Proteomics in Cancer Research

A special issue of Proteomes (ISSN 2227-7382). This special issue belongs to the section "Proteomics of Human Diseases and Their Treatments".

Deadline for manuscript submissions: closed (31 May 2023) | Viewed by 28793

Special Issue Editor


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Guest Editor
Biochemistry & Proteomics Group, Department of Chemistry and Biomolecular Science, Clarkson University, 8 Clarkson Avenue, Potsdam, NY 13699-5810, USA
Interests: protein–protein interactions and their relation to disease; cell proliferation and differentiation; serum biomarkers for diagnosis and prognosis of cancer and psychiatric problems; analytical biochemistry; protein chemistry; mass spectrometry

Special Issue Information

Dear Colleagues,

In recent years, proteomics has become one of the most important tools that can be used in understanding the behavior of proteins, protein post-translational modifications and protein–protein interactions.

The human genome has been sequenced and it suggests that, with about 30,000 genes, we are not very complicated. Yet, a multi-exon eukaryotic gene can direct the formation of multiple protein isoforms, with multiple subcellular locations, membrane and non-membrane bound, within multiple tissues and organs. One of the best-known examples is tropomyosin, which is different in different organs and tissues (i.e., brain vs. muscle) and can be both membrane-bound or not, depending on the structure of the exon 9 of its gene. Another good example is represented by immunoglobulins G, or antibodies, which can have different isotypes, which are both soluble and membrane-bound isoproteins.

In addition to the formation of multiple isoproteins with multiple functions, our uniqueness also relies on post-translational modifications of these proteins. Some of them are transiently modified, in response to a stimulus (i.e., phosphorylation during activation of receptor tyrosine kinase pathways), while others are sentenced to death by tagging (i.e., ubiquitin tagging). Lastly, the important roles of interactions between our proteins through stable (i.e., protein complexes) and transient (i.e., upon a response to a stimulus) protein–protein interactions force us to understand that proteins, in a protein-centric world, makes us complex, and capable to adapt and evolve to the constantly changing environment. Therefore, the ~30,000 genes which direct the millions and millions of proteins, isoproteins, post-translationally modified proteins, and stable and transient protein–protein interactions make us complicated and capable to adapt and evolve. Changes at the protein level also allow us to identify indicators of cancer, either through early detection or predictions of cancer progression, or even prediction of the body’s response to treatment.  

This Special Issue of Proteomes welcomes submissions of original research or review articles aiming at deciphering physiological processes with the use of proteomics tools. Contributions will deal with the dynamics of proteins in their native and modified forms, with the combination of several “omics” approaches in contrasted physiological situations as well as with technical advances in the proteomic field.

Prof. Dr. Costel C. Darie
Guest Editor

Manuscript Submission Information

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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 1800 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

  • Proteomics
  • Protein post-translational modifications
  • Quantitative proteomics
  • Cancer detection

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Published Papers (8 papers)

