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Biomolecules
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Molecular, Cellular, and Blood Biomarkers in Diagnosis, Prognosis, Monitoring, and...
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Molecular, Cellular, and Blood Biomarkers in Diagnosis, Prognosis, Monitoring, and Treatment

A special issue of Biomolecules (ISSN 2218-273X). This special issue belongs to the section "Molecular Biology".

Deadline for manuscript submissions: 31 July 2025 | Viewed by 8609

Special Issue Editors

Dr. Jordi Camps

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Guest Editor
Unitat de Recerca Biomèdica (Biomedical Research Unit), Hospital Universitari de Sant Joan, Institut d’Investigació Sanitària Pere Virgili, Universitat Rovira i Virgili, Reus, Spain
Interests: oxidative stress; inflammation; metabolism; non-communicable diseases; infectious diseases
Special Issues, Collections and Topics in MDPI journals
Dr. Isabel Fort Gallifa

E-Mail Website
Guest Editor
Universitat Rovira i Virgili, Clinical Laboratory, Catalan Institute of Health, Camp de Tarragona-Terres de l’Ebre, Tarragona, Spain
Interests: Oxidative stress
Dr. Xavier Gabaldó Barrios

E-Mail Website
Guest Editor
Universitat Rovira i Virgili, Reference Laboratory, Camp de Tarragona-Terres de l’Ebre, Hospital Universitari de Sant Joan, Reus, Spain
Interests: biomarkers; inflammation

Special Issue Information

Dear Colleagues,

Biomarkers are pivotal in modern medicine, serving as vital clues that unlock the mysteries of diseases. By detecting subtle molecular, cellular, or biochemical changes, biomarkers enable early diagnosis, personalized treatment strategies, and precise monitoring of therapeutic responses. They revolutionize patient care by enhancing accuracy, efficiency, and patient outcomes. Biomarkers also drive drug discovery, guiding the development of targeted therapies and facilitating clinical trials. In essence, biomarkers illuminate the path towards a future of healthcare where interventions are precisely tailored to individual needs, leading to improved quality of life and better health outcomes for all. Presently, biomarker research occupies the focal point where biology and medicine converge.

By contributing to this Special Issue, you will have the opportunity to share your findings on the latest developments in molecular, cellular, and blood biomarkers. This platform also offers a unique opportunity for collaboration and networking with fellow researchers in this field. Whether you are exploring cancer signatures, unraveling neurodegenerative disease pathways, or investigating the biomarkers of any other non-communicable or infectious disease, your work has the potential to impact patient care. Moreover, your contributions will help advance diagnostic tools, prognostic models, monitoring techniques, and targeted therapies.

We encourage scientists like you to send original research articles and reviews that will cover any aspect of the effects of molecular, cellular, and blood biomarkers in diagnosis, prognosis, monitoring, and treatment. Your unique perspectives and insights are invaluable in our collective effort to translate research into tangible benefits for patients. Together, we can make a significant difference in patient care.

Dr. Jordi Camps
Dr. Isabel Fort Gallifa
Dr. Xavier Gabaldó Barrios
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. Biomolecules is an international peer-reviewed open access monthly 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 2700 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

  • biomarkers
  • infectious diseases
  • laboratory medicine
  • non-communicable diseases

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Published Papers (6 papers)

