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Recent Advances of Proteomics Applied to Cancer and Human Diseases

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (31 January 2021) | Viewed by 46029

Special Issue Editors

Prof. Dr. Michel Sève

E-Mail Website
Guest Editor
CNRS, UMR 5525, VetAgro Sup, Grenoble INP, TIMC, Université Grenoble Alpes, 38000 Grenoble, France
Interests: proteomics; metabolomics; environmental exposure
Special Issues, Collections and Topics in MDPI journals
Dr. Walid Rachidi

E-Mail Website
Guest Editor
CEA, INSERM, IRIG-BGE UA13, Université Grenoble Alpes, 38000 Grenoble, France
Interests: skin cancer; aging; stem cells; skin organoids; UV; DNA repair; genetotoxicity
Special Issues, Collections and Topics in MDPI journals
Dr. Sandrine Bourgoin-Voillard

E-Mail Website
Guest Editor
CNRS, UMR 5525, VetAgro Sup, Grenoble INP, TIMC, Université Grenoble Alpes, 38000 Grenoble, France
Interests: proteomics; mass spectrometry-based proteomics; environmental exposure, biomarkers
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The definition of proteomics, the technics used for proteome research, has changed in the past from the obtention of a simple list of the “proteins expressed by a genome, or by a cell or a tissue type”; to a more complex “comprehensive, quantitative description of protein expression and its changes under the influence of biological perturbations such as disease or drug treatment”; and finally, more recently, to a very complex “identification and quantification of proteins, but also the determination of their localization, modifications, interactions, activities, and, ultimately, their function”. Nowadays, we talk about  proteoforms rather than proteins. The fast developement of these techniques, tools, types of equipment, and bioinformatics in this field presents many opportunities to answer complex biological questions, particularly in the field of cancer.Cancer is a complex disease with dysregulation of normal cellular signaling networks that control cell behaviors, such as proliferation and apoptosis, caused by genetic, genomic, and epigenetic alterations at the cellular or tissue levels. It includes several modifications at the proteome level, such as modifications of protein expression level or localizations; abnormal protein expressions; modifications of post-translational patterns; and altered signalization, metabolic pathways, and immune system.In this Special Issue, we would like to gather contributions reporting very recent advances in the developement of proteomics in cancer. We invite you to participate in this Special Issue, and we expect original works addressing the biological models (2D and 3D cellular models, biological fluids, and tissues from biobanks) suited for proteomics analysis, the discovery of new protein biomarkers and targets, the determination of post-translational modifications, their profiles, cross-talks and implications in signal transduction, cellular reprogrammation, and immune response during tumoral progression.

Prof. Dr. Michel Sève
Dr. Walid Rachidi
Dr. Sandrine Bourgoin-Voillard
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

  • Cancer
  • Proteomics
  • Post-translational modifications
  • Signaling
  • Cellular reprogramming
  • Immune response
  • Network
  • Modelling
  • Biomarker
  • Drug target

Published Papers (16 papers)

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Research

Jump to: Review

14 pages, 3092 KiB  
Article
Serum Proteome Signatures of Anti-SARS-CoV-2 Vaccinated Healthcare Workers in Greece Associated with Their Prior Infection Status
by Eleni Stamoula, Eleana Sarantidi, Vasilis Dimakopoulos, Alexandra Ainatzoglou, Ioannis Dardalas, Georgios Papazisis, Konstantina Kontopoulou and Athanasios K. Anagnostopoulos
Int. J. Mol. Sci. 2022, 23(17), 10153; https://doi.org/10.3390/ijms231710153 - 05 Sep 2022
Cited by 2 | Viewed by 1723
Abstract
Over the course of the pandemic, proteomics, being in the frontline of anti-COVID-19 research, has massively contributed to the investigation of molecular pathogenic properties of the virus. However, data on the proteome on anti-SARS-CoV-2 vaccinated individuals remain scarce. This study aimed to identify [...] Read more.
