Longitudinal single-cell RNA-seq data of metastatic ovarian cancer
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ABSTRACT:
PROVIDER: EGAS00001005010 | EGA |
REPOSITORIES: EGA
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Project description:We characterized transcriptional patterns of chemotherapy resistance in high-grade serous ovarian cancer (HGSOC) using patient-derived prospective tissue sample pairs before and after treatment at single-cell resolution. Our cohort consists of scRNA-seq data from treatment-naïve and post-neoadjuvant chemotherapy (post-NACT) pairs from 11 homogeneously treated HGSOC patients. After quality control, we obtained 51,786 cells, including 8,806 malignant epithelial (tumor), 8,045 stromal and 34,935 immune cells. Our unbiased analysis reveals how chemotherapy modulates cancer cell states by both subclonal selection and microenvironment boosted transcriptional induction across the homogeneously treated sample cohort. Our results define a cell state that allows biomarker-based prediction and targeting of chemoresistance.
2021-12-24 | GSE165897 | GEO
Project description:Despite the similar histologic appearances of high-grade serous ovarian cancers (HGSOCs), clinical observations point to marked differences in their gross appearances. Some patients have numerous small nodules, whereas others have bulkier disease; some patients have widespread disease, whereas others have more localized disease. However, a systematic framework for classifying such gross morphologic differences does not exist. The implementation of a laparoscopic triage algorithm for patients with advanced HGSOC enabled us to prospectively obtain detailed video images of HGSOC that could be analyzed to identify morphologic subtypes. In this study, we aimed to develop and characterize a gross morphologic classification system for HGSOC. Specifically, we assessed whether HGSOC can be reliably divided into distinct gross morphologic subtypes and whether such subtypes have different clinical outcomes and molecular features.
2023-01-27 | PXD031518 | Pride
Project description:Purpose: Most molecular characterizations of high-grade serous ovarian cancer (HGSOC) have been done in primary ovarian tumors. Such data may not be fully representative of HGSOC, which is characterized by widespread peritoneal metastases at the time of diagnosis and upon relapse. The most common site of HGSOC metastasis is the omentum. The omentum is characterized by strong immune and fibrotic activities and is a rich source of mesenchymal stem cells (MSCs), which have the capacity to differentiate into cancer-associated fibroblasts (CAFs) and promote ovarian cancer progression. The omentum is also rich in tertiary lymphoid structures (TLS), which are transient aggregates of leukocytes structurally and functionally comparable to secondary lymphoid tissues. Experimental design: With the goal of elucidating expression patterns in a large number of omental metastases, we profiled expression of immune- and cancer progression-related genes in pretreatment omental metastasis samples from 152 patients diagnosed with HGSOC.
2020-07-02 | GSE135712 | GEO
Project description:Longitudinal single-cell RNA-seq data of prospectively collected tumor tissue samples before and after chemotherapy from 11 HGSOC patients.
| EGAD00001006922 | EGA
Project description:In metastatic cancer, the degree of heterogeneity of the tumor-immune microenvironment and its molecular underpinnings remain largely unstudied. To characterize the tumor-immune interface at baseline and during neoadjuvant chemotherapy in high-grade serous ovarian cancer (HGSOC), we performed immunogenomics analysis of treatment-naive and paired pre/post-chemotherapy treated samples. In treatment-naive HGSOC, we find that immune cell-excluded and inflammatory microenvironments co-exist within the same individuals and within the same tumor sites, indicating ubiquitous variability in immune cell infiltration. Analysis of tumor microenvironment cell composition, DNA copy number, mutations and gene expression showed that immune cell exclusion was associated with amplification of Myc target genes and increased expression of canonical Wnt signaling in treatment-naive HGSOC. Following neoadjuvant chemotherapy, increased natural killer cell infiltration and oligoclonal expansion of T cells were detected. We demonstrate that the tumor-immune microenvironment of advanced HGSOC is intrinsically heterogeneous and that chemotherapy induces local immune activation, suggesting that chemotherapy can potentiate the immunogenicity of immune-excluded HGSOC tumors. The goal of this particular experiment was quantify RNA expression using microarray technology, and then evaluate differences in the trasncirptomic landscape of treatment naïve metastatic high grade serous ovarian cancer.
2020-03-14 | GSE146964 | GEO
Project description:In metastatic cancer, the degree of heterogeneity of the tumor-immune microenvironment and its molecular underpinnings remain largely unstudied. To characterize the tumor-immune interface at baseline and during neoadjuvant chemotherapy in high-grade serous ovarian cancer (HGSOC), we performed immunogenomics analysis of treatment-naive and paired pre/post-chemotherapy treated samples. In treatment-naive HGSOC, we find that immune cell-excluded and inflammatory microenvironments co-exist within the same individuals and within the same tumor sites, indicating ubiquitous variability in immune cell infiltration. Analysis of tumor microenvironment cell composition, DNA copy number, mutations and gene expression showed that immune cell exclusion was associated with amplification of Myc target genes and increased expression of canonical Wnt signaling in treatment-naive HGSOC. Following neoadjuvant chemotherapy, increased natural killer cell infiltration and oligoclonal expansion of T cells were detected. We demonstrate that the tumor-immune microenvironment of advanced HGSOC is intrinsically heterogeneous and that chemotherapy induces local immune activation, suggesting that chemotherapy can potentiate the immunogenicity of immune-excluded HGSOC tumors. The goal of this particular experiment was quantify RNA expression using microarray technology, and then evaluate differences in the trasncirptomic landscape of treatment naïve metastatic high grade serous ovarian cancer.