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Research

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14 pages, 2274 KiB  
Article
Tumor-Infiltrating Immune Cells and HLA Expression as Potential Biomarkers Predicting Response to PD-1 Inhibitor Therapy in Stage IV Melanoma Patients
by Barbara Hegyi, Kristóf György Csikó, Tímea Balatoni, Georgina Fröhlich, Katalin Bőcs, Erika Tóth, Anita Mohos, Anna Rebeka Neumark, Csenge Dorottya Menyhárt, Soldano Ferrone and Andrea Ladányi
Biomolecules 2024, 14(12), 1609; https://doi.org/10.3390/biom14121609 - 16 Dec 2024
Viewed by 926
Abstract
PD-1 inhibitors are known to be effective in melanoma; however, a considerable proportion of patients fail to respond to therapy, necessitating the identification of predictive markers. We examined the predictive value of tumor cell HLA class I and II expression and immune cell [...] Read more.
PD-1 inhibitors are known to be effective in melanoma; however, a considerable proportion of patients fail to respond to therapy, necessitating the identification of predictive markers. We examined the predictive value of tumor cell HLA class I and II expression and immune cell infiltration in melanoma patients treated with PD-1 inhibitors. Pretreatment surgical samples from 40 stage IV melanoma patients were studied immunohistochemically for melanoma cell expression of HLA class I molecules (using four antibody clones with different specificities), HLA-II, and immune cell infiltration (using a panel of 10 markers). Among the responders, the ratio of patients showing melanoma cell HLA-II expression was higher compared to non-responders (p = 0.0158), and similar results were obtained in the case of two anti-HLA-I antibodies. A combined score of HLA-I/II expression also predicted treatment response (p = 0.0019). Intratumoral infiltration was stronger in the responders for most immune cell types. Progression-free survival showed an association with HLA-II expression, the combined HLA score, and the density of immune cells expressing CD134 and PD-1, while overall survival was significantly associated only with HLA class II expression. Our findings corroborate previous results indicating the importance of immune cell infiltration and tumor cell HLA-II expression in the efficacy of PD-1 inhibitor treatment in a “real world” patient cohort and suggest the potential predictive role of HLA class I expression. Full article
(This article belongs to the Special Issue Molecular, Cellular, and Blood Biomarkers in Diagnosis, Prognosis, Monitoring, and Treatment)
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21 pages, 1861 KiB  
Article
Rapid Detection of PML::RARA Fusions in Acute Promyelocytic Leukemia: CRISPR/Cas9 Nanopore Sequencing with Adaptive Sampling
by William Middlezong, Victoria Stinnett, Michael Phan, Brian Phan, Laura Morsberger, Melanie Klausner, Jen Ghabrial, Natalie DeMetrick, Jing Zhu, Trisha James, Aparna Pallavajjala, Christopher D. Gocke, Maria R. Baer and Ying S. Zou
Biomolecules 2024, 14(12), 1595; https://doi.org/10.3390/biom14121595 - 13 Dec 2024
Viewed by 2075
Abstract
Acute promyelocytic leukemia (APL) accounts for approximately 10–15% of newly diagnosed acute myeloid leukemia cases and presents with coagulopathy and bleeding. Prompt diagnosis and treatment are required to minimize early mortality in APL as initiation of all-trans retinoic acid therapy rapidly reverses coagulopathy. [...] Read more.
Acute promyelocytic leukemia (APL) accounts for approximately 10–15% of newly diagnosed acute myeloid leukemia cases and presents with coagulopathy and bleeding. Prompt diagnosis and treatment are required to minimize early mortality in APL as initiation of all-trans retinoic acid therapy rapidly reverses coagulopathy. The PML::RARA fusion is a hallmark of APL and its rapid identification is essential for rapid initiation of specific treatment to prevent early deaths from coagulopathy and bleeding and optimize patient outcomes. Given limitations and long turnaround time of current gene fusion diagnostic strategies, we have developed a novel amplification-free nanopore sequencing-based approach with low cost, easy setup, and fast turnaround time. We termed the approach CRISPR/Cas9-enriched nanopore sequencing with adaptive sampling (CENAS). Using CENAS, we successfully sequenced breakpoints of typical and atypical PML::RARA fusions in APL patients. Compared with the standard-of-care genetic diagnostic tests, CENAS achieved good concordance in detecting PML::RARA fusions in this study. CENAS allowed for the identification of sequence information of fusion breakpoints involved in typical and atypical PML::RARA fusions and identified additional genes (ANKFN1 and JOSD1) and genomic regions (13q14.13) involving the atypical fusions. To the best of our knowledge, involvements of the ANKFN1 gene, the JOSD1 gene, and the 13q14.13 genomic region flanking with the SIAH3 and ZC3H13 genes have not been reported in the atypical PML::RARA fusions. CENAS has great potential to develop as a point-of-care test enabling immediate, low-cost bedside diagnosis of APL patients with a PML::RARA fusion. Given the early death rate in APL patients still reaches 15%, and ~10% of APL patients are resistant to initial therapy or prone to relapse, further sequencing studies of typical and atypical PML::RARA fusion might shed light on the pathophysiology of the disease and its responsiveness to treatment. Understanding the involvement of additional genes and positional effects related to the PML and RARA genes could shed light on their role in APL and may aid in the development of novel targeted therapies. Full article