Over the course of the pandemic, proteomics, being in the frontline of anti-COVID-19 research, has massively contributed to the investigation of molecular pathogenic properties of the virus. However, data on the proteome on anti-SARS-CoV-2 vaccinated individuals remain scarce. This study aimed to identify the serum proteome characteristics of anti-SARS-CoV-2 vaccinated individuals who had previously contracted the virus and comparatively assess them against those of virus-naïve vaccine recipients. Blood samples of n = 252 individuals, out of whom n = 35 had been previously infected, were collected in the “G. Gennimatas” General Hospital of Thessaloniki, from 4 January 2021 to 31 August 2021. All participants received the BNT162b2 mRNA COVID-19 vaccine (Pfizer/BioNTech). A label-free quantitative proteomics LC-MS/MS approach was undertaken, and the identified proteins were analyzed using the GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes) databases as well as processed by bioinformatics tools. Titers of total RBD-specific IgGs against SARS-CoV-2 were also determined using the SARS-CoV-2 IgG II Quant assay. A total of 47 proteins were significantly differentially expressed, the majority of which were down-regulated in sera of previously infected patients compared to virus-naïve controls. Several pathways were affected supporting the crucial role of the humoral immune response in the protection against SARS-CoV-2 infection provided by COVID-19 vaccination. Overall, our comprehensive proteome profiling analysis contributes novel knowledge of the mechanisms of immune response induced by anti-SARS-CoV-2 vaccination and identified protein signatures reflecting the immune status of vaccine recipients. Full article
(This article belongs to the Special Issue Recent Advances of Proteomics Applied to Cancer and Human Diseases)
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28 pages, 4342 KiB  
Article
Quantitative Proteomic Approach Reveals Altered Metabolic Pathways in Response to the Inhibition of Lysine Deacetylases in A549 Cells under Normoxia and Hypoxia
by Alfonso Martín-Bernabé, Josep Tarragó-Celada, Valérie Cunin, Sylvie Michelland, Roldán Cortés, Johann Poignant, Cyril Boyault, Walid Rachidi, Sandrine Bourgoin-Voillard, Marta Cascante and Michel Seve
Int. J. Mol. Sci. 2021, 22(7), 3378; https://doi.org/10.3390/ijms22073378 - 25 Mar 2021
Cited by 4 | Viewed by 3183
Abstract
Growing evidence is showing that acetylation plays an essential role in cancer, but studies on the impact of KDAC inhibition (KDACi) on the metabolic profile are still in their infancy. Here, we analyzed, by using an iTRAQ-based quantitative proteomics approach, the changes in [...] Read more.
Growing evidence is showing that acetylation plays an essential role in cancer, but studies on the impact of KDAC inhibition (KDACi) on the metabolic profile are still in their infancy. Here, we analyzed, by using an iTRAQ-based quantitative proteomics approach, the changes in the proteome of KRAS-mutated non-small cell lung cancer (NSCLC) A549 cells in response to trichostatin-A (TSA) and nicotinamide (NAM) under normoxia and hypoxia. Part of this response was further validated by molecular and biochemical analyses and correlated with the proliferation rates, apoptotic cell death, and activation of ROS scavenging mechanisms in opposition to the ROS production. Despite the differences among the KDAC inhibitors, up-regulation of glycolysis, TCA cycle, oxidative phosphorylation and fatty acid synthesis emerged as a common metabolic response underlying KDACi. We also observed that some of the KDACi effects at metabolic levels are enhanced under hypoxia. Furthermore, we used a drug repositioning machine learning approach to list candidate metabolic therapeutic agents for KRAS mutated NSCLC. Together, these results allow us to better understand the metabolic regulations underlying KDACi in NSCLC, taking into account the microenvironment of tumors related to hypoxia, and bring new insights for the future rational design of new therapies. Full article
(This article belongs to the Special Issue Recent Advances of Proteomics Applied to Cancer and Human Diseases)
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17 pages, 2890 KiB  
Article
Proteomic Study Identifies Glycolytic and Inflammation Pathways Involved in Recurrent Otitis Media
by Blendi Ura, Fulvio Celsi, Luisa Zupin, Giorgio Arrigoni, Ilaria Battisti, Bartolomea Gaita, Domenico Leonardo Grasso, Eva Orzan, Raffaella Sagredini, Egidio Barbi and Sergio Crovella
Int. J. Mol. Sci. 2020, 21(23), 9291; https://doi.org/10.3390/ijms21239291 - 05 Dec 2020
Cited by 3 | Viewed by 1764
Abstract
Recurrent acute otitis media (RAOM) in children is clinically defined as the occurrence of at least three episodes of acute otitis media over a course of 6 months. A further common pathological condition of interest in the context of pediatric otolaryngology is adenotonsillar [...] Read more.