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Research

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13 pages, 2245 KiB  
Article
Mass Spectrometry and Pharmacological Approaches to Measuring Cooption and Reciprocal Activation of Receptor Tyrosine Kinases
by Jason Linzer, Zachary Phelps, Shivasuryan Vummidi, Bo Young Elizabeth Lee, Nicolas Coant and John D. Haley
Proteomes 2023, 11(2), 20; https://doi.org/10.3390/proteomes11020020 - 2 Jun 2023
Viewed by 2019
Abstract
Receptor tyrosine kinases (RTKs) can show extensive crosstalk, directly and indirectly. Elucidating RTK crosstalk remains an important goal in the clinical combination of anti-cancer therapies. Here, we present mass spectrometry and pharmacological approaches showing the hepatocyte growth factor receptor (MET)-promoting tyrosine phosphorylation of [...] Read more.
Receptor tyrosine kinases (RTKs) can show extensive crosstalk, directly and indirectly. Elucidating RTK crosstalk remains an important goal in the clinical combination of anti-cancer therapies. Here, we present mass spectrometry and pharmacological approaches showing the hepatocyte growth factor receptor (MET)-promoting tyrosine phosphorylation of the epidermal growth factor receptor (EGFR) and other membrane receptors in MET-amplified H1993 NSCLC cells. Conversely, in H292 wt-EGFR NSCLC cells, EGFR promotes the tyrosine phosphorylation of MET. Reciprocal regulation of the EGFR and insulin receptor (IR) was observed in the GEO CRC cells, where inhibition of the EGFR drives tyrosine phosphorylation of the insulin receptor. Similarly, in platelet-derived growth factor receptor (PDGFR)-amplified H1703 NSCLC cells, inhibition of the EGFR promotes the tyrosine phosphorylation of the PDGFR. These RTK interactions are used to illustrate basic principles applicable to other RTK signaling networks. More specifically, we focus on two types of RTK interaction: (1) co-option of one RTK by another and (2) reciprocal activation of one receptor following the inhibition of a distinct receptor. Full article
(This article belongs to the Special Issue Proteomics in Cancer Research)
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19 pages, 1600 KiB  
Article
A Multi-Level Systems Biology Analysis of Aldrin’s Metabolic Effects on Prostate Cancer Cells
by Carmen Bedia, Nuria Dalmau, Lars K. Nielsen, Romà Tauler and Igor Marín de Mas
Proteomes 2023, 11(2), 11; https://doi.org/10.3390/proteomes11020011 - 23 Mar 2023
Viewed by 2413
Abstract
Although numerous studies support a dose–effect relationship between Endocrine disruptors (EDs) and the progression and malignancy of tumors, the impact of a chronic exposure to non-lethal concentrations of EDs in cancer remains unknown. More specifically, a number of studies have reported the impact [...] Read more.
Although numerous studies support a dose–effect relationship between Endocrine disruptors (EDs) and the progression and malignancy of tumors, the impact of a chronic exposure to non-lethal concentrations of EDs in cancer remains unknown. More specifically, a number of studies have reported the impact of Aldrin on a variety of cancer types, including prostate cancer. In previous studies, we demonstrated the induction of the malignant phenotype in DU145 prostate cancer (PCa) cells after a chronic exposure to Aldrin (an ED). Proteins are pivotal in the regulation and control of a variety of cellular processes. However, the mechanisms responsible for the impact of ED on PCa and the role of proteins in this process are not yet well understood. Here, two complementary computational approaches have been employed to investigate the molecular processes underlying the acquisition of malignancy in prostate cancer. First, the metabolic reprogramming associated with the chronic exposure to Aldrin in DU145 cells was studied by integrating transcriptomics and metabolomics via constraint-based metabolic modeling. Second, gene set enrichment analysis was applied to determine (i) altered regulatory pathways and (ii) the correlation between changes in the transcriptomic profile of Aldrin-exposed cells and tumor progression in various types of cancer. Experimental validation confirmed predictions revealing a disruption in metabolic and regulatory pathways. This alteration results in the modification of protein levels crucial in regulating triacylglyceride/cholesterol, linked to the malignant phenotype observed in Aldrin-exposed cells. Full article
(This article belongs to the Special Issue Proteomics in Cancer Research)
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17 pages, 775 KiB  
Article
Mass Spectrometry-Based Proteomics of Human Milk to Identify Differentially Expressed Proteins in Women with Breast Cancer versus Controls
by Roshanak Aslebagh, Danielle Whitham, Devika Channaveerappa, Panashe Mutsengi, Brian T. Pentecost, Kathleen F. Arcaro and Costel C. Darie
Proteomes 2022, 10(4), 36; https://doi.org/10.3390/proteomes10040036 - 28 Oct 2022
Cited by 10 | Viewed by 3172
Abstract
It is thought that accurate risk assessment and early diagnosis of breast cancer (BC) can help reduce cancer-related mortality. Proteomics analysis of breast milk may provide biomarkers of risk and occult disease. Our group works on the analysis of human milk samples from [...] Read more.
It is thought that accurate risk assessment and early diagnosis of breast cancer (BC) can help reduce cancer-related mortality. Proteomics analysis of breast milk may provide biomarkers of risk and occult disease. Our group works on the analysis of human milk samples from women with BC and controls to investigate alterations in protein patterns of milk that could be related to BC. In the current study, we used mass spectrometry (MS)-based proteomics analysis of 12 milk samples from donors with BC and matched controls. Specifically, we used one-dimensional (1D)-polyacrylamide gel electrophoresis (PAGE) coupled with nanoliquid chromatography tandem MS (nanoLC-MS/MS), followed by bioinformatics analysis. We confirmed the dysregulation of several proteins identified previously in a different set of milk samples. We also identified additional dysregulations in milk proteins shown to play a role in cancer development, such as Lactadherin isoform A, O-linked N-acetylglucosamine (GlcNAc) transferase, galactosyltransferase, recoverin, perilipin-3 isoform 1, histone-lysine methyltransferase, or clathrin heavy chain. Our results expand our current understanding of using milk as a biological fluid for identification of BC-related dysregulated proteins. Overall, our results also indicate that milk has the potential to be used for BC biomarker discovery, early detection and risk assessment in young, reproductively active women. Full article
(This article belongs to the Special Issue Proteomics in Cancer Research)
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Review

