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Proteomics and Its Applications in Disease 2.0

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Biochemistry".

Deadline for manuscript submissions: closed (25 February 2024) | Viewed by 11263

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Prof. Dr. Lei Zhou

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1. School of Optometry, Department of Applied Biology and Chemical Technology, Research Centre for SHARP Vision (RCSV), The Hong Kong Polytechnic University, Hong Kong 999077, China
2. Singapore Eye Research Institute, The Academia, 20 College Road, Singapore 169856, Singapore
Interests: mass spectrometry; proteomics; metabolomics; disease biomarker
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Dr. Qingsong Lin

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Department of Biological Sciences, National University of Singapore, 14 Science Drive 4, Singapore 117543, Singapore
Interests: proteomics; mass spectrometry; disease biomarker; drug target identification; aquaporin biomimetic membrane
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Dr. Chuen Lam

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Guest Editor

School of Optometry, The Hong Kong Polytechnic University, Kowloon, Hong Kong, China
Interests: mass spectrometry; proteomics; post-translational modifications; disease biomarker
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

This Special Issue is a continuation of our previous successful Special Issue “Proteomics and Its Applications in Disease”.

Recent advances in mass spectrometry-based technologies, e.g., data-independent acquisition (DIA), ion mobility spectrometry (IMS), and multiple reaction monitoring (MRM), have provided superior sensitivity, reproducibility, and throughput in proteomics analysis. This allows researchers to explore diseases by assessing a deeper proteome in a relatively short time with high reproducibility and fewer missing data. No doubt, the applications of proteomics research in diseases not only provide new insights into disease mechanisms, but also novel disease biomarkers and therapeutic targets.

In this Special Issue, we invite you to contribute original research and review articles which focus on (but are not limited to) the following topics related to the applications of proteomics in diseases: disease biomarker (discovery and validation), molecular mechanisms (signaling pathway) of disease, new drug targets, the role of post-translational modifications in disease, targeted proteomics, multi-omics studies, proteomic studies on in vitro cell disease models, animal disease models, or patient cohort studies.

Prof. Dr. Lei Zhou
Dr. Qingsong Lin
Dr. Chuen Lam
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

proteomics
quantitative proteomics
biomarkers
signaling pathways
post-translational modifications
disease mechanism
novel therapeutic targets

Related Special Issues

Proteomics and Its Applications in Disease in International Journal of Molecular Sciences (16 articles)
Proteomics and Its Applications in Disease 3.0 in International Journal of Molecular Sciences (1 article)

Published Papers (10 papers)

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Research

Jump to: Review

20 pages, 5788 KiB

Open AccessArticle

Multi-Omics Characterization of Colon Mucosa and Submucosa/Wall from Crohn’s Disease Patients

by Liang Jin, Michael Macoritto, Jing Wang, Yingtao Bi, Fei Wang, Abel Suarez-Fueyo, Jesus Paez-Cortez, Chenqi Hu, Heather Knight, Ivan Mascanfroni, Matthew M. Staron, Annette Schwartz Sterman, Jean Marie Houghton, Susan Westmoreland and Yu Tian

Int. J. Mol. Sci. 2024, 25(10), 5108; https://doi.org/10.3390/ijms25105108 - 8 May 2024

Viewed by 659

Abstract

Crohn’s disease (CD) is a subtype of inflammatory bowel disease (IBD) characterized by transmural disease. The concept of transmural healing (TH) has been proposed as an indicator of deep clinical remission of CD and as a predictor of favorable treatment endpoints. Understanding the pathophysiology involved in transmural disease is critical to achieving these endpoints. However, most studies have focused on the intestinal mucosa, overlooking the contribution of the intestinal wall in Crohn’s disease. Multi-omics approaches have provided new avenues for exploring the pathogenesis of Crohn’s disease and identifying potential biomarkers. We aimed to use transcriptomic and proteomic technologies to compare immune and mesenchymal cell profiles and pathways in the mucosal and submucosa/wall compartments to better understand chronic refractory disease elements to achieve transmural healing. The results revealed similarities and differences in gene and protein expression profiles, metabolic mechanisms, and immune and non-immune pathways between these two compartments. Additionally, the identification of protein isoforms highlights the complex molecular mechanisms underlying this disease, such as decreased RTN4 isoforms (RTN4B2 and RTN4C) in the submucosa/wall, which may be related to the dysregulation of enteric neural processes. These findings have the potential to inform the development of novel therapeutic strategies to achieve TH. Full article

