Special Issue "Proteomic Biomarkers in Human Diseases"

A special issue of Proteomes (ISSN 2227-7382).

Deadline for manuscript submissions: closed (10 March 2018)

Special Issue Editors

Guest Editor
Prof. Dr. Stephen Pennington

Department of Pathology, University College Dublin, Dublin, Ireland
Website | E-Mail
Interests: protein biomarkers, oncology, inflammatory arthritis, MRM, mass spectrometry, clinical diagnostics
Guest Editor
Prof. Dr. Jennifer Van Eyk

Advanced Clinical Biosystems Research Institute, Cedars-Sinai Medical Center, Los Angeles, USA
Website | E-Mail
Interests: protein biomarkers, inflammatory arthritis, MRM, mass spectrometry, clinical diagnostics; cardiovascular, sample preparation, automation

Special Issue Information

Dear Colleagues,

The latest methods for protein identification and quantification offer the opportunity to systematically study disease mechanisms as well as identify biomarkers and measure markers for the diagnosis and prognosis of disease and those that might predict or monitor a patient's response to treatment. Notably, advances in mass spectrometry instrumentation and other proteomic methods are leading to advances in the field of clinical proteomics towards the multiplexed analysis of large numbers of patient samples. A key challenge in this field today is translating this wealth of knowledge into clinically useful outputs that can benefit patients and improve the efficiency of hospital laboratories.

We invite you to contribute original studies and reviews to this Special Issue that will include applications of various biomarker panels for cancer, cardiovascular, and neurological diseases, as well as the role of proteomics in other pathological processes. We are interested in receiving manuscripts describing all aspects of the current challenges in applying proteomic technologies to the development of disease biomarkers for clinical utility. These challenges include the need for analytical rigor, reproducibility between laboratories, standardization of sample collection, storage and processing, proteomics workflows, data analysis and reporting. We are particularly interested in receiving original studies covering the discovery, measurement and clinical application of protein biomarkers and their integration with other molecular and clinical data.

We look forward to receiving your manuscripts and compiling an informative collection of pertinent articles that will serve to advance the arena of disease markers.

Sincerely,

Prof. Dr. Stephen Pennington
Prof. Dr. Jennifer Van Eyk
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 papers will be 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. Proteomes is an international peer-reviewed open access quarterly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 550 CHF (Swiss Francs). 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

  • Clinical Proteomics
  • Biomarker Discovery
  • Oncology
  • Neuroscience/Psychiatry
  • Clinical Pathology
  • Technical and Analytical Control Methods
  • Proteomics
  • Mass Spectrometry

Published Papers (9 papers)

