Project description:We compared miRNAs expression in mucinous ovarian cancer cell between treated with siPRKRA and contrl siRNA. We hypothesize that PRKRA regulates chemosensitivity in mucinous ovarian cancer. Therefore, we aim to idetify the PRKRA-mediated miRNA which regulate chemosensitivity in mucinous ovarian cancer.
Project description:Mucinous cystic neoplasms (MCN) remain a major riddle in hepato-pancreato-biliary pathology. These cystic tumors are defined by their mucinous epithelium and ovarian-like stroma, with an estimated 10% risk of progression to invasive carcinoma. The origin of the ovarian stroma remains a subject of debate. In this study, we conducted immunohistochemical profiling, targeted DNA sequencing, and genome-wide DNA methylation analysis on a cohort of 15 pancreatic MCNs (MCN-P) and 6 hepatic MCNs (MCN-L). Unsupervised analysis of DNA methylation profiles of pancreatic neoplasms (11 entities and normal pancreatic tissue from 224 unique samples) revealed that MCN-P predominantly forms a distinct group. In the DNA methylation landscape of liver tumors, encompassing 5 tumor types and normal bile duct tissue from 136 unique samples, MCN-L demonstrated a specific methylation profile when compared to all other entities. Furthermore, within the DNA methylation landscape of ovarian tumors—featuring 5 tumor types, normal fallopian tube, and normal ovarian tissue from 90 unique samples—we found that both MCN-P and MCN-L grouped with mucinous ovarian carcinoma and mucinous borderline ovarian tumors. Notably, low-grade MCNs exhibited greater DNA methylation similarities to mucinous borderline ovarian tumors, while high-grade or invasive MCNs were primarily associated with mucinous ovarian carcinomas. When analyzing all samples together (19 tumor types and 4 normal tissue types, n = 430), MCNs similarly grouped with mucinous ovarian tumors and normal ovarian tissue. Additionally, in anetwork analysis of differentially methylated probes indicated that MCN-P and MCN-L share significant methylomic traits, closely resembling mucinous ovarian tumors. In conclusion, our findings highlight that MCN-P and MCN-L are distinct entities in the landscape of pancreatic and hepatic tumors and show DNA methylation profile similarities with mucinous ovarian tumors, suggesting a potential common origin.
Project description:Gene expression profile of 8 mucinous borderline ovarian tumors and 9 mucinous ovarian carcinomas. Frozen tumor samples were laser-capture microdissected for their epithelial component. RNA was extracted. Gene expression profiling was completed using Affymetrix U133 Plus 2.0 oligonucleotide microarrays.
Project description:Knocking down of CSE1L made ovarian cancer cells, but not other cancer and normal cell lines, sensitized to cisplatin and triggered apoptosis. The nuclear localization in ovarian cancer cells suggested that CSE1L might primarily regulate transcription. . Using microarrays, we evaluated the expression profiles of CSE1L silenced SK-OV-3 and TOV-21G cells
Project description:Introduction: Mucinous tumors are the second most common form of epithelial ovarian tumor, yet the cell of origin for this histological sub-type remains undetermined. While these tumors are thought to arise through a stepwise progression from benign cystadenoma to borderline tumor to invasive carcinoma, few studies have attempted to comprehensively characterize the genetic changes specific to this subtype or its precursors. Methods: To explore the spectrum of genomic alterations common to mucinous tumors we performed high resolution genome-wide copy number analysis, mutation screening by Sanger sequencing and immunohistochemistry on a series of primary ovarian mucinous cystadenomas (n=20) and borderline tumors (n=22). Results: Integration of copy number data, targeted mutation screening of RAS/RAF pathway members and immunohistochemistry reveals that p16 loss and RAS/RAF pathway alterations are highly recurrent events that occur early during mucinous tumor development. The frequency of concurrence of these events was observed in 40% of benign cystadenomas and 68% of borderline tumors. Conclusions: This study is the largest and highest resolution analysis of mucinous benign and borderline tumors performed to date and provides strong support for these lesions being precursors of primary ovarian mucinous adenocarcinoma. The high level of uniformity in the molecular events underlying the pathogenesis of mucinous ovarian tumors provides an opportunity for treatments targeting specific mutations and pathways. Copy number data was generated for 42 mucinous ovarian tumours (20 benign, 22 borderline). Epithelial and stromal DNA from the tumours and matched-normal lymphocyte DNA were all analysed. Processed/normalized data for the germline DNA samples are not provided because they themselves are normalised to a diploid copy number, making all the probe values 2, which is not informative.
Project description:Introduction: Mucinous tumors are the second most common form of epithelial ovarian tumor, yet the cell of origin for this histological sub-type remains undetermined. While these tumors are thought to arise through a stepwise progression from benign cystadenoma to borderline tumor to invasive carcinoma, few studies have attempted to comprehensively characterize the genetic changes specific to this subtype or its precursors. Methods: To explore the spectrum of genomic alterations common to mucinous tumors we performed high resolution genome-wide copy number analysis, mutation screening by Sanger sequencing and immunohistochemistry on a series of primary ovarian mucinous cystadenomas (n=20) and borderline tumors (n=22). Results: Integration of copy number data, targeted mutation screening of RAS/RAF pathway members and immunohistochemistry reveals that p16 loss and RAS/RAF pathway alterations are highly recurrent events that occur early during mucinous tumor development. The frequency of concurrence of these events was observed in 40% of benign cystadenomas and 68% of borderline tumors. Conclusions: This study is the largest and highest resolution analysis of mucinous benign and borderline tumors performed to date and provides strong support for these lesions being precursors of primary ovarian mucinous adenocarcinoma. The high level of uniformity in the molecular events underlying the pathogenesis of mucinous ovarian tumors provides an opportunity for treatments targeting specific mutations and pathways.
Project description:Ovarian cancer cells treated with CDDP showed up-regulation of IRF-1 and IRF-7. The expression of putative IRF-1 target genes was modulated. CDDP triggered nuclear translocation of IRF-1 and IRF-1 silencing re-orchestrated the expression profiles of CDDP treated cells. Using microarrays, we evaluated the expression profiles of IRF-1 silenced SK-OV-3.
Project description:MicroRNA (miRNA) expression profiles have been described in pancreatic ductal adenocarcinoma (PDAC), but these have not been compared with premalignant lesions. We wished to identify miRNA expression profiles in pancreatic cystic tumors with low malignant potential (serous microcystic adenomas) and high malignant potential (mucinous cystadenoma and intraductal papillary mucinous neoplasm (IPMN)) and compare these to PDAC and carcinoma-ex-IPMN (CEI).
Project description:MicroRNA (miRNA) expression profiles have been described in pancreatic ductal adenocarcinoma (PDAC), but these have not been compared with premalignant lesions. We wished to identify miRNA expression profiles in pancreatic cystic tumors with low malignant potential (serous microcystic adenomas) and high malignant potential (mucinous cystadenoma and intraductal papillary mucinous neoplasm (IPMN)) and compare these to PDAC and carcinoma-ex-IPMN (CEI). n= 20 samples Benign Pancreatic Cystic Tumour (n=7 Microcystic, n= 6 Mucinous, n= 7 IPMN) were compared with n= 9 samples of carcinoma ex IPMN and n= 14 samples of pancreatic cancer (adenocarcinoma) for known homo sapiens miRNAs (mirbase 13).