Peritoneal tumor spread in serous ovarian cancer-epithelial mesenchymal status and outcome
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1245400 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:In this study we aimed to analyze the biological mechanisms underlying apparently different modes of peritoneal tumor spread in serous ovarian cancer: miliary (widespread, millet-like lesions) versus non-miliary (bigger, exophytically growing implants). Tumor tissues and ascites from 23 chemotherapy naive patients were analyzed by RNA-sequencing and flow cytometry. On the basis of differential gene expression between miliary and non-miliary, gene signatures were developed. A calculated tumor spread factor revealed a significant independent negative impact of miliary spread on overall survival (HR 3.77; CI95 1.14–12.39; p = 0.029) in an independent cohort of 165 serous ovarian cancer patients. Comparing previously published epithelial-mesenchymal transition (EMT) gene signatures, non-miliary spread correlated significantly with a reduced epithelial status. We conclude that serous ovarian cancer is a heterogeneous disease with distinct modes of peritoneal tumor spread, differing not only in clinical appearance, but also in molecular characteristics and outcome. EMT, peritoneal inflammation status, and therapeutic options are discussed. Significance: More than half of serous epithelial ovarian cancer patients present with a newly described type of intraperitoneal tumor spread, associated with differences in the inflammation status, activated oncogenic pathways, lack of EMT, and thus reduced overall survival. Both, the diminished immune reaction and the enhanced epithelial and malignant characteristics of the tumor cells open new avenues for therapeutic options and strategies, like Catumaxomab, already in clinical use.
2025-04-03 | GSE293643 | GEO
Project description:UnlabelledIn this study we aimed to analyze the biological mechanisms underlying apparently different modes of peritoneal tumor spread in serous ovarian cancer: miliary (widespread, millet-like lesions) versus non-miliary (bigger, exophytically growing implants). Tumor tissues and ascites from 23 chemotherapy naive patients were analyzed by RNA-sequencing and flow cytometry. On the basis of differential gene expression between miliary and non-miliary, gene signatures were developed. A calculated tumor spread factor revealed a significant independent negative impact of miliary spread on overall survival (HR 3.77; CI95 1.14-12.39; p = 0.029) in an independent cohort of 165 serous ovarian cancer patients. Comparing previously published epithelial-mesenchymal transition (EMT) gene signatures, non-miliary spread correlated significantly with a reduced epithelial status. We conclude that serous ovarian cancer is a heterogeneous disease with distinct modes of peritoneal tumor spread, differing not only in clinical appearance, but also in molecular characteristics and outcome. EMT, peritoneal inflammation status, and therapeutic options are discussed.SignificanceMore than half of serous epithelial ovarian cancer patients present with a newly described type of intraperitoneal tumor spread, associated with differences in the inflammation status, activated oncogenic pathways, lack of EMT, and thus reduced overall survival. Both, the diminished immune reaction and the enhanced epithelial and malignant characteristics of the tumor cells open new avenues for therapeutic options and strategies, like Catumaxomab, already in clinical use.
| S-EPMC4627306 | biostudies-literature
Project description:The presence of tumor cells in effusions within serosal cavities is a clinical manifestation of advanced-stage cancer and is generally associated with poor survival. Identifying molecular targets may help to design efficient treatments to eradicate these aggressive cancer cells and improve patient survival. Using a state-of-the-art Taqman-based qRT-PCR assay, we investigated the multidrug resistance (MDR) transcriptome of 32 unpaired ovarian serous carcinoma effusion samples obtained at diagnosis or at disease recurrence following chemotherapy. MDR genes were selected a priori based on an extensive curation of the literature published during the last three decades. We found three gene signatures with a statistically significant correlation with overall survival (OS), response to treatment (complete response - CR vs. other), and progression free survival (PFS). The median log-rank p-values for the signatures were 0.023, 0.034, and 0.008, respectively. No correlation was found with residual tumor status after cytoreductive surgery, treatment (with or without chemotherapy) and stage defined according to the International Federation of Gynecology and Obstetrics. Further analyses demonstrated that gene expression alone can effectively predict the survival outcome of women with ovarian serous carcinoma (OS: log-rank p=0.0000 and PFS: log-rank p=0.002). Interestingly, the signature for overall survival is the same in patients at first presentation and those who had chemotherapy and relapsed. This pilot study highlights two new gene signatures that may help in optimizing the treatment for ovarian carcinoma patients with effusions. In the study presented here, effusion samples were obtained from 32 patients diagnosed with serous ovarian carcinoma (n=25), primary peritoneal serous carcinoma (n=6) or tubal serous carcinoma (n=1). They were accrued at the Division of Pathology in the Norwegian Radium Hospital from 2000-2006. RNA was used to study the expression profile of 381 multidrug resistant-related genes.