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Research

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Open AccessArticle Proteomics Analysis to Assess the Role of Mitochondria in BRCA1-Mediated Breast Tumorigenesis
Received: 16 March 2018 / Revised: 22 March 2018 / Accepted: 23 March 2018 / Published: 27 March 2018
Cited by 3 | PDF Full-text (15617 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Mitochondria are the organelles deputed to energy production, but they are also involved in carcinogenesis, cancer progression, and metastasis, playing a role in altered energy metabolism in cancer cells. Mitochondrial metabolism is connected with several mitochondrial pathways such as ROS signaling, Ca2+ [...] Read more.
Mitochondria are the organelles deputed to energy production, but they are also involved in carcinogenesis, cancer progression, and metastasis, playing a role in altered energy metabolism in cancer cells. Mitochondrial metabolism is connected with several mitochondrial pathways such as ROS signaling, Ca2+ homeostasis, mitophagy, and mitochondrial biogenesis. These pathways are merged in an interactive super-network that seems to play a crucial role in cancer. Germline mutations of the BRCA1 gene account for 5–10% of breast cancers and confer a risk of developing the disease 10- to 20-fold much higher than in non-carriers. By considering metabolic networks that could reconcile both genetic and non-genetic causal mechanisms in BRCA1 driven tumorigenesis, we herein based our study on the hypothesis that BRCA1 haploinsufficiency might drive metabolic rewiring in breast epithelial cells, acting as a push toward malignant transformation. Using 2D-DIGE we analyzed and compared the mitochondrial proteomic profile of sporadic breast cancer cell line (MCF7) and BRCA1 mutated breast cancer cell line (HCC1937). Image analysis was carried out with Decider Software, and proteins differentially expressed were identified by LC-MS/MS on a quadrupole-orbitrap mass spectrometer Q-Exactive. Ingenuity pathways analysis software was used to analyze the fifty-three mitochondrial proteins whose expression resulted significantly altered in response to BRCA1 mutation status. Mitochondrial Dysfunction and oxidative phosphorylation, and energy production and nucleic acid metabolism were, respectively, the canonical pathway and the molecular function mainly affected. Western blotting analysis was done to validate the expression and the peculiar mitochondrial compartmentalization of specific proteins such us HSP60 and HIF-1α. Particularly intriguing is the correlation between BRCA1 mutation status and HIF-1α localization into the mitochondria in a BRCA1 dependent manner. Data obtained led us to hypothesize an interesting connection between BRCA1 and mitochondria pathways, capable to trigger metabolic changes, which, in turn, sustain the high energetic and anabolic requirements of the malignant phenotype. Full article
(This article belongs to the Special Issue Proteomic Biomarkers in Human Diseases)
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Open AccessFeature PaperArticle Proteome Profiling of Diabetic Mellitus Patient Urine for Discovery of Biomarkers by Comprehensive MS-Based Proteomics
Received: 27 December 2017 / Revised: 19 January 2018 / Accepted: 2 February 2018 / Published: 6 February 2018
PDF Full-text (2235 KB) | HTML Full-text | XML Full-text
Abstract
Diabetic mellitus (DM) is a disease that affects glucose homeostasis and causes complications, such as diabetic nephropathy (DN). For early diagnosis of DN, microalbuminuria is currently one of the most frequently used biomarkers. However, more early diagnostic biomarkers are desired in addition to [...] Read more.
Diabetic mellitus (DM) is a disease that affects glucose homeostasis and causes complications, such as diabetic nephropathy (DN). For early diagnosis of DN, microalbuminuria is currently one of the most frequently used biomarkers. However, more early diagnostic biomarkers are desired in addition to microalbuminuria. In this study, we performed comprehensive proteomics analysis of urine proteomes of diabetic mellitus patients without microalbuminuria and healthy volunteers to compare the protein profiles by mass spectrometry. With high confidence criteria, 942 proteins in healthy volunteer urine and 645 proteins in the DM patient urine were identified with label-free semi-quantitation, respectively. Gene ontology and pathway analysis were performed with the proteins, which were up- or down-regulated in the DM patient urine to elucidate significant changes in pathways. The discovery of a useful biomarker for early DN discovery is expected. Full article
(This article belongs to the Special Issue Proteomic Biomarkers in Human Diseases)
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Open AccessArticle Quantification of Cardiovascular Disease Biomarkers in Human Platelets by Targeted Mass Spectrometry
Received: 3 October 2017 / Revised: 7 November 2017 / Accepted: 13 November 2017 / Published: 15 November 2017
Cited by 3 | PDF Full-text (1266 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Platelets are known to be key players in thrombosis and hemostasis, contributing to the genesis and progression of cardiovascular diseases. Due to their pivotal role in human physiology and pathology, platelet function is regulated tightly by numerous factors which have either stimulatory or [...] Read more.
Platelets are known to be key players in thrombosis and hemostasis, contributing to the genesis and progression of cardiovascular diseases. Due to their pivotal role in human physiology and pathology, platelet function is regulated tightly by numerous factors which have either stimulatory or inhibitory effects. A variety of factors, e.g., collagen, fibrinogen, ADP, vWF, thrombin, and thromboxane promote platelet adhesion and aggregation by utilizing multiple intracellular signal cascades. To quantify platelet proteins for this work, a targeted proteomics workflow was applied. In detail, platelets are isolated and lyzed, followed by a tryptic protein digest. Subsequently, a mix of stable isotope-labeled peptides of interesting biomarker proteins in concentrations ranging from 0.1 to 100 fmol is added to 3 μg digest. These peptides are used as an internal calibration curve to accurately quantify endogenous peptides and corresponding proteins in a pooled platelet reference sample by nanoLC-MS/MS with parallel reaction monitoring. In order to assure a valid quantification, limit of detection (LOD) and limit of quantification (LOQ), as well as linear range, were determined. This quantification of platelet activation and proteins by targeted mass spectrometry may enable novel diagnostic strategies in the detection and prevention of cardiovascular diseases. Full article
(This article belongs to the Special Issue Proteomic Biomarkers in Human Diseases)
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Open AccessArticle Performance of a Multiplex Serological Helicobacter pylori Assay on a Novel Microfluidic Assay Platform
Received: 29 August 2017 / Revised: 19 September 2017 / Accepted: 29 September 2017 / Published: 3 October 2017
Cited by 2 | PDF Full-text (1461 KB) | HTML Full-text | XML Full-text
Abstract
Infection with Helicobacter pylori (H. pylori) occurs in 50% of the world population, and is associated with the development of ulcer and gastric cancer. Serological diagnostic tests indicate an H. pylori infection by detecting antibodies directed against H. pylori proteins. In [...] Read more.
Infection with Helicobacter pylori (H. pylori) occurs in 50% of the world population, and is associated with the development of ulcer and gastric cancer. Serological diagnostic tests indicate an H. pylori infection by detecting antibodies directed against H. pylori proteins. In addition to line blots, multiplex assay platforms provide smart solutions for the simultaneous analysis of antibody responses towards several H. pylori proteins. We used seven H. pylori proteins (FliD, gGT, GroEL, HpaA, CagA, VacA, and HP0231) and an H. pylori lysate for the development of a multiplex serological assay on a novel microfluidic platform. The reaction limited binding regime in the microfluidic channels allows for a short incubation time of 35 min. The developed assay showed very high sensitivity (99%) and specificity (100%). Besides sensitivity and specificity, the technical validation (intra-assay CV = 3.7 ± 1.2% and inter-assay CV = 5.5 ± 1.2%) demonstrates that our assay is also a robust tool for the analysis of the H. pylori-specific antibody response. The integration of the virulence factors CagA and VacA allow for the assessment of the risk for gastric cancer development. The short assay time and the performance of the platform shows the potential for implementation of such assays in a clinical setting. Full article
(This article belongs to the Special Issue Proteomic Biomarkers in Human Diseases)
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Review