(This article belongs to the Special Issue Molecular, Cellular, and Blood Biomarkers in Diagnosis, Prognosis, Monitoring, and Treatment)
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13 pages, 790 KiB  
Article
IL-4, IL-7, IL-9, NT, NRP1 May Be Useful Markers in the Diagnosis of Endometrial Cancer
by Mateusz Kozłowski, Dominika Borzyszkowska, Natalia Lerch, Agnieszka Turoń-Skrzypińska, Marta Tkacz, Jerzy Lubikowski, Maciej Tarnowski, Iwona Rotter and Aneta Cymbaluk-Płoska
Biomolecules 2024, 14(9), 1095; https://doi.org/10.3390/biom14091095 - 1 Sep 2024
Viewed by 1266
Abstract
The search for novel endometrial cancer diagnostic biomarkers is pertinent. The purpose of this study was to determine if IL-4, IL-7, IL-9, IL-10, NT, TSP-2, and NRP1 could be used as novel, helpful markers for the detection of endometrial cancer. Ninety-three women diagnosed [...] Read more.
The search for novel endometrial cancer diagnostic biomarkers is pertinent. The purpose of this study was to determine if IL-4, IL-7, IL-9, IL-10, NT, TSP-2, and NRP1 could be used as novel, helpful markers for the detection of endometrial cancer. Ninety-three women diagnosed with endometrial cancer (EC) and sixty-six patients with noncancerous endometrial lesions (NCEL) were included in this study. ELISA was used to measure the concentrations of the proteins tested. Median serum levels of IL-4, IL-7, IL-9, NT, and NRP1 were significantly higher in the EC group compared with NCEL. The cut-off level of IL-4 was set at 802.26 pg/mL with a sensitivity of 83.87% and a specificity of 50% (AUC = 0.7, p = 0.000023). The cut-off level of IL-7 was set at 133.63 ng/L with a sensitivity of 96.77% and a specificity of 75.76% (AUC = 0.91, p < 0.000001). The cut-off level of IL-9 was set at 228.79 pg/mL with a sensitivity of 69.89% and a specificity of 81.82% (AUC = 0.8, p < 0.000001). The cut-off level of NT was set at 275.43 pmol/L with a sensitivity of 94.62% and a specificity of 59.09% (AUC = 0.83, p < 0.000001). The cut-off level of NRP1 was set at 30.37 ng/mL with a sensitivity of 81.72% and a specificity of 57.58% (AUC = 0.71, p = 0.000004). This study suggests the clinical utility of IL-4, IL-7, IL-9, NT, and NRP1 in the diagnosis of endometrial cancer. Nevertheless, these biomarkers may also have prognostic or predictive value, which should be tested in future studies. Full article
(This article belongs to the Special Issue Molecular, Cellular, and Blood Biomarkers in Diagnosis, Prognosis, Monitoring, and Treatment)
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15 pages, 3537 KiB  
Article
Combining Metabolomics and Machine Learning to Identify Diagnostic and Prognostic Biomarkers in Patients with Non-Small Cell Lung Cancer Pre- and Post-Radiation Therapy
by Mauricio Murcia-Mejía, Marta Canela-Capdevila, Raquel García-Pablo, Andrea Jiménez-Franco, Juan Manuel Jiménez-Aguilar, Joan Badía, Rocío Benavides-Villarreal, Johana C. Acosta, Mónica Arguís, Alina-Iuliana Onoiu, Helena Castañé, Jordi Camps, Meritxell Arenas and Jorge Joven
Biomolecules 2024, 14(8), 898; https://doi.org/10.3390/biom14080898 - 24 Jul 2024
Cited by 2 | Viewed by 2415
Abstract
Lung cancer is the leading cause of cancer-related deaths globally, with non-small cell lung cancer (NSCLC) accounting for over 85% of cases and poor prognosis in advanced stages. This study explored shifts in circulating metabolite levels in NSCLC patients versus healthy controls and [...] Read more.
Lung cancer is the leading cause of cancer-related deaths globally, with non-small cell lung cancer (NSCLC) accounting for over 85% of cases and poor prognosis in advanced stages. This study explored shifts in circulating metabolite levels in NSCLC patients versus healthy controls and examined the effects of conventionally fractionated radiation therapy (CFRT) and stereotactic body radiation therapy (SBRT). We enrolled 91 NSCLC patients (38 CFRT and 53 SBRT) and 40 healthy controls. Plasma metabolite levels were assessed using semi-targeted metabolomics, revealing 32 elevated and 18 reduced metabolites in patients. Key discriminatory metabolites included ethylmalonic acid, maltose, 3-phosphoglyceric acid, taurine, glutamic acid, glycocolic acid, and d-arabinose, with a combined Receiver Operating Characteristics curve indicating perfect discrimination between patients and controls. CFRT and SBRT affected different metabolites, but both changes suggested a partial normalization of energy and amino acid metabolism pathways. In conclusion, metabolomics identified distinct metabolic signatures in NSCLC patients with potential as diagnostic biomarkers. The differing metabolic responses to CFRT and SBRT reflect their unique therapeutic impacts, underscoring the utility of this technique in enhancing NSCLC diagnosis and treatment monitoring. Full article
(This article belongs to the Special Issue Molecular, Cellular, and Blood Biomarkers in Diagnosis, Prognosis, Monitoring, and Treatment)
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Review

