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Biomarkers: Diagnostic Indicators for Human Ailments
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Biomarkers: Diagnostic Indicators for Human Ailments

A special issue of Diagnostics (ISSN 2075-4418). This special issue belongs to the section "Pathology and Molecular Diagnostics".

Deadline for manuscript submissions: closed (31 October 2024) | Viewed by 8327

Special Issue Editor

Dr. Jun Zhang

E-Mail Website
Guest Editor
Texas Tech University Health Sciences Center El Paso, El Paso, TX 79409 801, USA
Interests: angiogenesis; tumorigenesis; molecular genetics; molecular biology; biochemistry
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Biomarkers, indicators of medical conditions, play a pivotal role in both research and clinical settings. These quantifiable measures, observed externally, offer accurate and reproducible insights into a patient's health state. Their significance spans basic and clinical research, as well as routine clinical practice, and they have become integral even as primary endpoints in clinical trials.

The integration of biomarkers into clinical trials has become so commonplace that their inclusion as primary endpoints is widely accepted. This is particularly valid for well-defined biomarkers that consistently and accurately predict pertinent clinical outcomes across various treatments and populations. Such integration is not only justified but also essential for advancing medical knowledge and improving patient care.

By assembling comprehensive insights and discussions, this Special Issue strives to offer a holistic view of the diverse applications and implications of biomarkers across a spectrum of medical domains. The overarching goal is to enhance understanding among researchers, clinicians, and the medical community at large, thereby fostering the development of innovative diagnostic tools, effective treatment strategies, and improved patient outcomes. Through a multidimensional exploration of current biomarker research, this issue seeks to illuminate the path forward for harnessing the power of biomarkers in shaping the future of medicine.

Dr. Jun Zhang
Guest Editor

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. Diagnostics 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 2600 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
  • diagnostics
  • prognostic
  • predictive
  • patient care

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Published Papers (6 papers)

