemotherapy and result in suboptimal outcome for patients. In-depth molecular insight is urgently needed to stratify the disease and drive therapeutic development. We conducted global proteomics in 192 cases of CCOC comparing to other epithelial ovarian carcinoma subtypes.
Project description:A collection of 100 ovarian cancer sample gene expression data from Singapore. Frozen archival epithelial ovarian cancer tumors samples from Department of Obstetrics & Gynecology, National University of Singapore dated from 2006 to 2014 were collected and subjected to microarray analysis.
Project description:ARID1A, which encodes a component of the SWI/SNF chromatin-remodeling complex, is commonly mutated in ovarian clear cell carcinoma and many other cancer types. We used label-free LC-MS/MS to identify ARID1A-dependent proteome changes in ovarian clear cell carcinoma cell lines. In our first analysis, we compared ARID1A-wildtype ovarian clear cell carcinoma cell line OVCA429 with or without ARID1A CRISPR knockout. In a complementary analysis, we compared ARID1A-mutated ovarian clear cell carcinoma cell line OVISE with or without ARID1A overexpression using a tet-inducible promoter.
Project description:To investigate the microRNA profiles of ovarian clear cell carcinoma (OCCC), microRNA sequencing was performed using formalin-fixed, paraffin-embedded (FFPE) and fresh-frozen clinical samples. Moreover, patient-derived xenograft (PDX) tumors and cell lines were also investigated.
Project description:Ovarian cancer is a malignant gynecologic disease rarely diagnosed in the early stages. Among ovarian cancers, clear cell carcinoma has a poor prognosis due to its malignant potential. MicroRNAs (miRNAs) regulate gene expression in cells by suppressing the translation of the target gene or by degrading the target mRNA. They are also secreted from the cells in the blood, binding to the proteins or lipids and assisting in cell-cell communication. Hence, serum miRNAs can also be diagnostic biomarkers for ovarian cancer. This study investigated and identified specific miRNAs for ovarian clear cell carcinoma and compared them to those of ovarian endometrioma in healthy patients. CA125, an ovarian tumor marker, did not differ between patients with ovarian clear cell carcinoma, endometriosis, or healthy controls. Four miRNAs (miR-146a-5p, miR-191-5p, miR-484, and miR-574-3p) were analyzed. The miR-146a-5p and miR-191-5p expression levels were significantly increased in the serum samples from the patients with ovarian clear cell carcinoma compared to the healthy controls but not in the patients with endometriosis (P < 0.05). Furthermore, the bioinformatics analysis showed that CCND2 and NOTCH2 were the candidate target genes of miR 146a-5p and miR-191-5p. In conclusion, our results showed that miR 146a-5p and miR-191-5p might be useful as early and non-invasive diagnostic tools in ovarian clear cell carcinoma. These miRNAs can help in distinguishing between ovarian clear cell carcinoma and ovarian endometrioma. To the best of our knowledge, no studies have screened any candidates specifically for clear cell carcinoma.