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28 pages, 3009 KiB  
Review
Oncogenic Proteomics Approaches for Translational Research and HIV-Associated Malignancy Mechanisms
by Eduardo Alvarez-Rivera, Emanuel J. Ortiz-Hernández, Elyette Lugo, Lorraine M. Lozada-Reyes and Nawal M. Boukli
Proteomes 2023, 11(3), 22; https://doi.org/10.3390/proteomes11030022 - 4 Jul 2023
Viewed by 2842
Abstract
Recent advances in the field of proteomics have allowed extensive insights into the molecular regulations of the cell proteome. Specifically, this allows researchers to dissect a multitude of signaling arrays while targeting for the discovery of novel protein signatures. These approaches based on [...] Read more.
Recent advances in the field of proteomics have allowed extensive insights into the molecular regulations of the cell proteome. Specifically, this allows researchers to dissect a multitude of signaling arrays while targeting for the discovery of novel protein signatures. These approaches based on data mining are becoming increasingly powerful for identifying both potential disease mechanisms as well as indicators for disease progression and overall survival predictive and prognostic molecular markers for cancer. Furthermore, mass spectrometry (MS) integrations satisfy the ongoing demand for in-depth biomarker validation. For the purpose of this review, we will highlight the current developments based on MS sensitivity, to place quantitative proteomics into clinical settings and provide a perspective to integrate proteomics data for future applications in cancer precision medicine. We will also discuss malignancies associated with oncogenic viruses such as Acquire Immunodeficiency Syndrome (AIDS) and suggest novel mechanisms behind this phenomenon. Human Immunodeficiency Virus type-1 (HIV-1) proteins are known to be oncogenic per se, to induce oxidative and endoplasmic reticulum stresses, and to be released from the infected or expressing cells. HIV-1 proteins can act alone or in collaboration with other known oncoproteins, which cause the bulk of malignancies in people living with HIV-1 on ART. Full article
(This article belongs to the Special Issue Proteomics in Cancer Research)
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25 pages, 791 KiB  
Review
Proteomics-Based Identification of Dysregulated Proteins and Biomarker Discovery in Invasive Ductal Carcinoma, the Most Common Breast Cancer Subtype
by Anca-Narcisa Neagu, Danielle Whitham, Logan Seymour, Norman Haaker, Isabella Pelkey and Costel C. Darie
Proteomes 2023, 11(2), 13; https://doi.org/10.3390/proteomes11020013 - 3 Apr 2023
Cited by 7 | Viewed by 4460
Abstract
Invasive ductal carcinoma (IDC) is the most common histological subtype of malignant breast cancer (BC), and accounts for 70–80% of all invasive BCs. IDC demonstrates great heterogeneity in clinical and histopathological characteristics, prognoses, treatment strategies, gene expressions, and proteomic profiles. Significant proteomic determinants [...] Read more.
Invasive ductal carcinoma (IDC) is the most common histological subtype of malignant breast cancer (BC), and accounts for 70–80% of all invasive BCs. IDC demonstrates great heterogeneity in clinical and histopathological characteristics, prognoses, treatment strategies, gene expressions, and proteomic profiles. Significant proteomic determinants of the progression from intraductal pre-invasive malignant lesions of the breast, which characterize a ductal carcinoma in situ (DCIS), to IDC, are still poorly identified, validated, and clinically applied. In the era of “6P” medicine, it remains a great challenge to determine which patients should be over-treated versus which need to be actively monitored without aggressive treatment. The major difficulties for designating DCIS to IDC progression may be solved by understanding the integrated genomic, transcriptomic, and proteomic bases of invasion. In this review, we showed that multiple proteomics-based techniques, such as LC–MS/MS, MALDI-ToF MS, SELDI-ToF-MS, MALDI-ToF/ToF MS, MALDI-MSI or MasSpec Pen, applied to in-tissue, off-tissue, BC cell lines and liquid biopsies, improve the diagnosis of IDC, as well as its prognosis and treatment monitoring. Classic proteomics strategies that allow the