(This article belongs to the Special Issue Proteomics and Its Applications in Disease 2.0)

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23 pages, 2814 KiB

Open AccessArticle

Monocytic Differentiation of Human Acute Myeloid Leukemia Cells: A Proteomic and Phosphoproteomic Comparison of FAB-M4/M5 Patients with and without Nucleophosmin 1 Mutations

by Frode Selheim, Elise Aasebø, Håkon Reikvam, Øystein Bruserud and Maria Hernandez-Valladares

Int. J. Mol. Sci. 2024, 25(10), 5080; https://doi.org/10.3390/ijms25105080 - 7 May 2024

Viewed by 409

Abstract

Even though morphological signs of differentiation have a minimal impact on survival after intensive cytotoxic therapy for acute myeloid leukemia (AML), monocytic AML cell differentiation (i.e., classified as French/American/British (FAB) subtypes M4/M5) is associated with a different responsiveness both to Bcl-2 inhibition (decreased responsiveness) and possibly also bromodomain inhibition (increased responsiveness). FAB-M4/M5 patients are heterogeneous with regard to genetic abnormalities, even though monocytic differentiation is common for patients with Nucleophosmin 1 (NPM1) insertions/mutations; to further study the heterogeneity of FAB-M4/M5 patients we did a proteomic and phosphoproteomic comparison of FAB-M4/M5 patients with (n = 13) and without (n = 12) NPM1 mutations. The proteomic profile of NPM1-mutated FAB-M4/M5 patients was characterized by increased levels of proteins involved in the regulation of endocytosis/vesicle trafficking/organellar communication. In contrast, AML cells without NPM1 mutations were characterized by increased levels of several proteins involved in the regulation of cytoplasmic translation, including a large number of ribosomal proteins. The phosphoproteomic differences between the two groups were less extensive but reflected similar differences. To conclude, even though FAB classification/monocytic differentiation are associated with differences in responsiveness to new targeted therapies (e.g., Bcl-2 inhibition), our results shows that FAB-M4/M5 patients are heterogeneous with regard to important biological characteristics of the leukemic cells. Full article

(This article belongs to the Special Issue Proteomics and Its Applications in Disease 2.0)

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17 pages, 2466 KiB

Open AccessArticle

Proteomic Analysis of Prehypertensive and Hypertensive Patients: Exploring the Role of the Actin Cytoskeleton

by Sarah Al Ashmar, Gulsen Guliz Anlar, Hubert Krzyslak, Laiche Djouhri, Layla Kamareddine, Shona Pedersen and Asad Zeidan

Int. J. Mol. Sci. 2024, 25(9), 4896; https://doi.org/10.3390/ijms25094896 - 30 Apr 2024

Viewed by 539

Abstract

Hypertension is a pervasive and widespread health condition that poses a significant risk factor for cardiovascular disease, which includes conditions such as heart attack, stroke, and heart failure. Despite its widespread occurrence, the exact cause of hypertension remains unknown, and the mechanisms underlying the progression from prehypertension to hypertension require further investigation. Recent proteomic studies have shown promising results in uncovering potential biomarkers related to disease development. In this study, serum proteomic data collected from Qatar Biobank were analyzed to identify altered protein expression between individuals with normal blood pressure, prehypertension, and hypertension and to elucidate the biological pathways contributing to this disease. The results revealed a cluster of proteins, including the SRC family, CAMK2B, CAMK2D, TEC, GSK3, VAV, and RAC, which were markedly upregulated in patients with hypertension compared to those with prehypertension (fold change ≥ 1.6 or ≤−1.6, area under the curve ≥ 0.8, and q-value < 0.05). Pathway analysis showed that the majority of these proteins play a role in actin cytoskeleton remodeling. Actin cytoskeleton reorganization affects various biological processes that contribute to the maintenance of blood pressure, including vascular tone, endothelial function, cellular signaling, inflammation, fibrosis, and mechanosensing. Therefore, the findings of this study suggest a potential novel role of actin cytoskeleton-related proteins in the progression from prehypertension to hypertension. The present study sheds light on the underlying pathological mechanisms involved in hypertension and could pave the way for new diagnostic and therapeutic approaches for the treatment of this disease. Full article

(This article belongs to the Special Issue Proteomics and Its Applications in Disease 2.0)

