A Reductionist Approach Using Primary and Metastatic Cell–Derived Extracellular Vesicles Reveals Hub Proteins Associated with Oral Cancer Prognosis

Autor: Ricardo D. Coletta, Adriana Franco Paes Leme, Juliana A. Aricetti, Kelly A. Dryden, Jay W. Fox, Carolina Moretto Carnielli, Diego Mauricio Riaño-Pachón, Bianca Alves Pauletti, Rute Alves Pereira e Costa, Romênia R. Domingues, Edgard Graner, Flavia Vischi Winck, Fábio Malta de Sá Patroni, Ana Oliveira, Ariane Fidelis Busso-Lopes, Camila Caldana, Daniela C. Granato
Rok vydání: 2021
Předmět:
Proteomics
HNCDB
Head and Neck Cancer Database
HNSCC
head and neck squamous cell carcinoma
Biochemistry
Analytical Chemistry
Metastasis
Mice
AUC
area under the curve
PC
phosphatidylcholine
LMPD
LIPID MAPS Proteome Database
NTA
nanoparticle tracking analysis
Lymph node
mass spectrometry
Mouth neoplasm
0303 health sciences
lymph node metastasis
030302 biochemistry & molecular biology
Extracellular vesicle
Prognosis
Primary tumor
oral squamous cell carcinoma
medicine.anatomical_structure
Biology
PE
phosphatidylethanolamine
KEGG
Kyoto Encyclopedia of Genes and Genomes
Cell Line
Extracellular Vesicles
03 medical and health sciences
EV
extracellular vesicle
GO
Gene Ontology
microRNA
medicine
Animals
Humans
Metabolomics
OSCC
oral squamous cell carcinoma
Molecular Biology
030304 developmental biology
PCA
principal component analysis
Research
mouth neoplasms
THCA
thyroid cancer
Cancer
multi-omics
medicine.disease
Head and neck squamous-cell carcinoma
ROC
receiver operating characteristic
MicroRNAs
stomatognathic diseases
Cancer research
TCGA
The Cancer Genome Atlas
integrative analysis
PROGNÓSTICO
Zdroj: Repositório Institucional da USP (Biblioteca Digital da Produção Intelectual)
Universidade de São Paulo (USP)
instacron:USP
Molecular & Cellular Proteomics : MCP
ISSN: 1535-9476
DOI: 10.1016/j.mcpro.2021.100118
Popis: Oral squamous cell carcinoma (OSCC) has high mortality rates that are largely associated with lymph node metastasis. However, the molecular mechanisms that drive OSCC metastasis are unknown. Extracellular vesicles (EVs) are membrane-bound particles that play a role in intercellular communication and impact cancer development and progression. Thus, profiling EVs would be of great significance to decipher their role in OSCC metastasis. For that purpose, we used a reductionist approach to map the proteomic, miRNA, metabolomic, and lipidomic profiles of EVs derived from human primary tumor (SCC-9) cells and matched lymph node metastatic (LN1) cells. Distinct omics profiles were associated with the metastatic phenotype, including 670 proteins, 217 miRNAs, 26 metabolites, and 63 lipids differentially abundant between LN1 cell– and SCC-9 cell–derived EVs. A multi-omics integration identified 11 ‘hub proteins’ significantly decreased at the metastatic site compared with primary tumor–derived EVs. We confirmed the validity of these findings with analysis of data from multiple public databases and found that low abundance of seven ‘hub proteins’ in EVs from metastatic lymph nodes (ALDH7A1, CAD, CANT1, GOT1, MTHFD1, PYGB, and SARS) is correlated with reduced survival and tumor aggressiveness in patients with cancer. In summary, this multi-omics approach identified proteins transported by EVs that are associated with metastasis and which may potentially serve as prognostic markers in OSCC.
Graphical Abstract
Highlights • Proteomic, miRNA, metabolomic, and lipidomic profiles were mapped in oral cancer EVs. • The molecular profile of EVs was associated with the lymph node metastatic phenotype. • A multi-omics integrative analysis revealed 11 highly connected ‘hub proteins.’ • ‘Hub proteins’ from EVs are candidates as prognostic markers in oral cancer.
In Brief A multi-omics strategy was used to map the proteome, miRNA, metabolome, and lipidome of EVs derived from human primary tumor (SCC-9) cells and matched lymph node metastatic (LN1) cells. Differentially abundant molecules associated with the metastatic phenotype were enriched for key processes and pathways. An integrative analysis revealed 11 ‘hub proteins’ that are correlated with reduced survival and tumor aggressiveness in patients with cancer according to public databases. These EV molecules are candidates as prognostic markers in oral cancer.
Databáze: OpenAIRE
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