Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Comprehensive proteogenomic characterization of early duodenal cancer reveals the carcinogenesis tracks of different subtypes

ABSTRACT: A comprehensive proteomic and genomic analysis of 438 trace tumor samples from 156 duodenal cancers, covering all 8 major histopathology stages of 2 major and 5 rare subtypes in 23 substages via pathological dissection.

ORGANISM(S): Homo Sapiens

SUBMITTER: Chen Ding

PROVIDER: PXD038867 | iProX | Fri Dec 16 00:00:00 GMT 2022

REPOSITORIES: iProX

ACCESS DATA

Json Xml

Publications

Comprehensive proteogenomic characterization of early duodenal cancer reveals the carcinogenesis tracks of different subtypes.

Li Lingling L Jiang Dongxian D Liu Hui H Guo Chunmei C Zhao Rui R Zhang Qiao Q Xu Chen C Qin Zhaoyu Z Feng Jinwen J Liu Yang Y Wang Haixing H Chen Weijie W Zhang Xue X Li Bin B Bai Lin L Tian Sha S Tan Subei S Yu Zixiang Z Chen Lingli L Huang Jie J Zhao Jian-Yuan JY Hou Yingyong Y Ding Chen C

Nature communications 20230329 1

The subtypes of duodenal cancer (DC) are complicated and the carcinogenesis process is not well characterized. We present comprehensive characterization of 438 samples from 156 DC patients, covering 2 major and 5 rare subtypes. Proteogenomics reveals LYN amplification at the chromosome 8q gain functioned in the transmit from intraepithelial neoplasia phase to infiltration tumor phase via MAPK signaling, and illustrates the DST mutation improves mTOR signaling in the duodenal adenocarcinoma stage ...[more]

PMID: 36991000

Similar Datasets

Integrative Proteogenomic Characterization of Early Esophageal Cancer

Project description:A comprehensive proteogenomic analysis of 786 trace-tumor-samples from 154 esophageal cancers, covering all 9 major histopathology stages and 22 substages via pathological dissection.

2022-12-20 | PXD038961 |

Proteome-wide profiling of Early Colorectal Cancer

Project description:A comprehensive proteomic and genomic screening of 435 trace-tumor-samples from 148 CRC cases, covering all 10 major histopathology stages and 29 substages via pathological dissection.

2024-05-19 | PXD052391 |

Proteogenomic analysis of pancreatic cancer subtypes.

Project description:Pancreatic cancer remains a significant public health problem with an ever-rising incidence of disease. Cancers of the pancreas are characterised by various molecular aberrations, including changes in the proteomics and genomics landscape of the tumour cells. Therefore, there is a need to identify the proteomic landscape of pancreatic cancer and the specific genomic and molecular alterations associated with disease subtypes. Here, we carry out an integrative bioinformatics analysis of The Cancer Genome Atlas dataset, including proteomics and whole-exome sequencing data collected from pancreatic cancer patients. We apply unsupervised clustering on the proteomics dataset to reveal the two distinct subtypes of pancreatic cancer. Using functional and pathway analysis based on the proteomics data, we demonstrate the different molecular processes and signalling aberrations of the pancreatic cancer subtypes. In addition, we explore the clinical characteristics of these subtypes to show differences in disease outcome. Using datasets of mutations and copy number alterations, we show that various signalling pathways previously associated with pancreatic cancer are altered among both subtypes of pancreatic tumours, including the Wnt pathway, Notch pathway and PI3K-mTOR pathways. Altogether, we reveal the proteogenomic landscape of pancreatic cancer subtypes and the altered molecular processes that can be leveraged to devise more effective treatments.

| S-EPMC8432812 | biostudies-literature

scRNA-seq generates a molecular map of emerging cell subtypes after sciatic nerve injury in rats

Project description:Patients with peripheral nerve injury, viral infection or metabolic disorder often suffer neuropathic pain due to inadequate pharmacological options for relief. Developing novel therapies has been challenged by incomplete mechanistic understanding of the cellular microenvironment in sensory nerve that trigger the emergence and persistence of pain. In this study, we report a high resolution transcriptomics map of the cellular heterogeneity of naïve and injured rat sensory nerve covering more than 110,000 individual cells. Annotation reveals distinguishing molecular features of multiple major cell types totaling 45 different subtypes in naïve nerve and an additional 23 subtypes emerging after injury. Ligand-receptor analysis revealed a myriad of potential targets for pharmacological intervention. This work forms a comprehensive resource and unprecedented window into the cellular milieu underlying neuropathic pain and demonstrates that nerve injury is a dynamic process orchestrated by multiple cell types in both the endoneurial and epineurial nerve compartments.