Recurrent acute otitis media (RAOM) in children is clinically defined as the occurrence of at least three episodes of acute otitis media over a course of 6 months. A further common pathological condition of interest in the context of pediatric otolaryngology is adenotonsillar hypertrophy (ATH), a common cause of obstructive sleep apnea syndrome. Aimed at unraveling the differential modulation of proteins in the two pathologies and at understanding the possible pathways involved in their onset, we analyzed the proteomic profile of the adenoids from 14 RAOM and ATH patients by using two-dimensional gel electrophoresis (2-DE) and mass spectrometry (MS). The 2-DE coupled with MS allowed us to identify 23 spots with significant (p-value < 0.05) changes in protein amount, recognizing proteins involved in neutrophil degranulation and glycolysis pathways. Full article
(This article belongs to the Special Issue Recent Advances of Proteomics Applied to Cancer and Human Diseases)
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15 pages, 1853 KiB  
Article
Label-Free Mass Spectrometry-Based Quantification of Linker Histone H1 Variants in Clinical Samples
by Roberta Noberini, Cristina Morales Torres, Evelyn Oliva Savoia, Stefania Brandini, Maria Giovanna Jodice, Giovanni Bertalot, Giuseppina Bonizzi, Maria Capra, Giuseppe Diaferia, Paola Scaffidi and Tiziana Bonaldi
Int. J. Mol. Sci. 2020, 21(19), 7330; https://doi.org/10.3390/ijms21197330 - 04 Oct 2020
Cited by 8 | Viewed by 2899
Abstract
Epigenetic aberrations have been recognized as important contributors to cancer onset and development, and increasing evidence suggests that linker histone H1 variants may serve as biomarkers useful for patient stratification, as well as play an important role as drivers in cancer. Although traditionally [...] Read more.
Epigenetic aberrations have been recognized as important contributors to cancer onset and development, and increasing evidence suggests that linker histone H1 variants may serve as biomarkers useful for patient stratification, as well as play an important role as drivers in cancer. Although traditionally histone H1 levels have been studied using antibody-based methods and RNA expression, these approaches suffer from limitations. Mass spectrometry (MS)-based proteomics represents the ideal tool to accurately quantify relative changes in protein abundance within complex samples. In this study, we used a label-free quantification approach to simultaneously analyze all somatic histone H1 variants in clinical samples and verified its applicability to laser micro-dissected tissue areas containing as low as 1000 cells. We then applied it to breast cancer patient samples, identifying differences in linker histone variants patters in primary triple-negative breast tumors with and without relapse after chemotherapy. This study highlights how label-free quantitation by MS is a valuable option to accurately quantitate histone H1 levels in different types of clinical samples, including very low-abundance patient tissues. Full article
(This article belongs to the Special Issue Recent Advances of Proteomics Applied to Cancer and Human Diseases)
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14 pages, 2442 KiB  
Article
Dysregulation of Key Proteins Associated with Sperm Motility and Fertility Potential in Cancer Patients
by Manesh Kumar Panner Selvam, Renata Finelli, Saradha Baskaran and Ashok Agarwal
Int. J. Mol. Sci. 2020, 21(18), 6754; https://doi.org/10.3390/ijms21186754 - 15 Sep 2020
Cited by 10 | Viewed by 2424
Abstract
Cancer has adverse effects on male reproductive health. Conventional semen analysis does not explain the molecular changes in the spermatozoa of cancer patients. Currently, proteomics is being widely used to identify the fertility-associated molecular pathways affected in spermatozoa. The objective of this study [...] Read more.
Cancer has adverse effects on male reproductive health. Conventional semen analysis does not explain the molecular changes in the spermatozoa of cancer patients. Currently, proteomics is being widely used to identify the fertility-associated molecular pathways affected in spermatozoa. The objective of this study was to evaluate the sperm proteome of patients with various types of cancer. Cryopreserved semen samples from patients (testicular cancer, n = 40; Hodgkin’s disease, n = 32; lymphoma, n = 20; leukemia, n = 17) before starting therapy were used for proteomic analysis, while samples from fertile donors (n = 19) were included as controls. The proteomic profiling of sperm was carried out by liquid chromatography-tandem mass spectrometry, and differentially expressed proteins involved in the reproductive processes were validated by Western blotting. Bioinformatic analysis revealed that proteins associated with mitochondrial dysfunction, oxidative phosphorylation, and Sirtuin signaling pathways were dysregulated in cancer patients, while oxidative phosphorylation and tricarboxylic acid cycle were predicted to be deactivated. Furthermore, the analysis revealed dysregulation of key proteins associated with sperm fertility potential and motility (NADH:Ubiquinone oxidoreductase core subunit S1, superoxide dismutase 1, SERPINA5, and cytochrome b-c1 complex subunit 2) in the cancer group, which were further validated by Western blot. Dysfunctional molecular mechanisms essential for fertility in cancer patients prior to therapy highlight the potential impact of cancer phenotype on male fertility. Full article
(This article belongs to the Special Issue Recent Advances of Proteomics Applied to Cancer and Human Diseases)
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12 pages, 1810 KiB  
Article
FACS-Based Proteomics Enables Profiling of Proteins in Rare Cell Populations
by Evelyne Maes, Nathalie Cools, Hanny Willems and Geert Baggerman
Int. J. Mol. Sci. 2020, 21(18), 6557; https://doi.org/10.3390/ijms21186557 - 08 Sep 2020
Cited by 10 | Viewed by 2850
Abstract
Understanding disease pathology often does not require an overall proteomic analysis of clinical samples but rather the analysis of different, often rare, subpopulations of cells in a heterogeneous mixture of cell types. For the isolation of pre-specified cellular subtypes, fluorescence activated cell sorting [...] Read more.
