Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Quantitative tissue proteomics analysis of primary lung adenocarcinoma

ABSTRACT: In this study, we generated a quantitative lung tissue proteome dataset from lung adenocarcinoma and adjacent normal lung tissues by using iTRAQ labeling combined with 2D-LC-MS/MS. Based on pathway and network analyses, protein expression profiles released in the public Human Protein Atlas database, literature search and novelty, six candidates were selected for validation via immunohistochemistry staining and western blot. Additionally, the clinical and biological significance of two novel candidates, ERO1L and NARS, was further analyzed. Collectively, our results provide a useful biomarker dataset for lung adenocarcinoma diagnosis/prognosis and provide new insights into ERO1L- and NARS- mediated tumorigenesis.

INSTRUMENT(S): LTQ Orbitrap

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Lung, Epithelial Cell Of Lung

DISEASE(S): Lung Adenocarcinoma

SUBMITTER: Chia-Jung Yu

LAB HEAD: Chia-Jung Yu

PROVIDER: PXD004049 | Pride | 2022-03-05

REPOSITORIES: Pride

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	20100909-lungtissue-itraq-114interact.pep.xml	Pepxml
	20100909-lungtissue-itraq-114interact.prot.xml	Xml
	F1.RAW	Raw
	F10.RAW	Raw
	F11.RAW	Raw

Items per page:

1 - 5 of 62

Similar Datasets

Quantitative tissue proteomics analysis of primary lung adenocarcinoma

Project description:In this study, we generated a quantitative lung tissue proteome dataset from lung adenocarcinoma and adjacent normal lung tissues by using iTRAQ labeling combined with 2D-LC-MS/MS. Based on pathway and network analyses, protein expression profiles released in the public Human Protein Atlas database, literature search and novelty, six candidates were selected for validation via immunohistochemistry staining and western blot. Additionally, the clinical and biological significance of two novel candidates, ERO1L and NARS, was further analyzed. Collectively, our results provide a useful biomarker dataset for lung adenocarcinoma diagnosis/prognosis and provide new insights into ERO1L- and NARS- mediated tumorigenesis.

2016-05-12 | PXD004077 | Pride

TAILS proteomics of murine pancreatic tumors

Project description:Aberrant proteolysis by cysteine cathepsins is implicated in carcinogenesis, but knowledge of cathepsin substrates mediating tumor-promoting or suppressing effects is limited. Here we characterize tumor proteome and in vivo cathepsin substrates using cathepsin knockout mice and the RIP1-Tag2 model of pancreatic islet carcinogenesis. Applying an unbiased systems-level proteomics approach, Terminal Amine Isotopic Labeling of Substrates (TAILS), we identified cysteine cathepsin B, H, L, S, Z substrates and their cleavage sites. Among 1,935 proteins and 1,114 N-termini identified by TAILS using 8-plex iTRAQ protein labeling, 145 neo-N-termini were significantly changed in one (55%) or more knockouts suggesting a lack of direct compensation at substrate level by other cathepsins. Most affected N-termini (56-83% for different cathepsins) represented degradative cathepsin activity, whereas 17-44% of neo-N termini represented stable proteolytic products in the tumors and were enriched for extracellular proteins. We identified candidate substrates for mediating signaling roles of cysteine cathepsins in tumorigenesis.

2016-08-08 | PXD003637 | Pride

SILAC-iTRAQ-TAILS - Monitoring matrix metalloproteinase activity at the epidermal-dermal interface by SILAC-iTRAQ-TAILS

