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Diagnostics
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Clinical Prognostic and Predictive Biomarkers, Third Edition
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Clinical Prognostic and Predictive Biomarkers, Third Edition

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

Deadline for manuscript submissions: 31 March 2026 | Viewed by 5429

Special Issue Editors

Prof. Dr. Yuli Huang

E-Mail Website
Guest Editor
Department of Cardiology, Shunde Hospital, Southern Medical University, Foshan 528300, China
Interests: cardiovascular disease; heart failure; diabetes; biomarkers; public health; prevention
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Peisong Chen

E-Mail Website
Guest Editor
Department of Laboratory Medicine, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080, China
Interests: laboratory medicine; precision medicine; risk prediction; clinical biomarkers
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Biomarkers are measures of biological variables, which can be detected in organ tissues, blood, or other body fluids. They can be divided mainly into two main types: prognostic and predictive biomarkers. Prognostic biomarkers are associated with the clinical outcomes (e.g., disease progression, recurrence, and death) of the disease of interest, and are used to identify those with more aggressive disease status. Predictive biomarkers are used to identify individuals with a higher likelihood of response to a particular treatment, which allows for better identification of those who are more likely to benefit from a given treatment. Generally, biomarkers can be either prognostic or predictive, while in some cases they could be used for both prognostic and predictive purposes.

With the significant advances made in proteomics, metabolomics, functional genomics, and bioinformatics, more and more novel biomarkers are being discovered. They play an important role in identifying high-risk individuals, diagnosing disease conditions, and predicting response to therapy and prognosis in multiple fields of clinical medicine, including cardiovascular disease, diabetes, and cancer. Furthermore, they allow us to better understand the mechanisms and molecular pathways of disease development and progression. This deeper knowledge of biomarkers offers the opportunity to develop novel precision and personalized therapies.

In this Special Issue, we aim to provide a platform for communication on the progress of biomarker identification and utilization in healthcare. Topics of interest include, but are not limited to, biomarkers in cardiovascular disease, diabetes, acute and chronic venous disease, and cancer.

Prof. Dr. Yuli Huang
Prof. Dr. Peisong Chen
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 250 words) can be sent to the Editorial Office for assessment.

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
  • prognostic
  • predictive
  • risk stratification
  • cardiovascular disease
  • diabetes
  • cancer
  • hypertension
  • heart failure

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Published Papers (6 papers)

