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Single-cell RNA-seq profiling of Pseudomyxoma Peritonei

ABSTRACT: Through single-cell transcriptomic profiling of five samples with Pseudomyxoma Peritonei (PMP) , we identified ten distinct cell type-specific clusters, including an epithelial cell community with significantly increased expression of canonical epithelial molecules, and a mesenchymal cell community with notably higher expression of established mesenchymal molecules, supporting the presence of both epithelial and mesenchymal molecular characteristics in PMP disease.

ORGANISM(S): Homo sapiens

PROVIDER: GSE228377 | GEO | 2024/10/09

REPOSITORIES: GEO

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Gene expression profiling study to identify molecular markers exhibiting distinct characteristics of Pseudomyxoma Peritonei [Fresh Frozen]

Project description:The purpose of this study is to evaluate gene expression changes and identify characteristics in patients with Pseudomyxoma Peritonei (PMP). We analyzed RNA-seq data to identify gene signatures associated with PMP development using 19 fresh frozen tissue samples including 12 PMPs (discovery cohort). Through analyzing the differences in gene expression between normal tissues and PMP, we identified statistically significant gene groups, and confirmed the biological functions and pathways associated with these gene groups.

2024-10-09 | GSE228376 | GEO

A gene expression profiling study to identify distinct molecular markers in formalin-fixed, paraffin-embedded samples of Pseudomyxoma Peritonei [FFPE]

Project description:The purpose of this study is to evaluate gene expression changes and identify characteristics in patients with Pseudomyxoma Peritonei (PMP). We analyzed RNA-seq data from 34 formalin-fixed paraffin-embedded (FFPE) samples, including 25 PMPs (validation cohort), to identify gene signatures associated with the development of PMP. We confirmed protein expression levels using a tissue microarray (TMA) cohort of PMP patients. Through analyzing the differences in gene expression between normal tissues and PMP, we identified statistically significant gene groups, and confirmed the biological functions and pathways associated with these gene groups.

2024-10-09 | GSE228375 | GEO

Global gene expression and Stromal contents improve prognostic power in PMP patients treated by CRS+HIPEC

Project description:In recent years, cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) have substantially improved the clinical outcome of pseudomyxoma peritonei (PMP) originating from mucinous appendiceal cancer. However, current histopathological grading of appendiceal PMP frequently fails in predicting disease outcome. We recently observed that the integration of cancer cell transcriptional traits with those of cancer-associated fibroblasts (CAFs) improves prognostic prediction for tumors of the large intestine. We therefore generated global expression profiles on a consecutive series of 24 PMP patients treated with CRS plus HIPEC. Multiple lesions were profiled for nine patients. We then used expression data to stratify the samples by a previously published "high-risk appendiceal cancer" (HRAC) signature and by a CAF signature that we previously developed for colorectal cancer, or by a combination of both. The prognostic value of the HRAC signature was confirmed in our cohort and further improved by integration of the CAF signature. Classification of cases profiled for multiple lesions revealed the existence of outlier samples and highlighted the need of profiling multiple PMP lesions to select representative samples for optimal performances. The integrated predictor was subsequently validated in an independent PMP cohort. These results provide new insights into PMP biology, revealing a previously unrecognized prognostic role of the stromal component and supporting integration of standard pathological grade with the HRAC and CAF transcriptional signatures to better predict disease outcome.

2021-03-21 | GSE147762 | GEO

N-glycan profiling of Pseudomyxoma peritonei

Project description:Pseudomyxoma peritonei (PMP) is a subtype of mucinous adenocarcinoma of the appendix, We compared N-linked glycan profiles of PMP tissues to those of normal appendix. N-glycosidase F liberated N-glycan profiles of eight normal appendix samples and eight low-grade and eight high-grade PMP specimens were analyzed by MALDI-TOF mass spectrometry. The most prominent alteration was increased and complex fucosylation in high-grade carcinoma. Authors: Lilli Saarinen, Pirjo Nummela, Hannele Leinonen, Annamari Heiskanen, Alexandra Thiel, Caj Haglund, Anna Lepistö, Tero Satomaa, Sampsa Hautaniemi, and Ari Ristimäki; from Genome-Scale Biology Research Program, Research Programs Unit, University of Helsinki; Glykos Finland Ltd, Helsinki; Department of Surgery, University of Helsinki and Helsinki University Hospital; Translational Cancer Biology, Research Programs Unit, University of Helsinki; and Department of Pathology, HUSLAB, University of Helsinki and Helsinki University Hospital, Finland.