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37 pages, 24151 KiB

Open AccessArticle

Nicotinamide Mononucleotide (NMN) Works in Type 2 Diabetes through Unexpected Effects in Adipose Tissue, Not by Mitochondrial Biogenesis

by Roua Gabriela Popescu, Anca Dinischiotu, Teodoru Soare, Ene Vlase and George Cătălin Marinescu

Int. J. Mol. Sci. 2024, 25(5), 2594; https://doi.org/10.3390/ijms25052594 - 23 Feb 2024

Viewed by 1713

Abstract

Nicotinamide mononucleotide (NMN) has emerged as a promising therapeutic intervention for age-related disorders, including type 2 diabetes. In this study, we confirmed the previously observed effects of NMN treatment on glucose uptake and investigated its underlying mechanisms in various tissues and cell lines. Through the most comprehensive proteomic analysis to date, we discovered a series of novel organ-specific effects responsible for glucose uptake as measured by the IPGTT: adipose tissue growing (suggested by increased protein synthesis and degradation and mTOR proliferation signaling upregulation). Notably, we observed the upregulation of thermogenic UCP1, promoting enhanced glucose conversion to heat in intermuscular adipose tissue while showing a surprising repressive effect on mitochondrial biogenesis in muscle and the brain. Additionally, liver and muscle cells displayed a unique response, characterized by spliceosome downregulation and concurrent upregulation of chaperones, proteasomes, and ribosomes, leading to mildly impaired and energy-inefficient protein synthesis machinery. Furthermore, our findings revealed remarkable metabolic rewiring in the brain. This involved increased production of ketone bodies, downregulation of mitochondrial OXPHOS and TCA cycle components, as well as the induction of well-known fasting-associated effects. Collectively, our data elucidate the multifaceted nature of NMN action, highlighting its organ-specific effects and their role in improving glucose uptake. These findings deepen our understanding of NMN’s therapeutic potential and pave the way for novel strategies in managing metabolic disorders. Full article

(This article belongs to the Special Issue Proteomics and Its Applications in Disease 2.0)

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12 pages, 2013 KiB

Open AccessCommunication

Variation of the 2D Pattern of Brain Proteins in Mice Infected with Taenia crassiceps ORF Strain

by Mariana Díaz-Zaragoza, Ricardo Hernández-Ávila, Abraham Landa and Pedro Ostoa-Saloma

Int. J. Mol. Sci. 2024, 25(3), 1460; https://doi.org/10.3390/ijms25031460 - 25 Jan 2024

Viewed by 562

Abstract

Some parasites are known to influence brain proteins or induce changes in the functioning of the nervous system. In this study, our objective is to demonstrate how the two-dimensional gel technique is valuable for detecting differences in protein expression and providing detailed information on changes in the brain proteome during a parasitic infection. Subsequently, we seek to understand how the parasitic infection affects the protein composition in the brain and how this may be related to changes in brain function. By analyzing de novo-expressed proteins at 2, 4, and 8 weeks post-infection compared to the brains of the control mice, we observed that proteins expressed at 2 weeks are primarily associated with neuroprotection or the initial response of the mouse brain to the infection. At 8 weeks, parasitic infection can induce oxidative stress in the brain, potentially activating signaling pathways related to the response to cellular damage. Proteins expressed at 8 weeks exhibit a pattern indicating that, as the host fails to balance the Neuro-Immuno-Endocrine network of the organism, the brain begins to undergo an apoptotic process and consequently experiences brain damage. Full article

(This article belongs to the Special Issue Proteomics and Its Applications in Disease 2.0)

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17 pages, 4066 KiB

Open AccessArticle

Targeted Proteomics Reveals Quantitative Differences in Low-Abundance Glycosyltransferases of Patients with Congenital Disorders of Glycosylation

by Roman Sakson, Lars Beedgen, Patrick Bernhard, K. Merve Alp, Nicole Lübbehusen, Ralph Röth, Beate Niesler, Marcin Luzarowski, Olga Shevchuk, Matthias P. Mayer, Christian Thiel and Thomas Ruppert

Int. J. Mol. Sci. 2024, 25(2), 1191; https://doi.org/10.3390/ijms25021191 - 18 Jan 2024

