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

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

PROVIDER: PRJNA1106805 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR28863233_1.fastq.gz	Fastqsanger.gz
	SRR28863233_2.fastq.gz	Fastqsanger.gz
	SRR28863234_1.fastq.gz	Fastqsanger.gz
	SRR28863234_2.fastq.gz	Fastqsanger.gz
	SRR28863235_1.fastq.gz	Fastqsanger.gz

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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

Gene expression profile of microdissected mucinous cystic neoplasms of the pancreas

Project description:Gene expression profile of laser-capture microdissected epithelium component of 6 mucinous cystic neoplasms of the pancreas were included in the study. The expression arrays were generated with Affymetrix HU133A gene chips (18,462 genes/EST transcripts).

2018-06-28 | E-MTAB-6853 | biostudies-arrayexpress

Improved Detection of Circulating Epithelial Cells in Patients with Intraductal Papillary Mucinous Neoplasms

Project description:Circulating epithelial cells (CECs) were purified using a microfluidic device from healthy donors, patients bearing intraductal papillary mucinous neoplasms, or pancreatic ductal adenocarcinoma and their transcriptomes were sequenced.

2017-11-01 | GSE103152 | GEO

Outcomes of Low-Grade Appendiceal Mucinous Neoplasms with Remote Acellular Mucinous Peritoneal Deposits.

Project description:BACKGROUND:Occasionally, low-grade appendiceal mucinous neoplasms (LAMN) present with mucinous peritoneal deposits (MPD) localized to periappendiceal tissue or diffused throughout the peritoneum. OBJECTIVE:This study was aimed at evaluating the relevance of mucin cellularity for predicting outcomes of LAMN with remote MPD. METHODS:The records of patients with LAMN and remote MPD who underwent initial assessment at a comprehensive cancer center from 1990 to 2015 were reviewed, and diagnostic procedures, treatments, and outcomes were analyzed. RESULTS:Of 48 patients included in the analysis, 19 had cellular MPD (CMPD) and 29 had acellular MPD. Of 33 patients who underwent cytoreductive surgery, 30 had a complete cytoreduction; the 3 patients with an incomplete cytoreduction had CMPD. In the follow-up period (median, 4 years), 6 patients died of the disease, all of whom had CMPD. Of 11 patients who had progression of disease, 10 had CMPD. CONCLUSION:Cellularity of remote MPD is an important determinant of disease outcome in LAMN. Approaches such as active surveillance may have a role in selected patients with LAMN and AMPD.

| S-EPMC6339600 | biostudies-literature

Quantitative Proteomic Profiling for Predicting Grade of Dysplasia in Intraductal Papillary Mucinous Neoplasm using Pancreatic Cyst Fluid

Project description:The increased number of pancreatic cyst lesions (PCLs) have been detected through the development of abdominal imaging techniques, such as computed tomography (CT), magnetic resonance imaging (MRI), and endoscopic ultrasound (EUS). However, accurate classification of cystic lesions is difficult because of the lack of standardized diagnostic methods, and thus potentially unnecessary surgical resection has been performed on pancreatic cyst patients. Among four most common types of cystic lesions of pancreas, intraductal papillary mucinous neoplasms (IPMNs), mucinous cystic neoplasms (MCN), serous cystic neoplasms (SCN), and solid pseudopapillary neoplasms (SPNs), IPMNs, the precursor lesion of pancreatic cancer, have been detected most frequently, and are subdivided into low-grade dysplasia (LGD), high-grade dysplasia (HGD), and invasive IPMN in accordance with their malignancy. To discover the potential biomarkers of the histological grades of IPMN, we investigated pancreatic cyst fluid proteins that are differentially expressed in accordance with the IPMN malignancy by LC-MS/MS analysis.