Understanding disease pathology often does not require an overall proteomic analysis of clinical samples but rather the analysis of different, often rare, subpopulations of cells in a heterogeneous mixture of cell types. For the isolation of pre-specified cellular subtypes, fluorescence activated cell sorting (FACS) is commonly used for its ability to isolate the required cell populations with high purity, even of scarce cell types. The proteomic analysis of a limited number of FACS-sorted cells, however, is very challenging as both sample preparation inefficiencies and limits in terms of instrument sensitivity are present. In this study, we used CD14+CD15+ immune cells sorted out of peripheral blood mononuclear cells isolated from whole blood to improve and evaluate FACS-based proteomics. To optimize both the protein extraction protocol and the mass spectrometry (MS) data acquisition method, PBMCs as well as commercialized HeLa digest were used. To reflect the limited number of sorted cells in some clinical samples, different numbers of sorted cells (1000, 5000, 10,000, or 50,000) were used. This allowed comparing protein profiles across samples with limited protein material and provided further insights in the benefits and limitations of using a very limited numbers of cells. Full article
(This article belongs to the Special Issue Recent Advances of Proteomics Applied to Cancer and Human Diseases)
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16 pages, 3631 KiB  
Article
Characterizing the Relapse Potential in Different Luminal Subtypes of Breast Cancers with Functional Proteomics
by Tung-Yi Lin, Pei-Wen Wang, Chun-Hsun Huang, Pei-Ming Yang and Tai-Long Pan
Int. J. Mol. Sci. 2020, 21(17), 6077; https://doi.org/10.3390/ijms21176077 - 24 Aug 2020
Cited by 22 | Viewed by 2487
Abstract
Poor prognosis due to the high relapse and metastasis rates of breast cancer has been particularly linked to the luminal B subtype. The current study utilized MCF-7 and ZR-75-1 to investigate various luminal subtypes of breast cancers that have discrepant expressions in the [...] Read more.
Poor prognosis due to the high relapse and metastasis rates of breast cancer has been particularly linked to the luminal B subtype. The current study utilized MCF-7 and ZR-75-1 to investigate various luminal subtypes of breast cancers that have discrepant expressions in the estrogen receptor (ER) and human epidermal growth factor receptor 2 (HER2). Understanding of the differential protein profiles and the associated pathways could help alleviate the malignance and promote the long-term survival rate of breast cancer patients. Functional proteome tools were applied to comprehensively delineate the global protein alterations that reflect the varieties of biological features between the two subtypes. In this study, a total of 11 proteins with significant and meaningful changes were identified. These protein targets including PRX2, CK19, nucleophosmin and cathepsin D were mostly involved in cell differentiation or proliferation. Particularly, cathepsin D was highly expressed in the luminal B subtype. Moreover, the level of cathepsin-D was also upregulated in the clinical metastatic tissues. Accordingly, the RNA interference-mediated silencing of cathepsin D stimulated ER expression but suppressed the level of HER2. The knockdown of cathepsin D enhanced the level of ZO-1 and a remarkable decrease in N-cadherin was also detected. Again, the matrix metalloproteinases (MMP) activity was impaired under the cathepsin D abolishment. Collectively, this study represented a modality to explore novel relationships in a proteome complex and highlighted the functional roles of cathepsin D in treatment options for different subtypes of breast cancer. Full article
(This article belongs to the Special Issue Recent Advances of Proteomics Applied to Cancer and Human Diseases)
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22 pages, 2747 KiB  
Article
(Phospho)proteomic Profiling of Microsatellite Unstable CRC Cells Reveals Alterations in Nuclear Signaling and Cholesterol Metabolism Caused by Frameshift Mutation of NMD Regulator UPF3A
by Malwina Michalak, Eva-Maria Katzenmaier, Nina Roeckel, Stefan M. Woerner, Vera Fuchs, Uwe Warnken, Yan P. Yuan, Peer Bork, Gabriele Neu-Yilik, Andreas Kulozik, Magnus von Knebel Doeberitz, Matthias Kloor, Jürgen Kopitz and Johannes Gebert
Int. J. Mol. Sci. 2020, 21(15), 5234; https://doi.org/10.3390/ijms21155234 - 23 Jul 2020
Cited by 4 | Viewed by 3304
Abstract
DNA mismatch repair-deficient colorectal cancers (CRCs) accumulate numerous frameshift mutations at repetitive sequences recognized as microsatellite instability (MSI). When coding mononucleotide repeats (cMNRs) are affected, tumors accumulate frameshift mutations and premature termination codons (PTC) potentially leading to truncated proteins. Nonsense-mediated RNA decay (NMD) [...] Read more.