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Research

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11 pages, 1173 KiB  
Article
Kappa Free Light Chains in Multiple Sclerosis as a Marker of Intrathecal Humoral Response: A Sex-Disaggregated Study
by Raffaella Candeloro, Maila Galloppa, Laura Lombardo, Michele Laudisi, Sara Ghisellini, Giovanna Negri, Caterina Ferri, Carla Marcialis, Tiziana Bellini, Maura Pugliatti and Massimiliano Castellazzi
Diagnostics 2024, 14(24), 2798; https://doi.org/10.3390/diagnostics14242798 - 12 Dec 2024
Cited by 1 | Viewed by 1112
Abstract
Background: Kappa free light chains (KFLCs) are emerging as promising biomarkers for intrathecal B cell activity for diagnosing multiple sclerosis (MS) through cerebrospinal fluid (CSF) analysis. In this study, we evaluated the ability of KFLC formulas to identify the presence of MS and [...] Read more.
Background: Kappa free light chains (KFLCs) are emerging as promising biomarkers for intrathecal B cell activity for diagnosing multiple sclerosis (MS) through cerebrospinal fluid (CSF) analysis. In this study, we evaluated the ability of KFLC formulas to identify the presence of MS and their agreement with the ‘gold standard’ of CSF IgG oligoclonal bands (OCBs). Methods: A total of 233 patients were included in this study: 149, comprising 43 males and 106 females, had MS, and the remainder, 40 males and 44 females, had other neurological diseases (ONDs). We evaluated the potential of KFLCs in terms of sensitivity, specificity, and accordance. All analyses were conducted using a sex-disaggregated approach. Results: KFLCs showed a high sensitivity for both sexes with respect to the diagnosis of MS, with values between 74.42% and 93.03%. The specificity of the various formulas was much lower for females when compared to males, with values between 45.45% and 59.09%, with a significant difference between the two sexes for the K Index > 5.9 (p = 0.0451). Cohen’s kappa showed substantial agreement for men and moderate agreement for women between the KFLC indices and OCB. Conclusions: This study highlights the potential of KFLCs as a biomarker for MS but emphasises the need for sex-specific thresholds to improve diagnostic accuracy. Full article
(This article belongs to the Special Issue Biomarkers: Diagnostic Indicators for Human Ailments)
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10 pages, 244 KiB  
Article
Clinical and Biological Markers of Frailty Syndrome in Patients Undergoing Elective Percutaneous Coronary Intervention
by Kristina Krivoshapova, Daria Tsygankova, Anastasiya Neeshpapa, Anastasia Kareeva, Alexandr Kokov, Evgeny Bazdyrev, Victoria Karetnikova and Olga Barbarash
Diagnostics 2024, 14(23), 2663; https://doi.org/10.3390/diagnostics14232663 - 26 Nov 2024
Viewed by 754
Abstract
Background: The aim of this study was to analyze the prevalence of prefrailty and frailty syndrome (FS) in patients with coronary artery disease (CAD), and the clinical and biological characteristics of frail patients undergoing elective percutaneous coronary intervention (PCI). Material and Methods: The [...] Read more.
Background: The aim of this study was to analyze the prevalence of prefrailty and frailty syndrome (FS) in patients with coronary artery disease (CAD), and the clinical and biological characteristics of frail patients undergoing elective percutaneous coronary intervention (PCI). Material and Methods: The study included 78 patients with CAD who were admitted to the clinic to undergo PCI. To detect prefrailty and FS in patients, we used a short physical performance test battery (10–12 points—no FS, 8–9 points—prefrailty, 7 or fewer points—FS). We used the RayBio® Human ELISA Kit (Norcross, GA, USA), a highly sensitive and highly specific enzyme-linked immunosorbent assay, to determine the concentration of biological markers of inflammation (IL-6, IL-10, IL-13, IL-15, TNF-α) and bone, muscle, and fat remodeling (leptin, calcitonin, osteoprotegerin, osteocalcin, myostatin) in the serum of patients with coronary artery disease before planned PCI. Results: Taking into account the test battery score, the prevalence of FS in patients with CAD before elective PCI was 24.4%, the prevalence of prefrailty was 33.3%. According to the results of the study, older women with type 2 diabetes in their history were significantly more likely to be frail. Studying a wide range of biological markers of inflammation and musculoskeletal and fat remodeling, we noted lower levels of calcitonin (2.60 [1.50; 5.85] pg/mL, p = 0.018) and osteoprotegerin (0.80 [0.60; 1.20] ng/mL, p = 0.025) in the serum of frail patients with CAD. Later we confirmed the results by correlation analysis. Moreover, we found an association between FS and higher serum leptin levels in patients with CAD before elective PCI. Conclusion: The results of the study confirm the high prevalence of prefrailty (33.3%) and FS (24.4%) in patients with CAD. Older women with type 2 diabetes in their history were significantly more likely to be frail. At the same time, the presence of FS is associated with lower levels of calcitonin and osteoprotegerin, and higher levels of leptin in the serum of frail patients before elective PCI. Full article