2022-10-27 | GSE216665 | GEO

Comprehensive proteogenomic characterization of early duodenal cancer reveals the carcinogenesis tracks of different subtypes.

Project description:The subtypes of duodenal cancer (DC) are complicated and the carcinogenesis process is not well characterized. We present comprehensive characterization of 438 samples from 156 DC patients, covering 2 major and 5 rare subtypes. Proteogenomics reveals LYN amplification at the chromosome 8q gain functioned in the transmit from intraepithelial neoplasia phase to infiltration tumor phase via MAPK signaling, and illustrates the DST mutation improves mTOR signaling in the duodenal adenocarcinoma stage. Proteome-based analysis elucidates stage-specific molecular characterizations and carcinogenesis tracks, and defines the cancer-driving waves of the adenocarcinoma and Brunner's gland subtypes. The drug-targetable alanyl-tRNA synthetase (AARS1) in the high tumor mutation burden/immune infiltration is significantly enhanced in DC progression, and catalyzes the lysine-alanylation of poly-ADP-ribose polymerases (PARP1), which decreases the apoptosis of cancer cells, eventually promoting cell proliferation and tumorigenesis. We assess the proteogenomic landscape of early DC, and provide insights into the molecular features corresponding therapeutic targets.

| S-EPMC10060430 | biostudies-literature

Proteogenomic Analysis of Salivary Adenoid Cystic Carcinomas Defines Molecular Subtypes and Identifies Therapeutic Targets.

Project description:PurposeSalivary gland adenoid cystic carcinoma (ACC) has heterogeneous clinical behavior. Currently, all patients are treated uniformly, and no standard-of-care systemic therapy exists for metastatic ACC. We conducted an integrated proteogenomic analyses of ACC tumors to identify dysregulated pathways and propose a classification with therapeutic implications.Experimental designRNA/DNA sequencing of 54 flash-frozen salivary ACCs and reverse phase protein array (RPPA) in 38 specimens were performed, with validation by Western blotting and/or IHC. Three independent ACC cohorts were used for validation.ResultsBoth unbiased RNA sequencing (RNA-seq) and RPPA analysis revealed two molecular subtypes: ACC-I (37%) and ACC-II (63%). ACC-I had strong upregulation of MYC, MYC target genes, and mRNA splicing, enrichment of NOTCH-activating mutations, and dramatically worse prognosis. ACC-II exhibited upregulation of TP63 and receptor tyrosine kinases (AXL, MET, and EGFR) and less aggressive clinical course. TP63 and MYC were sufficient to assign tumors to ACC subtypes, which was validated in one independent cohort by IHC and two additional independent cohorts by RNA-seq. Furthermore, IHC staining for MYC and P63 protein levels can be used to identify ACC subtypes, enabling rapid clinical deployment to guide therapeutic decisions. Our data suggest a model in which ACC-I is driven by MYC signaling through either NOTCH mutations or direct amplification, which in turn suppress P63 signaling observed in ACC-II, producing unique therapeutic vulnerabilities for each subtype.ConclusionsCooccurrence of multiple actionable protein/pathways alterations in each subtype indicates unique therapeutic vulnerabilities and opportunities for optimal combination therapy for this understudied and heterogeneous disease.

| S-EPMC7854509 | biostudies-literature

Proteogenomic characterization of 2002 human cancers reveals pan-cancer molecular subtypes and associated pathways.