DNA mismatch repair-deficient colorectal cancers (CRCs) accumulate numerous frameshift mutations at repetitive sequences recognized as microsatellite instability (MSI). When coding mononucleotide repeats (cMNRs) are affected, tumors accumulate frameshift mutations and premature termination codons (PTC) potentially leading to truncated proteins. Nonsense-mediated RNA decay (NMD) can degrade PTC-containing transcripts and protect from such faulty proteins. As it also regulates normal transcripts and cellular physiology, we tested whether NMD genes themselves are targets of MSI frameshift mutations. A high frequency of cMNR frameshift mutations in the UPF3A gene was found in MSI CRC cell lines (67.7%), MSI colorectal adenomas (55%) and carcinomas (63%). In normal colonic crypts, UPF3A expression was restricted to single chromogranin A-positive cells. SILAC-based proteomic analysis of KM12 CRC cells revealed UPF3A-dependent down-regulation of several enzymes involved in cholesterol biosynthesis. Furthermore, reconstituted UPF3A expression caused alterations of 85 phosphosites in 52 phosphoproteins. Most of them (38/52, 73%) reside in nuclear phosphoproteins involved in regulation of gene expression and RNA splicing. Since UPF3A mutations can modulate the (phospho)proteomic signature and expression of enzymes involved in cholesterol metabolism in CRC cells, UPF3A may influence other processes than NMD and loss of UPF3A expression might provide a growth advantage to MSI CRC cells. Full article
(This article belongs to the Special Issue Recent Advances of Proteomics Applied to Cancer and Human Diseases)
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16 pages, 2226 KiB  
Article
Selectively-Packaged Proteins in Breast Cancer Extracellular Vesicles Involved in Metastasis
by Penelope V. Dalla, Jerran Santos, Bruce K. Milthorpe and Matthew P. Padula
Int. J. Mol. Sci. 2020, 21(14), 4990; https://doi.org/10.3390/ijms21144990 - 15 Jul 2020
Cited by 15 | Viewed by 2695
Abstract
Cancer-derived extracellular vesicles are known to play a role in the progression of the disease. In this rapidly-growing field, there are many reports of phenotypic changes in cells following exposure to cancer-derived extracellular vesicles. This study examines the protein contents of vesicles derived [...] Read more.
Cancer-derived extracellular vesicles are known to play a role in the progression of the disease. In this rapidly-growing field, there are many reports of phenotypic changes in cells following exposure to cancer-derived extracellular vesicles. This study examines the protein contents of vesicles derived from three well-known breast cancer cell lines, MCF-7, MDA-MB-231 and T47D, using peptide-centric LC-MS/MS and cytokine multiplex immunoassay analysis to understand the molecular basis of these changes. Through these techniques a large number of proteins within these vesicles were identified. A large proportion of these proteins are known to be important in cancer formation and progression and associated with cancer signaling, angiogenesis, metastasis and invasion and immune regulation. This highlights the importance of extracellular vesicles (EVs) in cancer communications and shows some of the mechanisms the vesicles use to assist in cancer progression. Full article
(This article belongs to the Special Issue Recent Advances of Proteomics Applied to Cancer and Human Diseases)
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10 pages, 1103 KiB  
Article
Distinct Proteomic Profile of Spermatozoa from Men with Seminomatous and Non-Seminomatous Testicular Germ Cell Tumors
by Manesh Kumar Panner Selvam, Marco G. Alves, Tânia R. Dias, Peter N. Pushparaj and Ashok Agarwal
Int. J. Mol. Sci. 2020, 21(14), 4817; https://doi.org/10.3390/ijms21144817 - 08 Jul 2020
Cited by 4 | Viewed by 2233
Abstract
Testicular germ cell tumors (TGCTs) are predominant in young males (15–44 years). Seminomatous and non-seminomatous TGCTs account for about 98% of all TGCTs cases. In this study, we aimed to compare the sperm proteome of patients with seminomatous and non-seminomatous TGCTs to identify [...] Read more.
