SWATH-MS based proteomic profiling of pancreatic ductal adenocarcinoma tumours reveals the interplay between the extracellular matrix and related intracellular pathways.
Aged
Aged, 80 and over
Biomarkers, Tumor
/ genetics
Carcinoma, Pancreatic Ductal
/ genetics
Case-Control Studies
Cohort Studies
Extracellular Matrix
/ metabolism
Female
Follow-Up Studies
Gene Expression Profiling
Gene Expression Regulation, Neoplastic
Gene Regulatory Networks
Humans
Male
Mass Spectrometry
Middle Aged
Pancreatic Neoplasms
/ genetics
Polymorphism, Single Nucleotide
Prognosis
Proteome
/ analysis
Journal
PloS one
ISSN: 1932-6203
Titre abrégé: PLoS One
Pays: United States
ID NLM: 101285081
Informations de publication
Date de publication:
2020
2020
Historique:
received:
11
06
2020
accepted:
27
09
2020
entrez:
13
10
2020
pubmed:
14
10
2020
medline:
15
12
2020
Statut:
epublish
Résumé
Pancreatic cancer accounts for 2.8% of new cancer cases worldwide and is projected to become the second leading cause of cancer-related deaths by 2030. Patients of African ancestry appear to be at an increased risk for pancreatic ductal adenocarcinoma (PDAC), with more severe disease and outcomes. The purpose of this study was to map the proteomic and genomic landscape of a cohort of PDAC patients of African ancestry. Thirty tissues (15 tumours and 15 normal adjacent tissues) were obtained from consenting South African PDAC patients. Optimisation of the sample preparation method allowed for the simultaneous extraction of high-purity protein and DNA for SWATH-MS and OncoArray SNV analyses. We quantified 3402 proteins with 49 upregulated and 35 downregulated proteins at a minimum 2.1 fold change and FDR adjusted p-value (q-value) ≤ 0.01 when comparing tumour to normal adjacent tissue. Many of the upregulated proteins in the tumour samples are involved in extracellular matrix formation (ECM) and related intracellular pathways. In addition, proteins such as EMIL1, KBTB2, and ZCCHV involved in the regulation of ECM proteins were observed to be dysregulated in pancreatic tumours. Downregulation of pathways involved in oxygen and carbon dioxide transport were observed. Genotype data showed missense mutations in some upregulated proteins, such as MYPN, ESTY2 and SERPINB8. Approximately 11% of the dysregulated proteins, including ISLR, BP1, PTK7 and OLFL3, were predicted to be secretory proteins. These findings help in further elucidating the biology of PDAC and may aid in identifying future plausible markers for the disease.
Identifiants
pubmed: 33048956
doi: 10.1371/journal.pone.0240453
pii: PONE-D-20-17796
pmc: PMC7553299
doi:
Substances chimiques
Biomarkers, Tumor
0
Proteome
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e0240453Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
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