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Open AccessReview Integrated Chemometrics and Statistics to Drive Successful Proteomics Biomarker Discovery
Received: 30 March 2018 / Revised: 19 April 2018 / Accepted: 25 April 2018 / Published: 26 April 2018
Cited by 3 | PDF Full-text (1184 KB) | HTML Full-text | XML Full-text
Abstract
Protein biomarkers are of great benefit for clinical research and applications, as they are powerful means for diagnosing, monitoring and treatment prediction of different diseases. Even though numerous biomarkers have been reported, the translation to clinical practice is still limited. This mainly due [...] Read more.
Protein biomarkers are of great benefit for clinical research and applications, as they are powerful means for diagnosing, monitoring and treatment prediction of different diseases. Even though numerous biomarkers have been reported, the translation to clinical practice is still limited. This mainly due to: (i) incorrect biomarker selection, (ii) insufficient validation of potential biomarkers, and (iii) insufficient clinical use. In this review, we focus on the biomarker selection process and critically discuss the chemometrical and statistical decisions made in proteomics biomarker discovery to increase to selection of high value biomarkers. The characteristics of the data, the computational resources, the type of biomarker that is searched for and the validation strategy influence the decision making of the chemometrical and statistical methods and a decision made for one component directly influences the choice for another. Incorrect decisions could increase the false positive and negative rate of biomarkers which requires independent confirmation of outcome by other techniques and for comparison between different related studies. There are few guidelines for authors regarding data analysis documentation in peer reviewed journals, making it hard to reproduce successful data analysis strategies. Here we review multiple chemometrical and statistical methods for their value in proteomics-based biomarker discovery and propose to include key components in scientific documentation. Full article
(This article belongs to the Special Issue Proteomic Biomarkers in Human Diseases)
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Open AccessReview Molecular Pathophysiology of Epithelial Barrier Dysfunction in Inflammatory Bowel Diseases
Received: 11 January 2018 / Revised: 24 March 2018 / Accepted: 26 March 2018 / Published: 31 March 2018
Cited by 3 | PDF Full-text (2840 KB) | HTML Full-text | XML Full-text
Abstract
Over the years, the scientific community has explored myriads of theories in search of the etiology and a cure for inflammatory bowel disease (IBD). The cumulative evidence has pointed to the key role of the intestinal barrier and the breakdown of these mechanisms [...] Read more.
Over the years, the scientific community has explored myriads of theories in search of the etiology and a cure for inflammatory bowel disease (IBD). The cumulative evidence has pointed to the key role of the intestinal barrier and the breakdown of these mechanisms in IBD. More and more scientists and clinicians are embracing the concept of the impaired intestinal epithelial barrier and its role in the pathogenesis and natural history of IBD. However, we are missing a key tool that bridges these scientific insights to clinical practice. Our goal is to overcome the limitations in understanding the molecular physiology of intestinal barrier function and develop a clinical tool to assess and quantify it. This review article explores the proteins in the intestinal tissue that are pivotal in regulating intestinal permeability. Understanding the molecular pathophysiology of impaired intestinal barrier function in IBD may lead to the development of a biochemical method of assessing intestinal tissue integrity which will have a significant impact on the development of novel therapies targeting the intestinal mucosa. Full article
(This article belongs to the Special Issue Proteomic Biomarkers in Human Diseases)
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Open AccessFeature PaperReview Exploring the Psoriatic Arthritis Proteome in Search of Novel Biomarkers
Received: 18 December 2017 / Revised: 16 January 2018 / Accepted: 21 January 2018 / Published: 24 January 2018
Cited by 2 | PDF Full-text (421 KB) | HTML Full-text | XML Full-text
Abstract
Psoriatic arthritis (PsA) is an inflammatory arthritis which develops in up to one-third of patients suffering from the cutaneous disorder, psoriasis. The complex and heterogeneous nature of PsA renders it difficult to diagnose, leading to poor outcomes and, therefore, warrants an examination into [...] Read more.
