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Cancers
Special Issues
Clinical Proteomics in Proliferative Disorders
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Clinical Proteomics in Proliferative Disorders

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Biomarkers".

Deadline for manuscript submissions: closed (30 March 2022) | Viewed by 12728

Special Issue Editors

Dr. Attila Marcell Szász

E-Mail Website
Guest Editor
Division of Oncology, Department of Internal Medicine and Oncology, Semmelweis University, 1083 Budapest, Hungary
Interests: pathology; oncology; solid tumors; clinical trials; prognosis; prediction
Dr. György Marko-Varga

E-Mail Website
Guest Editor
Department of Biomedical, Engineering, Lund University, 22100 Lund, Sweden
Interests: analytic chemistry; proteomics; biobanking; sample processing

Special Issue Information

Dear Colleagues,

Neoplastic and non-neoplastic disorders of human pathology encompass a wide spectrum of disease states with various prognostics. Our ultimate goal is to discover and implement diagnostic and therapeutic tools to improve outcomes and the life quality of patients. A stratification that guides appropriate interventions has been coveted since medicine was first invented. In recent decades, we have witnessed the advent of transcriptomics and genomics which today are the cornerstones of clinical decision making in modern molecularly driven therapeutics. Proteomics will bridge the gap between genetics and the resulting phenotypes, which will also improve our understanding of human diseases like never before. Clinical practice and adaptation of new discoveries in routine operations have never been more straightforward.

In this Special Issue, we seek contributions which improve our understanding of tumor biology or non-neoplastic proliferative disorders with a direct implication for patient care. Results of measurements performed on human tissue or clinical data are encouraged. Original reports, review articles, meta-analyses, and clinical trial reports which contain protein-level investigation with direct implication in patient care are also welcome.

Dr. Attila Marcell Szász
Prof. Dr. György Marko-Varga
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. Cancers is an international peer-reviewed open access semimonthly 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 2900 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
  • bioinformatics
  • clinical implementation
  • solid tumors

Published Papers (5 papers)