2020-09-06 | PXD016127 | Pride

Quantitative Proteomic Analysis of Pancreatic Cyst Fluid Proteins Associated with Malignancy in Intraductal Papillary Mucinous Neoplasms

Project description:Intraductal papillary mucinous neoplasm (IPMN) is a benign tumor that grows within the pancreatic ducts characterized by the production of thick mucinous fluid by surrounding tumor cells. IPMN is the most important precursor lesion for pancreatic cancer that is the fourth most common cause of cancer deaths. Differentiating between low-grade dysplasia (LGD), high-grade dysplasia (HGD), and invasive intraductal papillary mucinous neoplasms (IPMNs) remains a diagnostic challenge with current biomarkers, necessitating the development of novel biomarkers that can distinguish IPMN malignancy. We investigated differentially expressed proteins among pancreatic cyst fluids consisted of LGD, HGD, and invasive IPMN patients by using our novel proteomic strategy, and finally we discovered pancreatic cyst fluid protein marker candidates that can predict the malignant potential of IPMNs.

2018-05-01 | PXD008302 | Pride

Neoadjuvant chemotherapy modulates T cell responses in high-grade serous ovarian cancer metastases

2016-07-27 | GSE71340 | GEO

Neoadjuvant chemotherapy modulates T cell responses in high-grade serous ovarian cancer metastases

Project description:Our data suggest that neoadjuvant chemotherapy enhances anti-cancer responses of T cells in peritoneal metastases of patients with high-grade serous ovarian cancer but does not decrease levels of immune checkpoint molecules, providing a rationale for sequential chemo-immunotherapy. tRNA was isolated from 35 omental tissue samples of HGSOC metastases either pre or post NACT treatment. RNASeq was performed on poly-A selected mRNA fragments, 100 b.p paired end, and strand specific, on average 40 million reads per sample.

2016-07-27 | E-GEOD-71340 | biostudies-arrayexpress

Frequent GNAS mutations in low-grade appendiceal mucinous neoplasms.

Project description:The molecular basis for the development of appendiceal mucinous tumours, which can be a cause of pseudomyxoma peritonei, remains largely unknown.Thirty-five appendiceal mucinous neoplasms were analysed for GNAS and KRAS mutations. A functional analysis of mutant GNAS was performed using a colorectal cancer cell line.A mutational analysis identified activating GNAS mutations in 16 of 32 low-grade appendiceal mucinous neoplasms (LAMNs) but in none of three mucinous adenocarcinomas (MACs). KRAS mutations were found in 30 LAMNs and in all MACs. We additionally analysed a total of 186 extra-appendiceal mucinous tumours and found that GNAS mutations were highly prevalent in intraductal papillary mucinous tumours of the pancreas (88%) but were rare or absent in mucinous tumours of the colorectum, ovary, lung and breast (0-9%). The prevalence of KRAS mutations was quite variable among the tumours. The introduction of the mutant GNAS into a colorectal cancer cell line markedly induced MUC2 and MUC5AC expression, but did not promote cell growth either in vitro or in vivo.Activating GNAS mutations are a frequent and characteristic genetic abnormality of LAMN. Mutant GNAS might play a direct role in the prominent mucin production that is a hallmark of LAMN.

| S-EPMC3590682 | biostudies-other

Integrated characterization of cell types, states and molecular programs in disseinated appendiceal neoplasms

Project description:Appendiceal neoplasms include a heterogeneous group of epithelial and non-epithelial tumors with varying malignant potential. Despite the rise in incidence of appendiceal neoplasms in recent years, limited progress has been made in the understanding, management and therapeutic treatment. To comprehensively characterize the cell types and molecular mechanisms driving cellular remodeling in epithelial appendiceal neoplasms, we performed an integrated scRNA-seq study. We analyzed 126,998 cells from 16 appendix samples (11 peritoneal metastases samples, 5 healthy controls) and identified 33 distinct cell types/cell states with seven being cancer-specific. Highlights of our study include the characterization of tumor cells across the histologic spectrum, the identification of a novel cancer-associated-fibroblast (CAF) subtypes (fiCAFs) and the identification of pathologic-specific cellular crosstalks between tumor cells and the tumor microenvironment (TME). Together, our study provides a high-resolution insight into the complexity and heterogeneity of epithelial appendiceal neoplasms and a valuable resource for therapeutic strategies.

2023-10-04 | GSE244031 | GEO

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