2018-08-03 | PXD010086 | Pride

Exome sequencing of pseudomyxoma peritonei

Project description:Pseudomyxoma peritonei (PMP) is a subtype of mucinous adenocarcinoma mainly restricted to the peritoneal cavity and most commonly originating from the appendix. In this study, we sequenced whole coding genome of nine PMP tumors and paired normal tissues in order to identify commonly mutated genes and signaling pathways affected in PMP.

| EGAS00001002418 | EGA

Chitinophagaceae bacterium PMP191F isolate:PMP191F

Project description:Bacterial species associated with pseudomyxoma peritonei

| PRJNA290986 | ENA

Breaking the mucin barrier: a new affinity chromatography-mass spectrometry approach to unveil potential cell markers and pathways altered in Pseudomyxoma peritonei

Project description:Pseudomyxoma peritonei (PMP) is a rare, malignant tumour with unknown underlying molecular mechanisms characterised by a progressive accumulation of mucin and secreting tumour cells within the abdomen and pelvis. Cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) is the only therapeutic option currently available for its treatment and recurrence with a fatal outcome is common despite its use. The lack of information available about the molecular mechanisms underlying this condition is mainly due to the physicochemical characteristics of mucin, whose main purpose is to protect epithelial cells, which makes it inaccessible to a proteomic analysis. In this paper we describe the first protocol available to break this barrier and offer a chance to isolate proteins from soft and hard mucinous tumour tissues. This approach is based on the depletion of glycoproteins, immunoglobins, and albumins by affinity liquid chromatography, which makes the mucin available for label free quantification by mass spectrometry. As in the case of non mucinous tissues, our protocol yields a mix of total proteins and has allowed us to establish the first protein profile in mucinous tumours. In addition, our protein-protein interaction networks and pathway enrichment analyses revealed MUC13 and TFF1 as potential therapeutic targets in this disease.

2024-06-22 | PXD037364 | Pride

5349f7b2-36ff-420f-b917-b16e10af4a42 - samples

Project description:Mesothelioma of the peritoneum (n=21) and Pseudomyxoma peritonei/mucinous adenocarcinoma of the appendix (n=11)

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Glucocorticoid Regulates Mesenchymal Cell Differentiation Required for Perinatal Lung Morphogenesis and Function

Project description:We integrated genome-wide gene expression profiling, ATAC-seq, and single cell RNA-seq data in mice in which GR was deleted or activated to identify the cellular and molecular mechanisms by which glucocorticoids control prenatal lung maturation. GR activated differentiation of a newly defined proliferative mesenchymal progenitor cell (PMP) into matrix fibroblasts (MFB), in part by directly activating extracellular matrix-associated target genes, including Fn1, Col16a4, and Eln and modulating FGF, VEGF, JAK-STAT and WNT signaling. Loss of mesenchymal GR signaling blocked PMP differentiation into mature MFB, which in turn caused proliferation of SOX9+ alveolar epithelial progenitor cells and inhibited differentiation of more mature AT2 and AT1 cells. GR signaling controls genes required for differentiation of a subset of proliferative mesenchymal progenitors into matrix fibroblasts in turn, regulating signals controlling AT2/AT1 progenitor cell proliferation and differentiation, identifying cells and processes by which glucocorticoid signaling regulates fetal lung function.

2020-06-04 | GSE136954 | GEO

A Novel Assessment of Metabolic Pathways in Peritoneal Metastases from Low-Grade Appendiceal Mucinous Neoplasms

Project description:Background: There is a paucity of targeted therapies for patients with pseudomyxoma peritonei (PMP) secondary to low-grade appendiceal mucinous neoplasms (LAMNs). Dysregulated metabolism has emerged as a hallmark of cancer, and the relationship of metabolomics and cancer is an area of active scientific exploration. We sought to characterize phenotypic differences found in peritoneal metastases (PM) derived from LAMN versus adenocarcinoma. Methods: Tumors were washed with phosphate-buffered saline (PBS), microdissected, then dissociated in ice-cold methanol dried and reconstituted in pyridine. Samples were derivatized in tert-butyldimethylsilyl (TBDMS) and subjected to gas chromatography-coupled mass spectrometry. Metabolites were assessed based on a standard library. RNA sequencing was performed, with pathway and network analyses on differentially expressed genes.Results: Eight peritoneal tumor samples were obtained and analyzed: LAMNs (4), and moderate to poorly differentiated adenocarcinoma (colon [1], appendix [3]). Decreases in pyroglutamate, fumarate, and cysteine in PM from LAMNs were found compared with adenocarcinoma. Analyses showed the differential gene expression was dominated by the prevalence of metabolic pathways, particularly lipid metabolism. The gene retinol saturase (RETSAT), downregulated by LAMN, was involved in the multiple metabolic pathways that involve lipids. Using network mapping, we found IL1B signaling to be a potential top-level modulation candidate. Conclusions: Distinct metabolic signatures may exist for PM from LAMN versus adenocarcinoma. A multitude of genes are differentially regulated, many of which are involved in metabolic pathways. Additional research is needed to identify the significance and applicability of targeting metabolic pathways in the potential development of novel therapeutics for these challenging tumors.

2024-05-01 | GSE266352 | GEO

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