Cited by 1 | Viewed by 1070

Abstract

Protein glycosylation is an essential post-translational modification in all domains of life. Its impairment in humans can result in severe diseases named congenital disorders of glycosylation (CDGs). Most of the glycosyltransferases (GTs) responsible for proper glycosylation are polytopic membrane proteins that represent challenging targets in proteomics. We established a multiple reaction monitoring (MRM) assay to comprehensively quantify GTs involved in the processes of N-glycosylation and O- and C-mannosylation in the endoplasmic reticulum. High robustness was achieved by using an enriched membrane protein fraction of isotopically labeled HEK 293T cells as an internal protein standard. The analysis of primary skin fibroblasts from eight CDG type I patients with impaired ALG1, ALG2, and ALG11 genes, respectively, revealed a substantial reduction in the corresponding protein levels. The abundance of the other GTs, however, remained unchanged at the transcript and protein levels, indicating that there is no fail-safe mechanism for the early steps of glycosylation in the endoplasmic reticulum. The established MRM assay was shared with the scientific community via the commonly used open source Skyline software environment, including Skyline Batch for automated data analysis. We demonstrate that another research group could easily reproduce all analysis steps, even while using different LC-MS hardware. Full article

(This article belongs to the Special Issue Proteomics and Its Applications in Disease 2.0)

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22 pages, 3713 KiB

Open AccessArticle

Inhibition of HSP90 in Driver Oncogene-Defined Lung Adenocarcinoma Cell Lines: Key Proteins Underpinning Therapeutic Efficacy

by Ángela Marrugal, Irene Ferrer, Álvaro Quintanal-Villalonga, Laura Ojeda, María Dolores Pastor, Ricardo García-Luján, Amancio Carnero, Luis Paz-Ares and Sonia Molina-Pinelo

Int. J. Mol. Sci. 2023, 24(18), 13830; https://doi.org/10.3390/ijms241813830 - 7 Sep 2023

Cited by 1 | Viewed by 1246

Abstract

The use of 90 kDa heat shock protein (HSP90) inhibition as a therapy in lung adenocarcinoma remains limited due to moderate drug efficacy, the emergence of drug resistance, and early tumor recurrence. The main objective of this research is to maximize treatment efficacy in lung adenocarcinoma by identifying key proteins underlying HSP90 inhibition according to molecular background, and to search for potential biomarkers of response to this therapeutic strategy. Inhibition of the HSP90 chaperone was evaluated in different lung adenocarcinoma cell lines representing the most relevant molecular alterations (EGFR mutations, KRAS mutations, or EML4-ALK translocation) and wild-type genes found in each tumor subtype. The proteomic technique iTRAQ was used to identify proteomic profiles and determine which biological pathways are involved in the response to HSP90 inhibition in lung adenocarcinoma. We corroborated the greater efficacy of HSP90 inhibition in EGFR mutated or EML4-ALK translocated cell lines. We identified proteins specifically and significantly deregulated after HSP90 inhibition for each molecular alteration. Two proteins, ADI1 and RRP1, showed independently deregulated molecular patterns. Functional annotation of the altered proteins suggested that apoptosis was the only pathway affected by HSP90 inhibition across all molecular subgroups. The expression of ADI1 and RRP1 could be used to monitor the correct inhibition of HSP90 in lung adenocarcinoma. In addition, proteins such as ASS1, ITCH, or UBE2L3 involved in pathways related to the inhibition of a particular molecular background could be used as potential response biomarkers, thereby improving the efficacy of this therapeutic approach to combat lung adenocarcinoma. Full article

(This article belongs to the Special Issue Proteomics and Its Applications in Disease 2.0)

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24 pages, 5257 KiB

Open AccessArticle

Differential Responses of Retinal Neurons and Glia Revealed via Proteomic Analysis on Primary and Secondary Retinal Ganglion Cell Degeneration

by Jacky M. K. Kwong, Joseph Caprioli, Joanne C. Y. Lee, Yifan Song, Feng-Juan Yu, Jingfang Bian, Ying-Hon Sze, King-Kit Li, Chi-Wai Do, Chi-Ho To and Thomas Chuen Lam

Int. J. Mol. Sci. 2023, 24(15), 12109; https://doi.org/10.3390/ijms241512109 - 28 Jul 2023