Psoriatic arthritis (PsA) is an inflammatory arthritis which develops in up to one-third of patients suffering from the cutaneous disorder, psoriasis. The complex and heterogeneous nature of PsA renders it difficult to diagnose, leading to poor outcomes and, therefore, warrants an examination into soluble biomarkers, which may facilitate early detection of the disease. Protein biomarkers are a dynamic resource of pathophysiological information able to provide an immediate reflection of pathological changes caused by disease. Investigations of the serum and synovial fluid of PsA patients has provided new insights into the molecular basis of this disease and led to the identification of sensitive diagnostic and prognostic biomarkers. The collection of novel PsA biomarkers identified through proteomic studies has been reviewed below. Full article
(This article belongs to the Special Issue Proteomic Biomarkers in Human Diseases)
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Open AccessReview Mass Spectrometric Studies of Apolipoprotein Proteoforms and Their Role in Lipid Metabolism and Type 2 Diabetes
Received: 15 September 2017 / Revised: 10 October 2017 / Accepted: 11 October 2017 / Published: 15 October 2017
Cited by 3 | PDF Full-text (188 KB) | HTML Full-text | XML Full-text
Abstract
Apolipoproteins function as structural components of lipoprotein particles, cofactors for enzymes, and ligands for cell-surface receptors. Most of the apoliporoteins exhibit proteoforms, arising from single nucleotide polymorphisms (SNPs) and post-translational modifications such as glycosylation, oxidation, and sequence truncations. Reviewed here are recent studies [...] Read more.
Apolipoproteins function as structural components of lipoprotein particles, cofactors for enzymes, and ligands for cell-surface receptors. Most of the apoliporoteins exhibit proteoforms, arising from single nucleotide polymorphisms (SNPs) and post-translational modifications such as glycosylation, oxidation, and sequence truncations. Reviewed here are recent studies correlating apolipoproteins proteoforms with the specific clinical measures of lipid metabolism and cardiometabolic risk. Targeted mass spectrometric immunoassays toward apolipoproteins A-I, A-II, and C-III were applied on large cross-sectional and longitudinal clinical cohorts. Several correlations were observed, including greater apolipoprotein A-I and A-II oxidation in patients with diabetes and cardiovascular disease, and a divergent apoC-III proteoforms association with plasma triglycerides, indicating significant differences in the metabolism of the individual apoC-III proteoforms. These are the first studies of their kind, correlating specific proteoforms with clinical measures in order to determine their utility as potential clinical biomarkers for disease diagnosis, risk stratification, and therapy decisions. Such studies provide the impetus for the further development and clinical translation of MS-based protein tests. Full article
(This article belongs to the Special Issue Proteomic Biomarkers in Human Diseases)
Open AccessReview Role of Salivary Biomarkers in Detection of Cardiovascular Diseases (CVD)
Received: 4 June 2017 / Revised: 3 August 2017 / Accepted: 5 August 2017 / Published: 7 August 2017
Cited by 3 | PDF Full-text (993 KB) | HTML Full-text | XML Full-text
Abstract
Human whole mouth saliva (WMS) is secreted by salivary glands, namely parotid, submandibular/sublingual and other minor glands of the oral cavity. It is secreted in a systematic way, and contain informative proteins and peptides for the early detection of contagious diseases and organ-related [...] Read more.
Human whole mouth saliva (WMS) is secreted by salivary glands, namely parotid, submandibular/sublingual and other minor glands of the oral cavity. It is secreted in a systematic way, and contain informative proteins and peptides for the early detection of contagious diseases and organ-related diseases. The role of WMS as a liquid biopsy for the detection of cardiovascular diseases (CVD) through Myoglobin (MYO), Cardiac troponin I (cTnI), Creatine phosphokinase MB (CK-MB), Myeloperoxidase (MPO), brain natriuretic peptide (NT-proBNP), Exosomal miRNA, C-Reactive Protein (CRP), Matrix metalloproteinase-8 (MMP-8), MMP-9 and tissue inhibitor of MMP-8 (TIMP-1), leukotriene B4 has been well reported in last decade, that have been reviewed in the literature comprehensively below. Full article
(This article belongs to the Special Issue Proteomic Biomarkers in Human Diseases)
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