Project description:Secreted proteases act on interstitial tissue secretomes released from multiple cell types. Thus, substrate proteins might be part of higher molecular complexes constituted by many proteins with diverse and potentially unknown cellular origin. In cell culture these might be reconstituted by mixing native secretomes from different cell types prior to incubation with a test protease. Although current degradomics techniques could identify novel substrate proteins in these complexes, all information on the cellular origin would be lost. To address this limitation we combined iTRAQ-based Terminal Amine Isotopic Labeling of Substrates (iTRAQ-TAILS) with stable isotope labeling by amino acids in cell culture (SILAC) to assign proteins to a specific cell type by MS1- and their cleavage by MS2-based quantification in the same experiment. We demonstrate the power of our newly established workflow by monitoring matrix metalloproteinase (MMP) 10-dependent cleavages in mixtures from heavy labeled fibroblast and light labeled keratinocyte sectretomes. This analysis correctly assigned extracellular matrix components, such as laminins and collagens, to their respective cellular origins and revealed their processing in an MMP10-dependent manner. Hence, our newly devised degradomics workflow facilitates deeper insights into protease activity in complex intercellular compartments like the epidermal-dermal interface by integrating multiple modes of quantification with positional proteomics.

2015-05-11 | PXD001643 | Pride

LKB1 drives stasis and C/EBP-mediated reprogramming to an alveolar type II fate in lung cancer

Project description:LKB1 is among the most frequently altered tumor suppressors in lung adenocarcinoma. Inactivation of Lkb1 accelerates the growth and progression of oncogenic KRAS-driven lung tumors in mouse models. However, the molecular mechanisms by which LKB1 constrains lung tumorigenesis and whether the aggressive cancer state that stems from Lkb1 deficiency can be reverted remains unknown. To identify the processes governed by LKB1 in vivo, we generated an allele which enables Lkb1 inactivation during tumor development and subsequent Lkb1 restoration in established tumors. Restoration of Lkb1 in oncogenic KRAS-driven lung tumors suppressed proliferation and promoted tumor stasis. Lkb1 restoration activated targets of C/EBP transcription factors and drove the transition of neoplastic cells from a progenitor-like state to a less proliferative alveolar type II cell-like state. We show that C/EBP transcription factors govern a subset of genes that are induced by LKB1 and depend upon NKX2-1. We also demonstrate that a defining factor of the alveolar type II lineage, C/EBPα, constrains oncogenic KRAS-driven lung tumor growth. Thus, we uncover a role for a critical tumor suppressor in the regulation of key lineage-specific transcription factors, thereby constraining lung tumor development through the enforcement of differentiation.

2021-12-23 | PXD026738 | Pride

29RNP kinase idetification - Identification and characterization of chloroplast casein kinase II from Oryza sativa (rice)

Project description:The 29-kDa RNA protein (29RNP), which was originally identified in rice etioplasts, has increased phosphorylation levels during de-etiolation. Here, using heparin-sepharose enriched fractions, we identified a chloroplast kinase that phosphorylated 29RNP. The chloroplast kinase phosphorylated the 29RNP and exhibited CKII biochemical characteristics in a kinase reaction test. Proteomic analysis of the chloroplast heparin-sepharose enriched fractions revealed the presence of 70 proteins, including both abundant proteins, such as plastid encoded polymerase subunits, and low-abundance proteins, such as APO2 and DAG. An inclusion list method using Fourier transform ion cyclotron resonance mass spectrometer ( FT-ICR LTQ MS ) was subsequently used to analyze the chloroplast heparin-sepharose enriched fractions. The 29RNP kinase was positively identified as a CKII alpha family protein by the presence of two unique peptides.