identification of dysregulated protein expressions, biological processes, and interrelated pathway analyses based on aberrant protein–protein interaction (PPI) networks have been improved to perform non-invasive/minimally invasive biomarker detection of early-stage IDC. Thus, in modern surgical oncology, highly sensitive, rapid, and accurate MS-based detection has been coupled with “proteome point sampling” methods that allow for proteomic profiling by in vivo “proteome point characterization”, or by minimal tissue removal, for ex vivo accurate differentiation and delimitation of IDC. For the detection of low-molecular-weight proteins and protein fragments in bodily fluids, LC–MS/MS and MALDI-MS techniques may be coupled to enrich and capture methods which allow for the identification of early-stage IDC protein biomarkers that were previously invisible for MS-based techniques. Moreover, the detection and characterization of protein isoforms, including posttranslational modifications of proteins (PTMs), is also essential to emphasize specific molecular mechanisms, and to assure the early-stage detection of IDC of the breast. Full article
(This article belongs to the Special Issue Proteomics in Cancer Research)
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14 pages, 1032 KiB  
Review
The Double-Edged Proteins in Cancer Proteomes and the Generation of Induced Tumor-Suppressing Cells (iTSCs)
by Kexin Li, Qingji Huo, Bai-Yan Li and Hiroki Yokota
Proteomes 2023, 11(1), 5; https://doi.org/10.3390/proteomes11010005 - 18 Jan 2023
Cited by 3 | Viewed by 2563
Abstract
Unlike a prevalent expectation that tumor cells secrete tumor-promoting proteins and stimulate the progression of neighboring tumor cells, accumulating evidence indicates that the role of tumor-secreted proteins is double-edged and context-dependent. Some of the oncogenic proteins in the cytoplasm and cell membranes, which [...] Read more.
Unlike a prevalent expectation that tumor cells secrete tumor-promoting proteins and stimulate the progression of neighboring tumor cells, accumulating evidence indicates that the role of tumor-secreted proteins is double-edged and context-dependent. Some of the oncogenic proteins in the cytoplasm and cell membranes, which are considered to promote the proliferation and migration of tumor cells, may inversely act as tumor-suppressing proteins in the extracellular domain. Furthermore, the action of tumor-secreted proteins by aggressive “super-fit” tumor cells can be different from those derived from “less-fit” tumor cells. Tumor cells that are exposed to chemotherapeutic agents could alter their secretory proteomes. Super-fit tumor cells tend to secrete tumor-suppressing proteins, while less-fit or chemotherapeutic agent-treated tumor cells may secrete tumor-promotive proteomes. Interestingly, proteomes derived from nontumor cells such as mesenchymal stem cells and peripheral blood mononuclear cells mostly share common features with tumor cell-derived proteomes in response to certain signals. This review introduces the double-sided functions of tumor-secreted proteins and describes the proposed underlying mechanism, which would possibly be based on cell competition. Full article
(This article belongs to the Special Issue Proteomics in Cancer Research)
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12 pages, 1185 KiB  
Review
Salivary Biomarkers in Oral Squamous Cell Carcinoma: A Proteomic Overview
by Gabriele Riccardi, Mario Giuseppe Bellizzi, Irene Fatuzzo, Federica Zoccali, Luca Cavalcanti, Antonio Greco, Marco de Vincentiis, Massimo Ralli, Marco Fiore, Carla Petrella, Antonio Minni and Christian Barbato
Proteomes 2022, 10(4), 37; https://doi.org/10.3390/proteomes10040037 - 7 Nov 2022
Cited by 23 | Viewed by 4549
Abstract
Background: Oral squamous cell carcinoma (OSCC) is one of the most frequent cancers worldwide. Endoscopic methods may be useful in the evaluation of oral injuries even though the diagnostic gold standard is a biopsy. Targeted screenings could be considered the best way to [...] Read more.