Testicular germ cell tumors (TGCTs) are predominant in young males (15–44 years). Seminomatous and non-seminomatous TGCTs account for about 98% of all TGCTs cases. In this study, we aimed to compare the sperm proteome of patients with seminomatous and non-seminomatous TGCTs to identify possible protein biomarkers that could help distinguish between them in a non-invasive manner. We analyzed semen samples from patients with seminomatous or non-seminomatous TGCTs (n = 15/group) that were cryopreserved before the start of cancer treatment. Quantitative proteomic analysis was conducted on pooled samples (n = 3/group) and a total of 258 differentially expressed proteins (DEPs) were identified. The overexpression of acrosin precursor (ACR) and chaperonin containing TCP1 subunit 6B (CCT6B) as well as the underexpression of S100 calcium-binding protein A9 (S100A9) in the spermatozoa of patients with non-seminomatous TGCTs were validated by western blotting conducted on individual samples (n = 6 for seminomatous group and n = 6 for non-seminomatous group). Our overall results suggest an association between the higher and faster invasiveness of non-seminomatous TGCTs and the altered protein expressions, providing important information for future studies. Full article
(This article belongs to the Special Issue Recent Advances of Proteomics Applied to Cancer and Human Diseases)
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13 pages, 1602 KiB  
Article
Detection of Podocin in Human Urine Sediment Samples by Charge Derivatization and LC-MS-MRM Method
by Remigiusz Bąchor, Dorota Gąszczyk, Karolina Panek-Laszczyńska, Andrzej Konieczny, Wojciech Witkiewicz, Piotr Stefanowicz and Zbigniew Szewczuk
Int. J. Mol. Sci. 2020, 21(9), 3225; https://doi.org/10.3390/ijms21093225 - 02 May 2020
Cited by 6 | Viewed by 2329
Abstract
Detection of podocytes in urine might serve as a useful diagnostic tool in both primary and secondary glomerular diseases. The utility of podocyturia has been confirmed for both pre-eclampsia and glomerulonephritis. Here, we present a new and sensitive method for qualitative LC-MS-multiple-reaction-monitoring (MRM) [...] Read more.
Detection of podocytes in urine might serve as a useful diagnostic tool in both primary and secondary glomerular diseases. The utility of podocyturia has been confirmed for both pre-eclampsia and glomerulonephritis. Here, we present a new and sensitive method for qualitative LC-MS-multiple-reaction-monitoring (MRM) analysis of podocin, serving as a podocyturia biomarker in urine sediments. The following podocin tryptic peptides with the 169LQTLEIPFHEIVTK182, 213AVQFLVQTTMK223, 240SIAQDAK246, and 292MIAAEAEK299 sequences were applied as a model. The selective chemical derivatization of the ε amino group of C-terminal lysine residue in tryptic peptides, by 2,4,6-triphenylpyrylium salt (TPP) as a fixed charge tag, was employed to increase the ionization efficiency, in routine ESI-MS analysis. Additionally, the generation of a reporter ion, in the form of a protonated 2,4,6-triphenylpyridinium cation, makes the derivatized peptide analysis in the MRM mode unambiguous. Identification of derivatized and non-derivatized peptides were performed, and the obtained results suggest that the peptide with the 292MIAAEAEK299 sequence may serve as a marker of podocyturia. Full article
(This article belongs to the Special Issue Recent Advances of Proteomics Applied to Cancer and Human Diseases)
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17 pages, 3706 KiB  
Article
Proteomic Profiling of Colon Cancer Tissues: Discovery of New Candidate Biomarkers
by Miriam Buttacavoli, Nadia Ninfa Albanese, Elena Roz, Ida Pucci-Minafra, Salvatore Feo and Patrizia Cancemi
Int. J. Mol. Sci. 2020, 21(9), 3096; https://doi.org/10.3390/ijms21093096 - 28 Apr 2020
Cited by 15 | Viewed by 3328
Abstract
Colon cancer is an aggressive tumor form with a poor prognosis. This study reports a comparative proteomic analysis performed by using two-dimensional differential in-gel electrophoresis (2D-DIGE) between 26 pooled colon cancer surgical tissues and adjacent non-tumoral tissues, to identify potential target proteins correlated [...] Read more.