Viewed by 1109

Abstract

To explore the temporal profile of retinal proteomes specific to primary and secondary retinal ganglion cell (RGC) loss. Unilateral partial optic nerve transection (pONT) was performed on the temporal side of the rat optic nerve. Temporal and nasal retinal samples were collected at 1, 4 and 8 weeks after pONT (n = 4 each) for non-biased profiling with a high-resolution hybrid quadrupole time-of-flight mass spectrometry running on label-free SWATH^TM acquisition (SCIEX). An information-dependent acquisition ion library was generated using ProteinPilot 5.0 and OneOmics cloud bioinformatics. Combined proteome analysis detected 2531 proteins with a false discovery rate of <1%. Compared to the nasal retina, 10, 25 and 61 significantly regulated proteins were found in the temporal retina at 1, 4, and 8 weeks, respectively (p < 0.05, FC ≥ 1.4 or ≤0.7). Eight proteins (ALDH1A1, TRY10, GFAP, HBB-B1, ALB, CDC42, SNCG, NEFL) were differentially expressed for at least two time points. The expressions of ALDH1A1 and SNCG at nerve fibers were decreased along with axonal loss. Increased ALDH1A1 localization in the inner nuclear layer suggested stress response. Increased GFAP expression demonstrated regional reactivity of astrocytes and Muller cells. Meta-analysis of gene ontology showed a pronounced difference in endopeptidase and peptidase inhibitor activity. Temporal proteomic profiling demonstrates established and novel protein targets associated with RGC damage. Full article

(This article belongs to the Special Issue Proteomics and Its Applications in Disease 2.0)

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Review

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37 pages, 1001 KiB

Open AccessReview

Circulating Proteins as Diagnostic Markers in Gastric Cancer

by Ombretta Repetto, Roberto Vettori, Agostino Steffan, Renato Cannizzaro and Valli De Re

Int. J. Mol. Sci. 2023, 24(23), 16931; https://doi.org/10.3390/ijms242316931 - 29 Nov 2023

Cited by 6 | Viewed by 1564

Abstract

Gastric cancer (GC) is a highly malignant disease affecting humans worldwide and has a poor prognosis. Most GC cases are detected at advanced stages due to the cancer lacking early detectable symptoms. Therefore, there is great interest in improving early diagnosis by implementing targeted prevention strategies. Markers are necessary for early detection and to guide clinicians to the best personalized treatment. The current semi-invasive endoscopic methods to detect GC are invasive, costly, and time-consuming. Recent advances in proteomics technologies have enabled the screening of many samples and the detection of novel biomarkers and disease-related signature signaling networks. These biomarkers include circulating proteins from different fluids (e.g., plasma, serum, urine, and saliva) and extracellular vesicles. We review relevant published studies on circulating protein biomarkers in GC and detail their application as potential biomarkers for GC diagnosis. Identifying highly sensitive and highly specific diagnostic markers for GC may improve patient survival rates and contribute to advancing precision/personalized medicine. Full article

(This article belongs to the Special Issue Proteomics and Its Applications in Disease 2.0)

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34 pages, 2500 KiB

Open AccessReview

Searching for Atherosclerosis Biomarkers by Proteomics: A Focus on Lesion Pathogenesis and Vulnerability

by Gabriele Nieddu, Marilena Formato and Antonio Junior Lepedda

Int. J. Mol. Sci. 2023, 24(20), 15175; https://doi.org/10.3390/ijms242015175 - 14 Oct 2023

Cited by 2 | Viewed by 1215

Abstract

Plaque rupture and thrombosis are the most important clinical complications in the pathogenesis of stroke, coronary arteries, and peripheral vascular diseases. The identification of early biomarkers of plaque presence and susceptibility to ulceration could be of primary importance in preventing such life-threatening events. With the improvement of proteomic tools, large-scale technologies have been proven valuable in attempting to unravel pathways of atherosclerotic degeneration and identifying new circulating markers to be utilized either as early diagnostic traits or as targets for new drug therapies. To address these issues, different matrices of human origin, such as vascular cells, arterial tissues, plasma, and urine, have been investigated. Besides, proteomics was also applied to experimental atherosclerosis in order to unveil significant insights into the mechanisms influencing atherogenesis. This narrative review provides an overview of the last twenty years of omics applications to the study of atherogenesis and lesion vulnerability, with particular emphasis on lipoproteomics and vascular tissue proteomics. Major issues of tissue analyses, such as plaque complexity, sampling, availability, choice of proper controls, and lipoproteins purification, will be raised, and future directions will be addressed. Full article

(This article belongs to the Special Issue Proteomics and Its Applications in Disease 2.0)

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