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Research

17 pages, 3685 KiB  
Article
Circulating SOD2 Is a Candidate Response Biomarker for Neoadjuvant Therapy in Breast Cancer
by Mercè Juliachs, Mireia Pujals, Chiara Bellio, Nathalie Meo-Evoli, Juan M. Duran, Esther Zamora, Mireia Parés, Anna Suñol, Olga Méndez, Alex Sánchez-Pla, Francesc Canals, Cristina Saura and Josep Villanueva
Cancers 2022, 14(16), 3858; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14163858 - 10 Aug 2022
Cited by 2 | Viewed by 1981
Abstract
There is a great need for non-invasive tools that inform of an early molecular response to cancer therapeutic treatment. Here, we tested the hypothesis that proteolytically resistant proteins could be candidate circulating tumor biomarkers for cancer therapy. Proteins resistant to proteolysis are drastically [...] Read more.
There is a great need for non-invasive tools that inform of an early molecular response to cancer therapeutic treatment. Here, we tested the hypothesis that proteolytically resistant proteins could be candidate circulating tumor biomarkers for cancer therapy. Proteins resistant to proteolysis are drastically under-sampled by current proteomic workflows. These proteins could be reliable sensors for the response to therapy since they are likely to stay longer in circulation. We selected manganese superoxide dismutase (SOD2), a mitochondrial redox enzyme, from a screening of proteolytic resistant proteins in breast cancer (BC). First, we confirmed the robustness of SOD2 and determined that its proteolytic resistance is mediated by its quaternary protein structure. We also proved that the release of SOD2 upon chemotherapy treatment correlates with cell death in BC cells. Then, after confirming that SOD2 is very stable in human serum, we sought to measure its circulating levels in a cohort of BC patients undergoing neoadjuvant therapy. The results showed that circulating levels of SOD2 increased when patients responded to the treatment according to the tumor shrinkage during neoadjuvant chemotherapy. Therefore, the measurement of SOD2 levels in plasma could improve the non-invasive monitoring of the therapeutic treatment in breast cancer patients. The identification of circulating biomarkers linked to the tumor cell death induced by treatment could be useful for monitoring the action of the large number of cancer drugs currently used in clinics. We envision that our approach could help uncover candidate tumor biomarkers to measure a tumor’s response to cancer therapy in real time by sampling the tumor throughout the course of treatment. Full article
(This article belongs to the Special Issue Clinical Proteomics in Proliferative Disorders)
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19 pages, 3120 KiB  
Article
Proteomic Analysis of Lung Cancer Types—A Pilot Study
by Simon Sugár, Fanni Bugyi, Gábor Tóth, Judit Pápay, Ilona Kovalszky, Tamás Tornóczky, László Drahos and Lilla Turiák
Cancers 2022, 14(11), 2629; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14112629 - 26 May 2022
Cited by 7 | Viewed by 2289
Abstract
Lung cancer is the leading cause of tumor-related mortality, therefore significant effort is directed towards understanding molecular alterations occurring at the origin of the disease to improve current treatment options. The aim of our pilot-scale study was to carry out a detailed proteomic [...] Read more.
Lung cancer is the leading cause of tumor-related mortality, therefore significant effort is directed towards understanding molecular alterations occurring at the origin of the disease to improve current treatment options. The aim of our pilot-scale study was to carry out a detailed proteomic analysis of formalin-fixed paraffin-embedded tissue sections from patients with small cell or non-small cell lung cancer (adenocarcinoma, squamous cell carcinoma, and large cell carcinoma). Tissue surface digestion was performed on relatively small cancerous and tumor-adjacent normal regions and differentially expressed proteins were identified using label-free quantitative mass spectrometry and subsequent statistical analysis. Principal component analysis clearly distinguished cancerous and cancer adjacent normal samples, while the four lung cancer types investigated had distinct molecular profiles and gene set enrichment analysis revealed specific dysregulated biological processes as well. Furthermore, proteins with altered expression unique to a specific lung cancer type were identified and could be the targets of future studies. Full article
(This article belongs to the Special Issue Clinical Proteomics in Proliferative Disorders)
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13 pages, 1426 KiB  
Article
Real World Evaluation of the Prosigna/PAM50 Test in a Node-Negative Postmenopausal Swedish Population: A Multicenter Study
by Una Kjällquist, Balazs Acs, Sara Margolin, Emelie Karlsson, Luisa Edman Kessler, Scarlett Garcia Hernandez, Maria Ekholm, Christine Lundgren, Erik Olsson, Henrik Lindman, Theodoros Foukakis, Alexios Matikas and Johan Hartman
Cancers 2022, 14(11), 2615; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14112615 - 25 May 2022
Cited by 5 | Viewed by 2551
Abstract
Molecular signatures to guide decisions for adjuvant chemotherapy are recommended in early ER-positive, HER2-negative breast cancer. The objective of this study was to assess what impact gene-expression-based risk testing has had following its recommendation by Swedish national guidelines. Postmenopausal women with ER-positive, HER2-negative [...] Read more.