Colon cancer is an aggressive tumor form with a poor prognosis. This study reports a comparative proteomic analysis performed by using two-dimensional differential in-gel electrophoresis (2D-DIGE) between 26 pooled colon cancer surgical tissues and adjacent non-tumoral tissues, to identify potential target proteins correlated with carcinogenesis. The DAVID functional classification tool revealed that most of the differentially regulated proteins, acting both intracellularly and extracellularly, concur across multiple cancer steps. The identified protein classes include proteins involved in cell proliferation, apoptosis, metabolic pathways, oxidative stress, cell motility, Ras signal transduction, and cytoskeleton. Interestingly, networks and pathways analysis showed that the identified proteins could be biologically inter-connected to the tumor-host microenvironment, including innate immune response, platelet and neutrophil degranulation, and hemostasis. Finally, transgelin (TAGL), here identified for the first time with four different protein species, collectively down-regulated in colon cancer tissues, emerged as a top-ranked biomarker for colorectal cancer (CRC). In conclusion, our findings revealed a different proteomic profiling in colon cancer tissues characterized by the deregulation of specific pathways involved in hallmarks of cancer. All of these proteins may represent promising novel colon cancer biomarkers and potential therapeutic targets, if validated in larger cohorts of patients. Full article
(This article belongs to the Special Issue Recent Advances of Proteomics Applied to Cancer and Human Diseases)
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Review

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16 pages, 1531 KiB  
Review
Clinical Perspective on Proteomic and Glycomic Biomarkers for Diagnosis, Prognosis, and Prediction of Pancreatic Cancer
by Randa G. Hanna-Sawires, Jorinde H. Schiphuis, Manfred Wuhrer, Hans F. A. Vasen, Monique E. van Leerdam, Bert A. Bonsing, Wilma E. Mesker, Yuri E. M. van der Burgt and Rob A. E. M. Tollenaar
Int. J. Mol. Sci. 2021, 22(5), 2655; https://doi.org/10.3390/ijms22052655 - 06 Mar 2021
Cited by 14 | Viewed by 3265
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is known as a highly aggressive malignant disease. Prognosis for patients is notoriously poor, despite improvements in surgical techniques and new (neo)adjuvant chemotherapy regimens. Early detection of PDAC may increase the overall survival. It is furthermore foreseen that precision [...] Read more.
Pancreatic ductal adenocarcinoma (PDAC) is known as a highly aggressive malignant disease. Prognosis for patients is notoriously poor, despite improvements in surgical techniques and new (neo)adjuvant chemotherapy regimens. Early detection of PDAC may increase the overall survival. It is furthermore foreseen that precision medicine will provide improved prognostic stratification and prediction of therapeutic response. In this review, omics-based discovery efforts are presented that aim for novel diagnostic and prognostic biomarkers of PDAC. For this purpose, we systematically evaluated the literature published between 1999 and 2020 with a focus on protein- and protein-glycosylation biomarkers in pancreatic cancer patients. Besides genomic and transcriptomic approaches, mass spectrometry (MS)-based proteomics and glycomics of blood- and tissue-derived samples from PDAC patients have yielded new candidates with biomarker potential. However, for reasons discussed in this review, the validation and clinical translation of these candidate markers has not been successful. Consequently, there has been a change of mindset from initial efforts to identify new unimarkers into the current hypothesis that a combination of biomarkers better suits a diagnostic or prognostic panel. With continuing development of current research methods and available techniques combined with careful study designs, new biomarkers could contribute to improved detection, prognosis, and prediction of pancreatic cancer. Full article
(This article belongs to the Special Issue Recent Advances of Proteomics Applied to Cancer and Human Diseases)
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22 pages, 1945 KiB  
Review
Insights into Bioinformatic Applications for Glycosylation: Instigating an Awakening towards Applying Glycoinformatic Resources for Cancer Diagnosis and Therapy
by Manikandan Muthu, Sechul Chun, Judy Gopal, Vimala Anthonydhason, Steve W. Haga, Anna Jacintha Prameela Devadoss and Jae-Wook Oh
Int. J. Mol. Sci. 2020, 21(24), 9336; https://doi.org/10.3390/ijms21249336 - 08 Dec 2020
Cited by 5 | Viewed by 3064
Abstract
Glycosylation plays a crucial role in various diseases and their etiology. This has led to a clear understanding on the functions of carbohydrates in cell communication, which eventually will result in novel therapeutic approaches for treatment of various disease. Glycomics has now become [...] Read more.
