Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Proteogenomic Landscape of Uterine Leiomyomas from Hereditary Leiomyomatosis and Renal Cell Cancer Patients

ABSTRACT: Pathogenic mutations in fumarate hydratase (FH) drive hereditary leiomyomatosis and renal cell cancer (HLRCC) and increase the risk of developing uterine leiomyomas (ULMs). An integrated proteogenomic analysis of ULMs from HLRCC (n=16; FH-mutation confirmed) and non-syndromic (NS) patients (n=12) identified a significantly higher protein:transcript correlation in HLRCC (R=0.35) vs. NS ULMs (R=0.242, MWU p=0.0015). Co-altered proteins and transcripts (228) included antioxidant response element (ARE) target genes, such as thioredoxin reductase 1 (TXNRD1), and correlated with activation of NRF2-mediated oxidative stress response signaling in HLRCC ULMs. We confirm 185 transcripts previously described as altered between HLRCC and NS ULMs, 51 co-altered at the protein level and several elevated in HLRCC ULMs are involved in regulating cellular metabolism and glycolysis signaling. Furthermore, 367 S-(2-succino)cysteine peptides were identified in HLRCC ULMs, of which sixty were significantly elevated in HLRCC vs. NS ULMs (LogFC=1.86, MWU p<0.0001). These results confirm and define novel proteogenomic alterations in uterine leiomyoma tissues collected from HLRCC patients and underscore conserved molecular alterations correlating with inactivation of the FH tumor suppressor gene.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Liver, Uterine Leiomyoma Cell

DISEASE(S): Leiomyomatosis,Renal Cell Carcinoma

SUBMITTER: Brian Hood

LAB HEAD: Thomas P Conrads, PhD

PROVIDER: PXD024830 | Pride | 2021-12-15

REPOSITORIES: Pride

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	Fibroid_TMT10_R1_01a.raw	Raw
	Fibroid_TMT10_R1_01a_PSMs.txt	Txt
	Fibroid_TMT10_R1_01b.raw	Raw
	Fibroid_TMT10_R1_02a.raw	Raw
	Fibroid_TMT10_R1_02b.raw	Raw

Items per page:

1 - 5 of 139

Similar Datasets

Peptide Ancestry Informative Markers in Uterine Neoplasms from Women of European, African and Asian Ancestry

Project description:Characterization of ancestry-linked peptide variants in disease-relevant patient tissues represents a foundational step to connect patient ancestry with molecular disease pathogenesis. Nonsynonymous single nucleotide polymorphisms (SNPs) encoding missense substitutions within tryptic peptides exhibiting high allele frequencies in European, African, and East Asian populations, termed peptide ancestry informative markers (pAIMs), were prioritized from 1000 genomes. In silico analysis shows that as few as 20 pAIMs can determine ancestry proportions similarly to >260K SNPs (R2=0.9905). Multiplexed proteomic analysis of >100 human endometrial cancer cell lines and uterine leiomyoma (ULM) tissues combined resulted in the quantitation of 62 pAIMs that correlate with self-described race and genotype-confirmed patient ancestry. Candidates include a D451E substitution in GC vitamin D-binding protein previously associated with altered vitamin D levels in African and European populations. These efforts describe a generalized set of markers for proteoancestry assessment that will further support studies investigating the impact of ancestry on the human proteome and how this relates to the pathogenesis of uterine neoplasms.

2022-02-16 | PXD029323 | Pride

Proteogenomic analysis of lung adenocarcinoma reveals tumor heterogeneity, survival determinants and therapeutically-relevant pathways

Project description:To characterize the etiology of lung adenocarcinoma (LUAD) in the United States, we performed deep proteogenomic profiling of 87 tumors integrating whole genome sequencing, transcriptome sequencing, proteomics and phosphoproteomics by mass spectrometry and reverse phase protein arrays. Somatic genome signature analysis revealed three subtypes including a structurally altered subtype enriched with former smokers, genomic inversions and deletions and TP53 alteration, a transition-high subtype enriched with never-smokers, and a transversion-high enriched with current smokers. We discovered that within-tumor correlations of RNA expression and protein expression were associated with tumor purity, grade, immune cell heterogeneity, and expression subtype. We detected and independently validated RNA and protein expression signatures predicting patient survival. A greater number of proteins than RNA transcripts had association with patient survival. Integrative analysis characterized three expression subtypes with divergent mutations, proteomic regulatory networks and therapeutic vulnerabilities. This proteogenomic characterization provides a new foundation for molecularly-informed medicine in LUAD.