Project description:Mass-spectrometry-based proteomic data on human tumors-combined with corresponding multi-omics data-present opportunities for systematic and pan-cancer proteogenomic analyses. Here, we assemble a compendium dataset of proteomics data of 2002 primary tumors from 14 cancer types and 17 studies. Protein expression of genes broadly correlates with corresponding mRNA levels or copy number alterations (CNAs) across tumors, but with notable exceptions. Based on unsupervised clustering, tumors separate into 11 distinct proteome-based subtypes spanning multiple tissue-based cancer types. Two subtypes are enriched for brain tumors, one subtype associating with MYC, Wnt, and Hippo pathways and high CNA burden, and another subtype associating with metabolic pathways and low CNA burden. Somatic alteration of genes in a pathway associates with higher pathway activity as inferred by proteome or transcriptome data. A substantial fraction of cancers shows high MYC pathway activity without MYC copy gain but with mutations in genes with noncanonical roles in MYC. Our proteogenomics survey reveals the interplay between genome and proteome across tumor lineages.

| S-EPMC9106650 | biostudies-literature

Proteogenomic characterization of primary colorectal cancer and metastatic progression identifies proteome-based subtypes and signatures.

Project description:Metastatic progression of colorectal adenocarcinoma (CRC) remains poorly understood and poses significant challenges for treatment. To overcome these challenges, we performed multiomics analyses of primary CRC and liver metastases. Genomic alterations, such as structural variants or copy number alterations, were enriched in oncogenes and tumor suppressor genes and increased in metastases. Unsupervised mass spectrometry-based proteomics of 135 primary and 123 metastatic CRCs uncovered distinct proteomic subtypes, three each for primary and metastatic CRCs, respectively. Integrated analyses revealed that hypoxia, stemness, and immune signatures characterize these 6 subtypes. Hypoxic CRC harbors high epithelial-to-mesenchymal transition features and metabolic adaptation. CRC with a stemness signature shows high oncogenic pathway activation and alternative telomere lengthening (ALT) phenotype, especially in metastatic lesions. Tumor microenvironment analysis shows immune evasion via modulation of major histocompatibility complex (MHC) class I/II and antigen processing pathways. This study characterizes both primary and metastatic CRCs and provides a large proteogenomics dataset of metastatic progression.

| S-EPMC11288375 | biostudies-literature

Proteogenomic analysis reveals non-small cell lung cancer subtypes predicting chromosome instability, and tumor microenvironment.

Project description:Non-small cell lung cancer (NSCLC) is histologically classified into lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LSCC). However, some tumors are histologically ambiguous and other pathophysiological features or microenvironmental factors may be more prominent. Here we report integrative multiomics analyses using data for 229 patients from a Korean NSCLC cohort and 462 patients from previous multiomics studies. Histological examination reveals five molecular subtypes, one of which is a NSCLC subtype with PI3K-Akt pathway upregulation, showing a high proportion of metastasis and poor survival outcomes regardless of any specific NSCLC histology. Proliferative subtypes are present in LUAD and LSCC, which show strong associations with whole genome doubling (WGD) events. Comprehensive characterization of the immune microenvironment reveals various immune cell compositions and neoantigen loads across molecular subtypes, which predicting different prognoses. Immunological subtypes exhibit a hot tumor-enriched state and a higher efficacy of adjuvant therapy.

| S-EPMC11585665 | biostudies-literature

Proteogenomic characterization of pancreatic neuroendocrine tumors uncovers hypoxia and immune signatures in clinically aggressive subtypes.

Project description:Pancreatic neuroendocrine tumors (PanNETs) represent well-differentiated endocrine neoplasms with variable clinical outcomes. Predicting patient outcomes using the current tumor grading system is challenging. In addition, traditional systemic treatment options for PanNETs, such as somatostatin analogs or cytotoxic chemotherapies, are very limited. To address these issues, we characterized PanNETs using integrated proteogenomics and identified four subtypes. Two proteomic subtypes showed high recurrence rates, suggesting clinical aggressiveness that was missed by current classification. Hypoxia and inflammatory pathways were significantly enriched in the clinically aggressive subtypes. Detailed analyses revealed metabolic adaptation via glycolysis upregulation and oxidative phosphorylation downregulation under hypoxic conditions. Inflammatory signature analysis revealed that immunosuppressive molecules were enriched in immune hot tumors and might be immunotherapy targets. In this study, we characterized clinically aggressive proteomic subtypes of well-differentiated PanNETs and identified candidate therapeutic targets.

| S-EPMC11350455 | biostudies-literature

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