SWATH-MS based proteomic profiling of pancreatic ductal adenocarcinoma tumours reveals the interplay between the extracellular matrix and related intracellular pathways

Ekene Emmanuel Nweke; Previn Naicker; Shaun Aron; Stoyan Stoychev; John Devar; David L Tabb; Jones Omoshoro-Jones; Martin Smith; Geoffrey Candy

doi:10.1371/journal.pone.0240453

SWATH-MS based proteomic profiling of pancreatic ductal adenocarcinoma tumours reveals the interplay between the extracellular matrix and related intracellular pathways

PLoS One. 2020 Oct 13;15(10):e0240453. doi: 10.1371/journal.pone.0240453. eCollection 2020.

Authors

Ekene Emmanuel Nweke¹, Previn Naicker², Shaun Aron³, Stoyan Stoychev², John Devar¹, David L Tabb⁴, Jones Omoshoro-Jones¹, Martin Smith¹, Geoffrey Candy¹

Affiliations

¹ Department of Surgery, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
² Department of Biosciences, Council for Scientific and Industrial Research, Pretoria, South Africa.
³ Sydney Brenner Institute for Molecular Bioscience, University of the Witwatersrand, Johannesburg, South Africa.
⁴ Bioinformatics Unit, South African Tuberculosis Bioinformatics Initiative, Division of Molecular Biology and Human Genetics, Department of Biomedical Sciences, Stellenbosch University, Cape Town, South Africa.

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aged
Aged, 80 and over
Biomarkers, Tumor / genetics*
Biomarkers, Tumor / metabolism*
Carcinoma, Pancreatic Ductal / genetics
Carcinoma, Pancreatic Ductal / metabolism
Carcinoma, Pancreatic Ductal / pathology*
Carcinoma, Pancreatic Ductal / surgery
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
Pancreatic Neoplasms / metabolism
Pancreatic Neoplasms / pathology*
Pancreatic Neoplasms / surgery
Polymorphism, Single Nucleotide*
Prognosis
Proteome / analysis*

Substances

Biomarkers, Tumor
Proteome

Grants and funding

The study was funded by the Council for Scientific and Industrial Research and the South African Medical Research Council through a grant awarded to the Wits Common Epithelial Cancer Research Centre. DLT was supported in part by a Strategic Health Innovation Partnership (SHIP) grant from the South African (SA) Department of Science and Technology (DST) and the SA Medical Research Council (SAMRC) to Gerhard Walzl. GC is funded by The Cancer Association of South Africa (CANSA). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.