Molecular signatures to guide decisions for adjuvant chemotherapy are recommended in early ER-positive, HER2-negative breast cancer. The objective of this study was to assess what impact gene-expression-based risk testing has had following its recommendation by Swedish national guidelines. Postmenopausal women with ER-positive, HER2-negative and node negative breast cancer at intermediate clinical risk and eligible for chemotherapy were identified retrospectively from five Swedish hospitals. Tumor characteristics, results from Prosigna® test and final treatment decision were available for all patients. Treatment recommendations were compared with the last version of regional guidelines before the introduction of routine risk signature testing. Among the 360 included patients, 41% (n = 148) had a change in decision for adjuvant treatment based on Prosigna® test result. Out of the patients with clinical indication for adjuvant chemotherapy, 52% (n = 118) could avoid treatment based on results from Prosigna® test. On the contrary, 23% (n = 30) of the patients with no indication were escalated to receive adjuvant chemotherapy after testing. Ki67 could not distinguish between the Prosigna® risk groups or intrinsic subtypes and did not significantly differ between patients in which decision for adjuvant therapy was changed based on the test results. In conclusion, we report the first real-world data from implementation of gene-expression-based risk assessment in a Swedish context, which may facilitate the optimization of future versions of the national guidelines. Full article
(This article belongs to the Special Issue Clinical Proteomics in Proliferative Disorders)
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17 pages, 2339 KiB  
Article
Mitochondrial ROS Produced in Human Colon Carcinoma Associated with Cell Survival via Autophagy
by Eun Ji Gwak, Dasol Kim, Hui-Yun Hwang and Ho Jeong Kwon
Cancers 2022, 14(8), 1883; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14081883 - 08 Apr 2022
Cited by 3 | Viewed by 2295
Abstract
Human colon carcinomas, including HCT116 cells, often exhibit high autophagic flux under nutrient deprivation or hypoxic conditions. Mitochondrial ROS (mROS) is known as a ‘molecular switch’ for regulating the autophagic pathway, which is critical for directing cancer cell survival or death. In early [...] Read more.
Human colon carcinomas, including HCT116 cells, often exhibit high autophagic flux under nutrient deprivation or hypoxic conditions. Mitochondrial ROS (mROS) is known as a ‘molecular switch’ for regulating the autophagic pathway, which is critical for directing cancer cell survival or death. In early tumorigenesis, autophagy plays important roles in maintaining cellular homeostasis and contributes to tumor growth. However, the relationships between mROS and the autophagic capacities of HCT116 cells are poorly understood. Ubiquinol cytochrome c reductase binding protein (UQCRB) has been reported as a biomarker of colorectal cancer, but its role in tumor growth has not been clarified. Here, we showed that UQCRB is overexpressed in HCT116 cells compared to CCD18co cells, a normal colon fibroblast cell line. Pharmacological inhibition of UQCRB reduced mROS levels, autophagic flux, and the growth of HCT116 tumors in a xenograft mouse model. We further investigated mutant UQCRB-overexpressing cell lines to identify functional links in UQCRB-mROS-autophagy. Notably, an increasing level of mROS caused by UQCRB overexpression released Ca2+ by the activation of lysosomal transient receptor potential mucolipin 1 (TRPML1) channels. This activation induced transcription factor EB (TFEB) nuclear translocation and lysosome biogenesis, leading to autophagy flux. Collectively, our study showed that increasing levels of mROS caused by the overexpression of UQCRB in human colon carcinoma HCT116 cells could be linked to autophagy for cell survival. Full article
(This article belongs to the Special Issue Clinical Proteomics in Proliferative Disorders)
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22 pages, 4439 KiB  
Article
Deciphering Biomarkers for Leptomeningeal Metastasis in Malignant Hemopathies (Lymphoma/Leukemia) Patients by Comprehensive Multipronged Proteomics Characterization of Cerebrospinal Fluid
by Pablo Juanes-Velasco, Norma Galicia, Elisa Pin, Ricardo Jara-Acevedo, Javier Carabias-Sánchez, Rodrigo García-Valiente, Quentin Lecrevisse, Carlos Eduardo Pedreira, Rafael Gongora, Jose Manuel Sanchez-Santos, Héctor Lorenzo-Gil, Alicia Landeira-Viñuela, Halin Bareke, Alberto Orfao, Peter Nilsson and Manuel Fuentes
Cancers 2022, 14(2), 449; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14020449 - 17 Jan 2022
Cited by 3 | Viewed by 2946
Abstract
In the present work, leptomeningeal disease, a very destructive form of systemic cancer, was characterized from several proteomics points of view. This pathology involves the invasion of the leptomeninges by malignant tumor cells. The tumor spreads to the central nervous system through the [...] Read more.
In the present work, leptomeningeal disease, a very destructive form of systemic cancer, was characterized from several proteomics points of view. This pathology involves the invasion of the leptomeninges by malignant tumor cells. The tumor spreads to the central nervous system through the cerebrospinal fluid (CSF) and has a very grim prognosis; the average life expectancy of patients who suffer it does not exceed 3 months. The early diagnosis of leptomeningeal disease is a challenge because, in most of the cases, it is an asymptomatic pathology. When the symptoms are clear, the disease is already in the very advanced stages and life expectancy is low. Consequently, there is a pressing need to determine useful CSF proteins to help in the diagnosis and/or prognosis of this disease. For this purpose, a systematic and exhaustive proteomics characterization of CSF by multipronged proteomics approaches was performed to determine different protein profiles as potential biomarkers. Proteins such as PTPRC, SERPINC1, sCD44, sCD14, ANPEP, SPP1, FCGR1A, C9, sCD19, and sCD34, among others, and their functional analysis, reveals that most of them are linked to the pathology and are not detected on normal CSF. Finally, a panel of biomarkers was verified by a prediction model for leptomeningeal disease, showing new insights into the research for potential biomarkers that are easy to translate into the clinic for the diagnosis of this devastating disease. Full article
(This article belongs to the Special Issue Clinical Proteomics in Proliferative Disorders)
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