2015-04-27 | PXD000951 | Pride

Ito2019 - gefitnib resistance of lung adenocarcinoma caused by MET amplification

Project description:The model is based on publication: Mathematical analysis of gefitinib resistance of lung adenocarcinoma caused by MET amplification Abstract: Gefitinib, one of the tyrosine kinase inhibitors of epidermal growth factor receptor (EGFR), is effective for treating lung adenocarcinoma harboring EGFR mutation; but later, most cases acquire a resistance to gefitinib. One of the mechanisms conferring gefitinib resistance to lung adenocarcinoma is the amplification of the MET gene, which is observed in 5–22% of gefitinib-resistant tumors. A previous study suggested that MET amplification could cause gefitinib resistance by driving ErbB3-dependent activation of the PI3K pathway. In this study, we built a mathematical model of gefitinib resistance caused by MET amplification using lung adenocarcinoma HCC827-GR (gefitinib resistant) cells. The molecular reactions involved in gefitinib resistance consisted of dimerization and phosphorylation of three molecules, EGFR, ErbB3, and MET were described by a series of ordinary differential equations. To perform a computer simulation, we quantified each molecule on the cell surface using flow cytometry and estimated unknown parameters by dimensional analysis. Our simulation showed that the number of active ErbB3 molecules is around a hundred-fold smaller than that of active MET molecules. Limited contribution of ErbB3 in gefitinib resistance by MET amplification is also demonstrated using HCC827-GR cells in culture experiments. Our mathematical model provides a quantitative understanding of the molecular reactions underlying drug resistance.

2024-09-02 | BIOMD0000000827 | BioModels

BMP1/Tolloid-like substrates by iTRAQ degradomics

Project description:In this study, we used an iTRAQ-based quantitative proteomic approach to reveal the release of proteolytic fragments from the cell surface or the ECM by BMP-1. Thirty-seven extracellular proteins were found in significantly higher or lower amounts in the conditioned medium of HT1080 cells overexpressing BMP-1 and thus, could be considered as candidate substrates. Strikingly, three of these new candidates (betaglycan, CD109 and neuropilin-1) were TGF-Beta co-receptors, also acting as antagonists when released from the cell surface, and were chosen for further substrate validation.

2014-09-29 | PXD000786 | Pride

Characterizing the secretome of EGFR mutant lung adenocarcinoma

Project description:Lung cancer is the leading cause of cancer related death worldwide, mainly due to the late stage of disease at the time of diagnosis. Non-invasive biomarkers are needed to supplement existing screening methods to enable earlier detection and increased patient survival. This is critical to EGFR-driven lung adenocarcinoma as it commonly occurs in individuals who have never smoked and do not qualify for current screening protocols. Methods: In this study, we performed mass spectrometry analysis of the secretome of cultured lung cells representing different stages of mutant EGFR driven transformation, from normal to fully malignant. Identified secreted proteins specific to the malignant state were validated using orthogonal methods and their clinical activity assessed in lung adenocarcinoma patient cohorts. Results: We quantified 1020 secreted proteins, which were compared for differential expression between stages of transformation. We validated differentially expressed proteins at the transcriptional level in clinical tumor specimens, association with patient survival, and absolute concentration to yield three biomarker candidates: MDK, GDF15, and SPINT2. These candidates were validated using ELISA and increased levels were associated with poor patient survival specifically in EGFR mutant lung adenocarcinoma patients. Conclusions: Our study provides insight into changes in secreted proteins during EGFR driven lung adenocarcinoma transformation that may play a role in the processes that promote tumor progression. The specific candidates identified can harnessed for biomarker use to identify high risk individuals for early detection screening programs and disease management for this molecular subgroup of lung adenocarcinoma patients.

2024-01-03 | PXD045328 | Pride

Mouse liver LC-MS/MS - The influence of AICAR - direct activator of AMP-activated protein kinase (AMPK) - on liver proteome in apoE-knockout mice

Project description:Shotgun LC-MS/MS on mitochondrial and cytosolic fraction of the liver of apoE-knockout mice

2017-05-02 | PXD002615 | Pride

Mycobacterium tuberculosis extracellular vesicle proteome

Project description:Tuberculosis is a common infectious disease mostly caused by Mycobacterium tuberculosis. M. tuberculosis have been shown to release extracellular vesicles (EVs) containing immunologically active molecules. However, only limited number of proteins has been identified in M. tuberculosis EVs. We present a comprehensive proteome of M. tuberculosis EVs to elucidate the pathogenesis of M. tuberculosis EVs and suggest several potential biomarker candidates.

2015-07-30 | PXD001160 | Pride

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