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Open AccessArticle

Serum-Based Proteomics Profiling in Adult Patients with Cystic Fibrosis

1
Proteomics Resource Unit, Obesity Research Center, College of Medicine, King Saud University, P.O. Box 2925 (98), Riyadh 11461, Saudi Arabia
2
Department of Biochemistry and Molecular Medicine, College of Medicine, Al Faisal University, Riyadh 11533, Saudi Arabia
3
Department of Community Health Sciences, College of Applied Medical Sciences, King Saud University, 183T11, Riyadh 11495, Saudi Arabia
4
Department of Genetics, King Faisal Specialist Hospital and Research Centre (KFSHRC), Zahrawi Street, Al Maather, Riyadh 11211, Saudi Arabia
5
The National Center for Biotechnology (NCB), Life Science and Environment Research Institute, King Abdulaziz City for Science and Technology (KACST), P.O. Box 6086, Riyadh 12354, Saudi Arabia
6
Department of Medicine, College of Medicine, King Saud University, P.O. Box 2925 (98), Riyadh 11461, Saudi Arabia
7
Lung Transplant Section, Organ Transplant Center, King Faisal Specialist Hospital and Research Center, Zahrawi Street, Al Maather, Riyadh 11211, Saudi Arabia
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Department of Chemistry, Memorial University of Newfoundland, St. John’s, NL A1B 3X7, Canada
*
Authors to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(19), 7415; https://doi.org/10.3390/ijms21197415
Received: 7 July 2020 / Revised: 16 September 2020 / Accepted: 28 September 2020 / Published: 8 October 2020
(This article belongs to the Special Issue Biomarkers in Rare Diseases)
Cystic fibrosis (CF), the most common lethal autosomal recessive disorder among Caucasians, is caused by mutations in the CF transmembrane conductance regulator (CFTR) chloride channel gene. Despite significant advances in the management of CF patients, novel disease-related biomarkers and therapies must be identified. We performed serum proteomics profiling in CF patients (n = 28) and healthy subjects (n = 10) using the 2D-DIGE MALDI-TOF proteomic approach. Out of a total of 198 proteins identified, 134 showed a statistically significant difference in abundance and a 1.5-fold change (ANOVA, p < 0.05), including 80 proteins with increased abundance and 54 proteins with decreased abundance in CF patients. A multiple reaction monitoring-mass spectrometry analysis of six differentially expressed proteins identified by a proteomic approach (DIGE-MALD-MS) showed a significant increase in C3 and CP proteins and a decrease in APOA1, Complement C1, Hp, and RBP4proteins compared with healthy controls. Fifteen proteins were identified as potential biomarkers for CF diagnosis. An ingenuity pathway analysis of the differentially regulated proteins indicates that the central nodes dysregulated in CF subjects involve pro-inflammatory cytokines, ERK1/2, and P38 MAPK, which are primarily involved in catalytic activities and metabolic processes. The involved canonical pathways include those related to FXR/RXR, LXR/RXR, acute phase response, IL12, nitric oxide, and reactive oxygen species in macrophages. Our data support the current efforts toward augmenting protease inhibitors in patients with CF. Perturbations in lipid and vitamin metabolism frequently observed in CF patients may be partly due to abnormalities in their transport mechanism. View Full-Text
Keywords: cystic fibrosis; CFTR; proteomics; DIGE-MALDI/TOF; biomarker cystic fibrosis; CFTR; proteomics; DIGE-MALDI/TOF; biomarker
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MDPI and ACS Style

Benabdelkamel, H.; Alamri, H.; Okla, M.; Masood, A.; Abdel Jabar, M.; Alanazi, I.O.; Alfadda, A.A.; Nizami, I.; Dasouki, M.; Abdel Rahman, A.M. Serum-Based Proteomics Profiling in Adult Patients with Cystic Fibrosis. Int. J. Mol. Sci. 2020, 21, 7415. https://doi.org/10.3390/ijms21197415

AMA Style

Benabdelkamel H, Alamri H, Okla M, Masood A, Abdel Jabar M, Alanazi IO, Alfadda AA, Nizami I, Dasouki M, Abdel Rahman AM. Serum-Based Proteomics Profiling in Adult Patients with Cystic Fibrosis. International Journal of Molecular Sciences. 2020; 21(19):7415. https://doi.org/10.3390/ijms21197415

Chicago/Turabian Style

Benabdelkamel, Hicham; Alamri, Hanadi; Okla, Meshail; Masood, Afshan; Abdel Jabar, Mai; Alanazi, Ibrahim O.; Alfadda, Assim A.; Nizami, Imran; Dasouki, Majed; Abdel Rahman, Anas M. 2020. "Serum-Based Proteomics Profiling in Adult Patients with Cystic Fibrosis" Int. J. Mol. Sci. 21, no. 19: 7415. https://doi.org/10.3390/ijms21197415

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