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Research

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13 pages, 774 KB  
Article
Dynamic Thyroglobulin Ratio as a Biomarker to Identify Papillary Thyroid Cancer Patients Who Would Benefit from a Low-Iodine Diet
by Su Woong Yoo, Yong Min Na, Young Jae Ryu, Hee Kyung Kim, Hyun-Jung Choi and Seong-Young Kwon
Diagnostics 2026, 16(3), 456; https://doi.org/10.3390/diagnostics16030456 - 1 Feb 2026
Viewed by 43
Abstract
Objectives: This study aimed to assess whether low-iodine diet (LID) adherence is associated with therapeutic response in papillary thyroid carcinoma (PTC), specifically in relation to post-therapeutic thyroglobulin (Tg) release as a surrogate marker for the acute radiation-induced response following radioactive iodine (RAI) [...] Read more.
Objectives: This study aimed to assess whether low-iodine diet (LID) adherence is associated with therapeutic response in papillary thyroid carcinoma (PTC), specifically in relation to post-therapeutic thyroglobulin (Tg) release as a surrogate marker for the acute radiation-induced response following radioactive iodine (RAI) therapy. Methods: This retrospective study included 895 patients with PTC treated with RAI. LID adherence was assessed using the urine iodine-to-creatinine (I/Cr) ratio, with <66.2 μg/g Cr defined as good adherence. The Tg ratio (ratioTg), calculated by dividing post-RAI Tg (measured 7 days after RAI) by pre-RAI Tg, was used to reflect the magnitude of the radiation-induced Tg release. Patients were stratified by ratioTg (≤1 vs. >1), and associations between LID adherence and therapeutic response were analyzed within each group. Results: Well-adherent patients exhibited significantly higher ratioTg compared to poorly adherent patients (15.7 ± 2.2 vs. 8.9 ± 1.3, p = 0.007). Among patients with ratioTg > 1 (n = 630), LID adherence was independently associated with improved therapeutic response (OR, 2.004; 95% CI, 1.270–3.162; p = 0.003). No such association was observed in patients with ratioTg ≤ 1 (n = 265; p = 0.546). Conclusions: The clinical benefit of LID appears to depend on the presence of a certain magnitude of radiation-induced Tg release. RatioTg may serve as a useful marker for identifying patients likely to benefit from LID. Full article
(This article belongs to the Special Issue Clinical Prognostic and Predictive Biomarkers, Third Edition)
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12 pages, 359 KB  
Article
Analysis of Neutrophil/Lymphocyte Ratio as a Potential Biomarker Stratified by Breast Cancer Histologic Subtype
by Emily Hunt, Matthew Davis, Wei Hou, Henrietta Bains, Timothy Darby, Julia Hou, Julie Chung, Roham Hadidchi, Tim Q. Duong and Takouhie Maldjian
Diagnostics 2026, 16(3), 449; https://doi.org/10.3390/diagnostics16030449 - 1 Feb 2026
Viewed by 36
Abstract
Background/Objectives: Breast cancer is the most common cancer in women. The neutrophil/lymphocyte ratio (NLR) is an emerging biomarker from peripheral blood that has been associated with breast cancer prognosis in some studies; however, some studies fail to demonstrate an association. We stratified [...] Read more.
Background/Objectives: Breast cancer is the most common cancer in women. The neutrophil/lymphocyte ratio (NLR) is an emerging biomarker from peripheral blood that has been associated with breast cancer prognosis in some studies; however, some studies fail to demonstrate an association. We stratified breast cancer patients into invasive lobular carcinoma (ILC) and invasive ductal carcinoma (IDC) cohorts to evaluate if any meaningful association could be found in either cohort between NLR and mortality. Additionally, no prior studies have examined the relationship between NLR and background parenchymal enhancement (BPE) on breast MRI, an imaging feature linked to increased breast cancer risk and a potential imaging prognostic biomarker, so we examined the relationship between BPE and NLR in the two cohorts. Methods: This retrospective study included 794 breast cancer patients who had either IDC or ILC. Radiologists’ MRI reports and their BI-RADS categorization of BPE (1 = minimal, 2 = mild, 3 = moderate, 4 = marked) were extracted and recorded. The NLR was calculated from blood counts obtained prior to treatment. Tumor characteristics were also recorded. Results: For patients with ILC, NLR was found to be associated with mortality. Additionally, patients with ILC and a high BPE had a significantly higher mean NLR compared to all other groups, including low BPE groups and all IDC groups. Conclusions: There is potential value in using NLR, a readily available blood biomarker, in models predicting prognosis in ILC patients. Full article
(This article belongs to the Special Issue Clinical Prognostic and Predictive Biomarkers, Third Edition)
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13 pages, 4153 KB  
Article
JAK3 Staining and CD68+ Macrophage Counts Are Increased in Patients with IgA Nephropathy
by Mateus Justi Luvizotto, Precil Diego Miranda de Menezes Neves, Cristiane Bitencourt Dias, Lecticia Barbosa Jorge, Luis Yu, Luísa Menezes-Silva, Magaiver Andrade-Silva, Renato C. Monteiro, Niels Olsen Saraiva Câmara and Viktoria Woronik
Diagnostics 2026, 16(3), 437; https://doi.org/10.3390/diagnostics16030437 - 1 Feb 2026
Viewed by 54
Abstract
Background/Objectives: IgA nephropathy (IgAN) is the most common primary glomerulopathy worldwide; it is characterized by a complex pathophysiology involving several inflammatory pathways. The Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway may be critical in this process. This study aimed to [...] Read more.
Background/Objectives: IgA nephropathy (IgAN) is the most common primary glomerulopathy worldwide; it is characterized by a complex pathophysiology involving several inflammatory pathways. The Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway may be critical in this process. This study aimed to investigate the role of this pathway in IgAN and examine related tissue inflammatory markers. Methods: We analyzed 63 biopsy-confirmed patients with IgAN and performed immunohistochemical analysis on renal samples. A panel of antibodies targeting the JAK/STAT pathway, including JAK2, JAK3, p-STAT, STAT3, and MAPK/ERK, was used for this analysis. Six kidney tumor border samples were used as controls. Additionally, CD68 staining was used to evaluate tissue inflammation in the kidney biopsies. Results: Patients with IgAN showed a significantly higher cellular density of JAK3 staining at the glomerular level compared to controls, indicating JAK3 activation (p < 0.0002). Nevertheless, the correlation between JAK3 positivity in glomeruli and clinical parameters such as the initial and final estimated glomerular filtration rate (eGFR) and proteinuria was not statistically significant. Identical results were obtained with CD68+ macrophage counts in the glomerular compartment, which did not show any correlation with clinical parameters, while CD68+ tubulointerstitial staining demonstrated a significant correlation with both initial (p = 0.002) and final eGFRs (p = 0.0014), proteinuria (p = 0.010), and interstitial fibrosis (p < 0.001), as well as with renal disease progression (p = 0.005). Conclusions: Activation of the JAK/STAT pathway was observed in patients with IgAN relative to controls, notwithstanding the inability to assess the full pathway due to technical limitations. Macrophage CD68 staining in the tubulointerstitial area increased and was associated with clinical and laboratory parameters such as eGFR and proteinuria. Additionally, MEST-C histological parameters, such as segmental glomerulosclerosis (S0/S1), tubular atrophy/interstitial fibrosis (T0/T1/T2), and crescents (C0/C1/C2), were associated with a higher number of CD68+ cells. Full article
(This article belongs to the Special Issue Clinical Prognostic and Predictive Biomarkers, Third Edition)
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Review

