ABSTRACT: Comparative transcriptome analysis links distinct peritoneal tumor spread types, miliary and non-miliary, with putative origin, tubes and ovaries, in high grade serous ovarian cancer
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.
Project description:High-grade serous cancer (HGSC) progresses to advanced stages without symptoms and the 5-year survival rate is a dismal 30%. Recent studies of ovaries and fallopian tubes in patients with BRCA mutations revealed that pre-metastatic HGSC is found almost exclusively in the fallopian tube in a lesion termed “serous tubal intraepithelial carcinoma” or STIC. We have performed laser captured microdissection (LCM) of normal oviduct, STIC and invasive serous cancer from each patient. A whole-genome transcriptome analysis comparing between normal oviduct, STIC and invasive serous cancer were performed. We demonstrated a clear molecular progression from normal to STIC, which shared the gene expression patterns with invasive serous cancer, suggesting a new set of genes as basis of novel detection and therapeutic approaches to HGSC at its earliest stage.
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.
Project description:Self-inhibition of pollen tubes plays a key role in SI, but the underlying mechanism in Camellia oleifera is poorly understood. Collection of secreted proteins from Camellia oleifera pollen tubes and ovaries for high-throughput sequencing.
Project description:High grade serous ovarian cancer (HGSOC) is characterized by late stage, rapid progression, easy drug resistance, high mortality and recurrence rate. Tubal secretory cells have always been considered as the origin cells of HGSOC, due to the high heterogeneity of the latter, the type and mechanism of cell origin is poorly confirmed. Combined with single-nuclei RNA sequencing (snRNA-seq) and Bulk tissue transcriptome sequencing, we expounded the composition of epithelial cell subgroups of fallopian tubes and HGSOCs.
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.
Project description:Ovarian cancer is the most lethal gynecological malignancy. Recurrence and chemoresistance are tough challenges leading to poor prognosis. To further identify key genes in tumor progression, we performed RNAseq for 6 high-grade serous ovarian cancer and 5 fallopian tube and analysis of differentially expressed genes for hub genes selection.
Project description:Human mesothelial peritoneal cells from high grade serous ovarian carcinoma patients were subjected to TNFalpha, IL17-A and combination treatment.