2020-03-14 | GSE146963 | GEO
Project description:High-grade serous ovarian cancer (HGSOC) exhibits significant genomic heterogeneity within a patient at presentation. Recent work has suggested that this heterogeneity is linked to the development of resistance and disease progression in that chemotherapy selects for minor resistant subclones embodied in presentation disease leading to short progression-free survival and resistant relapse. Cell line models support this by showing that relapse is not an immediate descendant of presentation disease, but so far no immediate clinical evidence has been provided that convincingly demonstrates the origin of relapse. It is further still unclear what evolutionary processes shape the mutational landscape of HGSOC in vivo and to what extent the degree of genomic heterogeneity impacts a patient's clinical outcome. We address these questions by inferring evolutionary trees of metastatic disease from structural variations between 138 cancer samples obtained from 17 patients undergoing neoadjuvant chemotherapy for HGSOC. Using novel phylogenetic methods, we quantify genomic changes in the course of chemotherapy and the degree of clonal expansion and show that these indices determine patient outcome with high accuracy. We demonstrate that relapse is indeed a minor subclone of presentation disease by verifying that the focal NF1 deletion of a relapse case was already present at biopsy. By leveraging the information contained in the evolutionary trees, we unveil the etiology of genetic heterogeneity and the tumorigenic potential of HGSOC cell populations. This is the first comprehensive study showing the origin, strength and effect of genetic heterogeneity in HGSOC in a clinical setting. In addition to its immediate clinical significance, it strengthens previous statements that single sample biopsies are seemingly insufficient to predict disease progression and stresses the importance of establishing multiple sampling as a routine approach in the clinic. Clinical data and tissue samples were collected on the prospective CTCR-OV03 and CTCR-OV04 clinical studies designed to identify biomarkers of heterogeneity.
2014-10-01 | E-GEOD-40546 | biostudies-arrayexpress
Project description:Optimal cytoreduction to no residual disease (R0) correlates with improved disease outcome in the management of high-grade serous ovarian cancer (HGSOC) patients. Neoadjuvant chemotherapy (NACT) followed by interval debulking surgery (IDS) offers an alternate approach to management of HGSOC patients to achieve complete resection. This study assessed proteomic alterations in matched, chemotherapy naïve and NACT-treated patients tumors obtained from HGSOC patients with suboptimal (R1) versus optimal (R0) debulking at IDS. We describe distinct proteome profiles in pre- and post-NACT HGSOC tumors correlating with residual disease status providing prognostic biomarkers for residual disease at IDS as well as candidate proteins associated with NACT resistance warranting further pre-clinical investigation.
2022-10-05 | PXD031929 | Pride
Project description:While high-grade serous ovarian carcinoma (HGSOC) is the most common histological subtype of ovarian cancer, significant tumor heterogeneity exists. In addition, chemotherapy induces changes in gene expression and alters the mutational profile. To evaluate the notion that patients with HGSOC could be better classified for optimal treatment based on gene expression, we compared genetic variants (by DNA next-generation sequencing [NGS] using a 50 gene Ion Torrent panel) and gene expression (using the NanoString® PanCancer 770 gene Panel) in the tumor from 20 patients with HGSOC before and after neoadjuvant chemotherapy (NACT). NGS was performed on plasma cell free DNA (cfDNA) on a select group of patients (n=14) in order to assess the utility of using cfDNA to monitor these changes. A total of 86 genes had significant changes in RNA expression after NACT. Thirty-eight genetic variants (including SNPs) from 6 genes were identified in tumors pre-NACT, while 59 variants from 19 genes were detected in the cfDNA. The number of DNA variants were similar after NACT. Of the 59 variants in the plasma pre-NACT, only 6 persisted; whereas 33 of 38 specific variants in the tumor DNA remained unchanged. Pathway analysis showed the most significant alterations in the cell cycle and DNA damage pathways.
2018-02-01 | GSE109934 | GEO
Project description:Cancer recurrence and chemoresistance are the leading causes of death in high-grade serous ovarian cancer (HGSOC) patients. However, the unique role of the immune environment in tumor progression for relapsed chemo-resistant patients remains elusive. In single-cell resolution, we characterized a comprehensive multi-dimensional cellular and immunological atlas from tumor, ascites, and peripheral blood of a chemo-resistant patient at different stages of treatment. Our results highlight a role in recurrence and chemoresistance of the immunosuppressive microenvironment in ascites, including MDSC-like myeloid and hypo-metabolic γδT cells, and of peripheral CD8+ effector T cells with chemotherapy-induced senescent/exhaustive. Importantly, paired TCR/BCR sequencing demonstrated relative conservation of TCR clonal expansion in hyper-expanded CD8+ T cells and extensive BCR clonal expansion without usage bias of V(D)J genes after chemotherapy. Thus, our study suggests strategies for ameliorating chemotherapy-induced immune impairment to improve the clinical outcome of HGSOC.
2022-09-15 | GSE213243 | GEO