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29 pages, 942 KiB  
Review
The Role of IL-6 in Ischemic Stroke
by Hanna Pawluk, Alina Woźniak, Agnieszka Tafelska-Kaczmarek, Agnieszka Kosinska, Mateusz Pawluk, Krzysztof Sergot, Renata Grochowalska and Renata Kołodziejska
Biomolecules 2025, 15(4), 470; https://doi.org/10.3390/biom15040470 - 23 Mar 2025
Viewed by 428
Abstract
The pathophysiology of a stroke is a complex process involving oxidative stress and inflammation. As a result of the actions of reactive oxygen species (ROS), not only does vascular damage occur, but the brain tissue is also damaged. It is a dynamic process, [...] Read more.
The pathophysiology of a stroke is a complex process involving oxidative stress and inflammation. As a result of the actions of reactive oxygen species (ROS), not only does vascular damage occur, but the brain tissue is also damaged. It is a dynamic process, induced by a cellular–molecular immune response, focused on the development of an immediate reaction. During ischemia, inflammatory mediators are released, among which IL-6 plays a particularly important role in the acute phase of a stroke. Recently, a lot of attention has been devoted to this pleiotropic pro-inflammatory cytokine, which enhances the migration of leukocytes and is controlled by chemokines and the expression of adhesion handlers. The impact of IL-6 on the severity of neurological treatment and on patient prognosis in AIS is of interest to many researchers. More and more data indicate that it may be a reliable prognostic factor in strokes. Full article
(This article belongs to the Special Issue Molecular, Cellular, and Blood Biomarkers in Diagnosis, Prognosis, Monitoring, and Treatment)
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17 pages, 769 KiB  
Review
The Role of Circulating Biomarkers in Patients with Coronary Microvascular Disease
by Rossella Quarta, Giovanni Martino, Letizia Rosa Romano, Giovanni Lopes, Francesco Fabio Greco, Carmen Anna Maria Spaccarotella, Ciro Indolfi, Antonio Curcio and Alberto Polimeni
Biomolecules 2025, 15(2), 177; https://doi.org/10.3390/biom15020177 - 25 Jan 2025
Viewed by 744
Abstract
Coronary microvascular disease (CMD) comprises a spectrum of conditions characterized by the functional and structural abnormalities of coronary microcirculation, affecting vessels typically smaller than 500 μm. Despite its clinical significance as a contributor to myocardial ischemia, CMD frequently remains underdiagnosed due to the [...] Read more.
Coronary microvascular disease (CMD) comprises a spectrum of conditions characterized by the functional and structural abnormalities of coronary microcirculation, affecting vessels typically smaller than 500 μm. Despite its clinical significance as a contributor to myocardial ischemia, CMD frequently remains underdiagnosed due to the limitations of current diagnostic approaches. Invasive testing, including coronary reactivity assessment, is considered the gold standard, but it is resource-intensive and not always accessible. Non-invasive methods, such as positron emission tomography (PET) and transthoracic Doppler echocardiography (TTDE), offer alternatives but are limited by varying accuracy and accessibility. Amid these diagnostic challenges, there is increasing interest in circulating biomarkers as adjuncts in CMD evaluation. Biomarkers associated with endothelial dysfunction, inflammation, and oxidative stress, detectable through routine blood tests, may assist in CMD diagnosis, risk stratification, and therapeutic monitoring. These biomarkers can offer insights into CMD pathogenesis and enable early, non-invasive screening to identify patients who may benefit from more invasive investigations. This narrative review examines studies assessing biomarkers in CMD patients with diagnoses confirmed through invasive techniques. Our objective is to focus on circulating biomarkers linked to the invasive evaluation of coronary microcirculation, aiming to advance the understanding of the underlying mechanisms of this prevalent condition and enhance diagnostic accuracy and the clinical management of affected patients. Full article
(This article belongs to the Special Issue Molecular, Cellular, and Blood Biomarkers in Diagnosis, Prognosis, Monitoring, and Treatment)
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