2011-11-17 | E-GEOD-29702 | biostudies-arrayexpress
Project description:HGSOC, the most aggressive form of OC, is characterized by insidious onset, rapid intraperitoneal spread and development of massive ascites. Peritoneal adhesion was considered as the first step of abdominal metastasis, underscoring that only tumor cells gain access to peritoneal adherence contribute to metastasis. Studies on ovarian cancer progression were mainly focused on the primary and metastatic tumor cells, while understanding of the ascitic tumor cells is limited. We hypothesized that uncovering the gene expression profiles of ascitic tumor cells from high grade serous ovarian cancer patients will allow us to understand more specifically their unique phenotype which mediates the peritoneal adhesion. In this study, gene expression profiling was completed for 15 magnetic sorted tumor cells samples from matched primary tumors, ascites and metastases of 5 high grade serous ovarian cancer patients. By comparing the expression data from ascitic tumor cells with primary and metastasis tumor cells, we identified a set of differential expressed genes in ovarian ascitic tumor cells advantageous for peritoneal adhesion and metastasis. Further study revealed that ascites microenvironment modulated the ascitic tumor cells phenotype and contributed to ovarian cancer dissemination through facilitating CAFs in formation of compact spheroids with ascitic tumor cells. We used microarrays to profile the expression of 15 matched tumor cells samples in order to identify molecular alteration between primary tumor cells, ascitic tumor cells and metastatic tumor cells in high grade serous ovarian cancer.
2017-12-19 | GSE73064 | GEO
Project description:Natural killer cells were extracted from the peritoneal cells of ascites of high grade serous ovarian carcinoma patients.
2024-12-31 | E-MTAB-14053 | biostudies-arrayexpress
Project description:The transcriptomes of three immortalized ovarian surface epithelial cell lines (iOSE, PMID: 17266044) and primary OSE cells (Innoprot, Derio, Spain) and four immortalized fallopian tube secretory epithelial (iFTE) cell lines (PMID: 21502498, 22936217) were compared. RNA-sequencing was done from rRNA depleted total RNA (Ribo-Zero rRNA Removal Kit) to approx. 20 million 50 bp paired end reads per sample. A discriminative gene expression signature comprised of 211 genes was developed and used to classify isolated and EpCAM enriched primary ovarian cancer cells (PMID: 25991672). Impact of this signature on overall survival was assessed from several publicly available ovarian cancer gene expression data sets. Background: High grade serous ovarian cancer (HGSOC) is characterized by extensive local, i.e. peritoneal, tumor spread, manifested in two different clinical presentations, miliary (many millet sized peritoneal implants) and non-miliary (few large exophytically growing peritoneal nodes), and an overall unfavorable outcome. HGSOC is thought to arise from fallopian tube secretory epithelial cells, via so called serous tubal intraepithelial carcinomas (STICs) but an ovarian origin was never ruled out for at least some cases. Comparative transcriptome analyses of isolated tumor cells from fresh HGSOC tissues and (immortalized) ovarian surface epithelial and fallopian tube secretory epithelial cell lines revealed a close relation between putative origin and tumor spread characteristic, i.e. miliary from tubes and non-miliary from ovaries.
2016-12-15 | E-MTAB-5240 | biostudies-arrayexpress
Project description:In mouse peritoneal and other serous cavities, the transcription factor Gata6 drives the identity of the major cavity resident population of macrophages, with a smaller subset of cavity-resident macrophages dependent on the transcription factor Irf4. Here we showed that GATA6+ macrophages in the human peritoneum were rare, regardless of age. Instead, more human peritoneal macrophages aligned with mouse CD206+ LYVE1+ cavity macrophages that represent a differentiation stage just preceding expression of Gata6. Low abundance of CD206+ macrophages was retained in C57BL/6J mice fed a high-fat diet or in wild-captured mice, suggesting that differences between serous cavity-resident macrophages in humans and mice were not environmental. Irf4-dependent mouse serous cavity macrophages aligned closely with human CD1c+CD14+CD64+ peritoneal cells that, in turn, resembled human peritoneal CD1c+CD14-CD64- cDC2. Thus, major populations of serous cavity-resident mononuclear phagocytes in humans and mice shared common features but the proportions of different macrophage differentiation stages greatly differ between the two species and DC2-like cells were especially prominent in humans.
2023-10-17 | GSE228030 | GEO
Project description:Genomic variants associated with angina and health status outcome after MI
| PRJNA429310 | ENA
Project description:Genomic variants associated with angina and health status outcome after MI
| PRJNA429311 | ENA
Project description:GATA2 expression in endometrial serous carcinoma cells correlates with patient outcome. Depletion of GATA2 in patient-derived endometrial serous carcinoma cell lines correlates with invasive potential. As GATA2 is a transcription factor, we hypothesize that GATA2-dependent target genes normally suppress invasion in endometrial serous carcinoma.
2025-03-06 | GSE264610 | GEO