2022-11-16 | PXD036025 | Pride

Evaluation of Tumor Infiltrating Lymphocytes in High-Grade Serous Ovarian Cancer

Project description:Tumor infiltrating lymphocytes (TILs) play a significant role in the tumor microenvironment in high-grade serous ovarian cancer (HGSOC). To better understand the interactions and functions of TILs in HGSOC progression, we performed proteogenomic profiling of TILs in 65 tumors collected from 12 HGSOC patients.

2024-03-15 | PXD045710 | Pride

Proteogenomic Analysis of Enriched Tumor Epithelium Identifies Prognostic Signatures and an Increased Dependency of Homologous Recombination Proficient Cells on BMI1 in High Grade Serous Ovarian Cancer

Project description:Although several proteogenomic analyses of high-grade serous ovarian cancer (HGSOC) have been conducted, these analyses are often dominated by tissues with high levels of tumor cell nuclei (purity), despite low purity being associated with worse outcome. We performed deep proteogenomic profiling of bulk tumor (BT) and laser microdissection (LMD) enriched tumor (ET) and stromal (ST) cell populations from 70 HGSOC patient tumors spanning a broad spectrum of purity. We identified a cluster of patients with longer progression free survival associated with increased immune signatures and validated proteins correlating with tumor infiltrating lymphocytes (TILs) in 65 tumors collected from an independent cohort of 12 HGSOC patients, as well as with overall survival in an additional cohort of 126 HGSOC patients. We identified that homologous recombination deficient (HRD) tumors express transcriptomic and proteomic pathways associated with metabolism and oxidative phosphorylation that we validated in independent patient cohorts, including 69 HRD-positive HGSOC tumors. In summary, our proteogenomic analysis provides important new clinically relevant insights into HGSOC tumor cell populations, and have uncovered prognostic proteogenomic alterations correlating with TILs, low tumor purity, as well as expression alterations associated with HRD status and immune infiltration.

2024-03-15 | PXD045417 | Pride

The effect of FH mutations on fibroid expression profile, normal myometrium vs. FH-mutant fibroids.

Project description:A series of gene expression measurements of uterine fibroids with mutated fumarate hydratase (FH) gene and normal myometrium. Keywords: other

2005-12-20 | GSE2724 | GEO

The effect of FH mutations on fibroid expression profile

Project description:A series of gene expression measurements of uterine fibroids with mutated or wild-type fumarate hydratase (FH) gene. Keywords: other

2005-12-20 | GSE2152 | GEO

Transcription profiling of human uterine fibroids with mutated or wild type fumarate hydratase gene

Project description:A series of gene expression measurements of uterine fibroids with mutated or wild-type fumarate hydratase (FH) gene.

2007-08-25 | E-GEOD-2152 | biostudies-arrayexpress

The effect of FH mutations on fibroid expression profile 2.

Project description:A series of gene expression measurements of normal myometrium and uterine fibroids with mutated or wild-type fumarate hydratase (FH) gene. Keywords: other

2005-12-20 | GSE2725 | GEO

Transcription profiling of human fibriods vs. normal myometrium with mutated or wild type fumarate hydratase (FH) gene reveals distinct expression profiles in fumarate-hydratase-deficient uterine fibroids.

Project description:A series of gene expression measurements of normal myometrium and uterine fibroids with mutated or wild-type fumarate hydratase (FH) gene.

2007-10-02 | E-GEOD-2725 | biostudies-arrayexpress

Transcription profiling of human uterine fibroids and normal myometrium

Project description:Defects in mitochondrial enzymes predispose to severe developmental defects as well as tumorigenesis. Heterozygous germline mutations in the nuclear gene encoding fumarate hydratase (FH), an enzyme catalyzing the hydration of fumarate in the Krebs tricarboxylic acid cycle, cause hereditary leiomyomatosis and renal cell cancer; yet the connection between disruption of mitochondrial metabolic pathways and neoplasia remains to be discovered. We have used an expression microarray approach for studying differences in global gene expression pattern caused by mutations in FH. Seven uterine fibroids carrying FH mutations were compared with 15 fibroids with wild-type FH. The two groups showed markedly different expression profiles, and multiple differentially expressed genes were detected. The most significant increase in FH mutants was seen in the expression of carbohydrate metabolism- and glycolysis-related genes. Other significantly up-regulated gene categories in FH mutants were, for example, iron ion homeostasis and oxidoreduction. Genes with lower expression in FH-mutant fibroids belonged to groups such as extracellular matrix, cell adhesion, muscle development and cell contraction. We show that FH mutations alter significantly the expression profiles of fibroids, most strikingly increasing the expression of genes involved in glycolysis.

2007-10-02 | E-GEOD-2724 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data