(This article belongs to the Special Issue Biomarkers: Diagnostic Indicators for Human Ailments)
12 pages, 490 KiB  
Article
The Utility of Immuno-Nutritional Scores in Patients with Testicular Germ Cell Tumors
by Uros Bumbasirevic, Milos Petrovic, Vesna Coric, Nikola Lisicic, David Obucina, Milica Zekovic, Bogomir Milojevic, Nenad Vasilic, Vladimir Vasic, Marko Zivkovic, Nebojsa Bojanic and Aleksandar Janicic
Diagnostics 2024, 14(19), 2196; https://doi.org/10.3390/diagnostics14192196 - 1 Oct 2024
Cited by 1 | Viewed by 1001
Abstract
Background: Hemoglobin, Albumin, Lymphocyte, and Platelet Score (HALP) is an accessible score that is easily reproducible from routine laboratory testing while also reflecting patients’ immune-nutritional status. Along with other immuno-nutritional scores, such as the Prognostic Nutrition Index (PNI), HALP has been associated with [...] Read more.
Background: Hemoglobin, Albumin, Lymphocyte, and Platelet Score (HALP) is an accessible score that is easily reproducible from routine laboratory testing while also reflecting patients’ immune-nutritional status. Along with other immuno-nutritional scores, such as the Prognostic Nutrition Index (PNI), HALP has been associated with a number of clinical and pathological features. The goal of our study was to evaluate the prognostic utility of HALP and PNI scores in testicular germ cell cancer (GCT) patients. Methods: This case-only study included 203 testicular GCT patients who were classified according to the disease stage and HALP and PNI cut-offs. Complete blood count and albumin concentration were routinely determined. Results: The values of HALP and PNI significantly differed among different clinical stages (p < 0.05). Moreover, they clearly exposed a significantly higher risk of advanced clinical stage development for those testicular GCT patients with lower values of HALP and PNI (p < 0.05). Finally, lower score levels were associated with larger tumor size (p < 0.05). Conclusion: Our investigation could provide evidence that specific immune-nutritional scores can help distinguish individuals diagnosed with testicular GCT who are more likely to be identified with advanced disease stages. Full article
(This article belongs to the Special Issue Biomarkers: Diagnostic Indicators for Human Ailments)
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18 pages, 1296 KiB  
Article
The Pivotal Role of Presepsin in Assessing Sepsis-Induced Cholestasis
by Maria Iuliana Ghenu, Dorin Dragoș, Maria Mirabela Manea, Andra-Elena Balcangiu-Stroescu, Dorin Ionescu, Lucian Negreanu and Adelina Vlad
Diagnostics 2024, 14(16), 1706; https://doi.org/10.3390/diagnostics14161706 - 6 Aug 2024
Viewed by 1608
Abstract
Background: The serum levels of presepsin correlate with parameters indicating cholestasis in sepsis; however, the probability and significance of this association remain uncertain. We aimed to ascertain whether infection, as signaled by presepsin levels, is the primary determinant of elevated biliary parameters in [...] Read more.
Background: The serum levels of presepsin correlate with parameters indicating cholestasis in sepsis; however, the probability and significance of this association remain uncertain. We aimed to ascertain whether infection, as signaled by presepsin levels, is the primary determinant of elevated biliary parameters in sepsis. Methods: A unicenter, retrospective study included 396 COVID-free emergency-admitted patients, in which presepsin level was determined. Presepsin, neutrophil count, leukocyte count, C reactive protein, and fibrinogen evaluated the septic/inflammatory state. The statistically significant factors associated with cholestasis, ALT, and AST were analyzed by Fisher’s exact test and Spearman regression with Bonferroni’s correction. Results: Presepsin emerged as the most likely variable correlated with all cholestasis markers: alkaline phosphatase (p = 7 × 10−8), gamma-glutamyl transferase (p = 5 × 10−10), and conjugated bilirubin (p = 4 × 10−15). Thrombocyte count, C reactive protein, age, creatinine, urea, lactate, and blood pressure, were associated with only one or two of these markers. Conclusions: In a sepsis setting, the increase in cholestasis-related parameters is associated with presepsin with a higher probability than hemodynamic, inflammatory, or coagulation-related variables. Determining this robust link between sepsis and cholestasis could eliminate unnecessary imaging procedures in critically ill patients, enabling clinicians to focus efforts on addressing the primary infectious cause. Full article
(This article belongs to the Special Issue Biomarkers: Diagnostic Indicators for Human Ailments)
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Review