Glycosylation plays a crucial role in various diseases and their etiology. This has led to a clear understanding on the functions of carbohydrates in cell communication, which eventually will result in novel therapeutic approaches for treatment of various disease. Glycomics has now become one among the top ten technologies that will change the future. The direct implication of glycosylation as a hallmark of cancer and for cancer therapy is well established. As in proteomics, where bioinformatics tools have led to revolutionary achievements, bioinformatics resources for glycosylation have improved its practical implication. Bioinformatics tools, algorithms and databases are a mandatory requirement to manage and successfully analyze large amount of glycobiological data generated from glycosylation studies. This review consolidates all the available tools and their applications in glycosylation research. The achievements made through the use of bioinformatics into glycosylation studies are also presented. The importance of glycosylation in cancer diagnosis and therapy is discussed and the gap in the application of widely available glyco-informatic tools for cancer research is highlighted. This review is expected to bring an awakening amongst glyco-informaticians as well as cancer biologists to bridge this gap, to exploit the available glyco-informatic tools for cancer. Full article
(This article belongs to the Special Issue Recent Advances of Proteomics Applied to Cancer and Human Diseases)
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23 pages, 997 KiB  
Review
The Implementation of Mass Spectrometry-Based Proteomics Workflows in Clinical Routines of Acute Myeloid Leukemia: Applicability and Perspectives
by Maria Hernandez-Valladares, Øystein Bruserud and Frode Selheim
Int. J. Mol. Sci. 2020, 21(18), 6830; https://doi.org/10.3390/ijms21186830 - 17 Sep 2020
Cited by 11 | Viewed by 3560
Abstract
With the current reproducibility of proteome preparation workflows along with the speed and sensitivity of the mass spectrometers, the transition of the mass spectrometry (MS)-based proteomics technology from biomarker discovery to clinical implementation is under appraisal in the biomedicine community. Therefore, this technology [...] Read more.
With the current reproducibility of proteome preparation workflows along with the speed and sensitivity of the mass spectrometers, the transition of the mass spectrometry (MS)-based proteomics technology from biomarker discovery to clinical implementation is under appraisal in the biomedicine community. Therefore, this technology might be implemented soon to detect well-known biomarkers in cancers and other diseases. Acute myeloid leukemia (AML) is an aggressive heterogeneous malignancy that requires intensive treatment to cure the patient. Leukemia relapse is still a major challenge even for patients who have favorable genetic abnormalities. MS-based proteomics could be of great help to both describe the proteome changes of individual patients and identify biomarkers that might encourage specific treatments or clinical strategies. Herein, we will review the advances and availability of the MS-based proteomics strategies that could already be used in clinical proteomics. However, the heterogeneity of complex diseases as AML requires consensus to recognize AML biomarkers and to establish MS-based workflows that allow their unbiased identification and quantification. Although our literature review appears promising towards the utilization of MS-based proteomics in clinical AML in a near future, major efforts are required to validate AML biomarkers and agree on clinically approved workflows. Full article
(This article belongs to the Special Issue Recent Advances of Proteomics Applied to Cancer and Human Diseases)
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17 pages, 1113 KiB  
Review
The MUDENG Augmentation: A Genesis in Anti-Cancer Therapy?
by Manikandan Muthu, Sechul Chun, Judy Gopal, Gyun-Seok Park, Arti Nile, Jisoo Shin, Juhyun Shin, Tae-Hyoung Kim and Jae-Wook Oh
Int. J. Mol. Sci. 2020, 21(15), 5583; https://doi.org/10.3390/ijms21155583 - 04 Aug 2020
Cited by 6 | Viewed by 3815
Abstract
Despite multitudes of reports on cancer remedies available, we are far from being able to declare that we have arrived at that defining anti-cancer therapy. In recent decades, researchers have been looking into the possibility of enhancing cell death-related signaling pathways in cancer [...] Read more.
Despite multitudes of reports on cancer remedies available, we are far from being able to declare that we have arrived at that defining anti-cancer therapy. In recent decades, researchers have been looking into the possibility of enhancing cell death-related signaling pathways in cancer cells using pro-apoptotic proteins. Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) and Mu-2/AP1M2 domain containing, death-inducing (MUDENG, MuD) have been established for their ability to bring about cell death specifically in cancer cells. Targeted cell death is a very attractive term when it comes to cancer, since most therapies also affect normal cells. In this direction TRAIL has made noteworthy progress. This review briefly sums up what has been done using TRAIL in cancer therapeutics. The importance of MuD and what has been achieved thus far through MuD and the need to widen and concentrate on applicational aspects of MuD has been highlighted. This has been suggested as the future perspective of MuD towards prospective progress in cancer research. Full article
(This article belongs to the Special Issue Recent Advances of Proteomics Applied to Cancer and Human Diseases)
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