Background: Oral squamous cell carcinoma (OSCC) is one of the most frequent cancers worldwide. Endoscopic methods may be useful in the evaluation of oral injuries even though the diagnostic gold standard is a biopsy. Targeted screenings could be considered the best way to prevent the occurrence of oral cancer. Aimed to elucidate the potential identification of specific biomarkers of OSCC, the use of saliva is convenient and noninvasive. Many studies reported more than a hundred putative saliva biomarkers for OSCC, and proteogenomic approaches were fundamental to disclosing this issue. Methods: Relevant literature published in the last few years was systematically searched on PubMed and we focused on articles about the use and study of salivary biomarkers in the diagnostics of head and neck cancer (n = 110). Thereafter, we performed a selection focusing on diagnosis with salivary proteomics in OSCC (n = 8). Results: Saliva proteomics can be a source of biomarkers for OSCC. We reviewed literature of biomarker proteins in saliva that could also be evaluated as probable targets for non-invasive screening of oral neoplasm such as cytokines, matrix metalloproteinases, and acute-phase response proteins. Conclusions: The measurement of salivary biomarkers is a highly hopeful technique for the diagnosis of OSCC. Proteogenomic approaches could permit an accurate and early diagnosis of OSCC. This review seeks to generate an up-to-date view on translational OSCC issues by raising awareness of researchers, physicians, and surgeons. Renewed clinical studies, which will validate the sensitivity and specificity of salivary biomarkers, are necessary to translate these results into possible strategies for early diagnosis of OSCC, thus improving patient outcomes. Full article
(This article belongs to the Special Issue Proteomics in Cancer Research)
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28 pages, 1899 KiB  
Review
Proteomics-Based Identification of Dysregulated Proteins in Breast Cancer
by Anca-Narcisa Neagu, Madhuri Jayathirtha, Danielle Whitham, Panashe Mutsengi, Isabelle Sullivan, Brindusa Alina Petre and Costel C. Darie
Proteomes 2022, 10(4), 35; https://doi.org/10.3390/proteomes10040035 - 21 Oct 2022
Cited by 13 | Viewed by 5133
Abstract
Immunohistochemistry (IHC) is still widely used as a morphology-based assay for in situ analysis of target proteins as specific tumor antigens. However, as a very heterogeneous collection of neoplastic diseases, breast cancer (BC) requires an accurate identification and characterization of larger panels of [...] Read more.
Immunohistochemistry (IHC) is still widely used as a morphology-based assay for in situ analysis of target proteins as specific tumor antigens. However, as a very heterogeneous collection of neoplastic diseases, breast cancer (BC) requires an accurate identification and characterization of larger panels of candidate biomarkers, beyond ER, PR, and HER2 proteins, for diagnosis and personalized treatment, without the limited availability of antibodies that are required to identify specific proteins. Top-down, middle-down, and bottom-up mass spectrometry (MS)-based proteomics approaches complement traditional histopathological tissue analysis to examine expression, modification, and interaction of hundreds to thousands of proteins simultaneously. In this review, we discuss the proteomics-based identification of dysregulated proteins in BC that are essential for the following issues: discovery and validation of new biomarkers by analysis of solid and liquid/non-invasive biopsies, cell lines, organoids and xenograft models; identification of panels of biomarkers for early detection and accurate discrimination between cancer, benign and normal tissues; identification of subtype-specific and stage-specific protein expression profiles in BC grading and measurement of disease progression; characterization of new subtypes of BC; characterization and quantitation of post-translational modifications (PTMs) and aberrant protein–protein interactions (PPI) involved in tumor development; characterization of the global remodeling of BC tissue homeostasis, diagnosis and prognostic information; and deciphering of molecular functions, biological processes and mechanisms through which the dysregulated proteins cause tumor initiation, invasion, and treatment resistance. Full article
(This article belongs to the Special Issue Proteomics in Cancer Research)
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