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19 pages, 491 KiB  
Review
Significance of Biogenetic Markers in Giant Cell Tumor Differentiation and Prognosis: A Narrative Review
by Muhammad Taqi, Haseeb ul Rasool, Mobeen Zaka Haider and Munjed Al Muderis
Diagnostics 2025, 15(1), 39; https://doi.org/10.3390/diagnostics15010039 - 27 Dec 2024
Viewed by 1536
Abstract
Background: Giant cell tumor of bone (GCTB) is a locally aggressive tumor. It accounts for only 5% of all bony tumors. Early diagnosis, and follow-up for recurrence is often difficult due to a lack of biogenetic markers. Giant cells are multinucleated epithelioid [...] Read more.
Background: Giant cell tumor of bone (GCTB) is a locally aggressive tumor. It accounts for only 5% of all bony tumors. Early diagnosis, and follow-up for recurrence is often difficult due to a lack of biogenetic markers. Giant cells are multinucleated epithelioid cells derived from macrophages. Histologically, giant cells are also present in other pathologies of bone, e.g., aneurysmal bone cyst, chondroblastoma, giant cell granuloma, and malignant giant cell tumor, etc. Similarly, radiographic findings overlap with other osteolytic lesions, making the diagnosis and prognosis of giant cell tumor very challenging. Aims and Objectives: The purpose of this study was to explore biological and genetic markers which can be used for detection, differentiation, recurrence, and prognosis of GCTB. This will help to better understand the clinical outcome of GCTB and minimize the need for interventions. Methods: We conducted a literature search using Google, Google Scholar, PubMed, Wiley Library, Medline, Clinical trials.org, and Web of Science. Our search strategy included MeSH terms and key words for giant cell tumor and biogenetic markers from date of inception to September 2020. After excluding review articles, 246 duplicates, and non-relevant articles, we included 24 articles out of 1568 articles, summarizing the role of biogenetic markers in the prognosis of GCT. Results: P63 is 98.6% sensitive and relatively specific for GCT as compared to other multinucleated giant cells containing neoplasms. MDM2 (mouse double minute 2 homolog), IGF1 (insulin-like growth factor 1), STAT1 (signal transducer and activator of transcription 1), and RAC1 (Ras-related C3 botulinum toxin substrate 1) are associated with GCTB recurrence, and might serve as biomarkers for it. Increased expression of the proteins STAT5B, GRB2, and OXSR1 was related to a higher probability of metastasis. H3F3A and H3F3B mutation analysis appears to be a highly specific, although less sensitive, diagnostic tool for the distinction of giant cell tumor of bone (GCTB) and chondroblastoma from other giant cell-containing tumors. A neutrophil to lymphocyte ratio (NLR) > 2.70, platelet to lymphocyte ratio (PLR) > 215.80, lymphocyte to monocyte ratio (LMR) ≤ 2.80, and albumin to globulin ratio (AGR) < 1.50 were significantly associated with decreased disease-free survival (DFS) (p < 0.05). Large amounts of osteoclast-related mRNA (cathepsin K, tartrate-resistant acid phosphatase, and matrix metalloproteinase9) in GCTs (p < 0.05) are associated with the grade of bone resorption. We propose that subarticular primary malignant bone sarcomas with H3.3 mutations represent true malignant GCTB, even in the absence of a benign GCTB component. IMP3 and IGF2 might be potential biomarkers for GCT of the spine in regulating the angiogenesis of giant cell tumor of bone and predicting patients’ prognosis. Conclusions: This review study shows serological markers, genetic factors, cell membrane receptor markers, predictive markers for malignancy, and prognostic protein markers which are highly sensitive for GCT and relatively specific for giant cell tumor. MDM2, IGF1, STAT1, RAC1 are important makers in determining recurrence, while P63 and H3F3A differentiate GCT from other giant cell-containing tumors. STAT5B, GRB2, and OXSR1 are significant in determining the prognosis of GCT. Apart from using radiological and histological parameters, we can add them to tumor work-up for definitive diagnosis and prognosis. Full article
(This article belongs to the Special Issue Biomarkers: Diagnostic Indicators for Human Ailments)
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37 pages, 2280 KiB  
Review
Endocrine Petrified Ear: Associated Endocrine Conditions in Auricular Calcification/Ossification (A Sample-Focused Analysis)
by Ana Valea, Claudiu Nistor, Mihai-Lucian Ciobica, Oana-Claudia Sima and Mara Carsote
Diagnostics 2024, 14(12), 1303; https://doi.org/10.3390/diagnostics14121303 - 19 Jun 2024
Viewed by 1665
Abstract
Petrified ear (PE), an exceptional entity, stands for the calcification ± ossification of auricular cartilage (CAC/OAC); its pathogenic traits are still an open matter. Endocrine panel represents one of the most important; yet, no standard protocol of assessments is available. Our objective was [...] Read more.
Petrified ear (PE), an exceptional entity, stands for the calcification ± ossification of auricular cartilage (CAC/OAC); its pathogenic traits are still an open matter. Endocrine panel represents one of the most important; yet, no standard protocol of assessments is available. Our objective was to highlight most recent PE data and associated endocrine (versus non-endocrine) ailments in terms of presentation, imagery tools, hormonal assessments, biopsy, outcome, pathogenic features. This was a comprehensive review via PubMed search (January 2000–March 2024). A total of 75 PE subjects included: 46 case reports/series (N = 49) and two imagery-based retrospective studies (N = 26) with CAC/OAC prevalence of 7–23% (N = 251) amid routine head/temporal bone CT scans. Endocrine PE (EPE): N = 23, male/female ratio = 10.5; average age = 56.78, ranges: 22–79; non-EPE cohort: N = 26; male/female ratio = 1.88, mean age = 49.44; ranges: 18–75 (+a single pediatric case).The longest post-diagnosis follow-up was of 6–7 years. The diagnosis of PE and endocrine anomalies was synchronous or not (time gap of 10–20 years). A novel case in point (calcified EPE amid autoimmune poly-endocrine syndrome type 2 with a 10-year post-diagnosis documented follow-up) was introduced. We re-analyzed EPE and re-classified another five subjects as such. Hence, the final EPE cohort (N = 50) showed: adrenal insufficiency was the most frequent endocrine condition (36%) followed by hypopituitarism (22%) and hypothyroidism (18%); 39% of the patients with adrenal failure had Addison’s disease; primary type represented 72% of all cases with hypothyroidism; an endocrine autoimmune (any type) component was diagnosed in 18%. We propose the term of “endocrine petrified ear” and a workflow algorithm to assess the potential hormonal/metabolic background in PE. Full article
(This article belongs to the Special Issue Biomarkers: Diagnostic Indicators for Human Ailments)
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