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16 pages, 901 KB  
Review
Biomarkers in Rheumatoid Arthritis: From Traditional Serology to Precision Medicine Integration
by Muhammad Soyfoo and Julie Sarrand
Diagnostics 2026, 16(2), 330; https://doi.org/10.3390/diagnostics16020330 - 20 Jan 2026
Viewed by 313
Abstract
The biomarker landscape in rheumatoid arthritis (RA) is evolving from reliance on traditional markers toward integrated, multimodal strategies enabling precision medicine approaches. To critically evaluate emerging biomarkers across serological, cellular, genetic, imaging, and multi-omic domains, distinguishing those approaching clinical readiness from those requiring [...] Read more.
The biomarker landscape in rheumatoid arthritis (RA) is evolving from reliance on traditional markers toward integrated, multimodal strategies enabling precision medicine approaches. To critically evaluate emerging biomarkers across serological, cellular, genetic, imaging, and multi-omic domains, distinguishing those approaching clinical readiness from those requiring further development. In this study, a narrative review of the literature published between 2000 and 2024 relevant to clinical decision-making in RA was conducted. Among novel serological markers, 14-3-3η protein and anti-carbamylated protein antibodies show the strongest validation for seronegative disease and prognostic stratification. Calprotectin demonstrates utility for disease activity monitoring and de-escalation decisions. Multi-biomarker disease activity scores provide an objective assessment but lack outcome trial validation. Musculoskeletal ultrasound offers accessible imaging biomarker capability, while MRI bone marrow edema remains the strongest structural progression predictor. Synovial tissue pathotyping has demonstrated proof-of-concept for treatment stratification. Genetic, epigenetic, and metabolomic approaches remain investigational. Key clinical implications include using 14-3-3η and calprotectin to inform seronegative diagnosis and de-escalation decisions, integrating ultrasound for remission verification, and recognizing that emerging biomarkers for extra-articular complications, including cardiovascular risk and venous thromboembolism, represent important unmet needs. Full article
(This article belongs to the Special Issue Clinical Prognostic and Predictive Biomarkers, Third Edition)
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17 pages, 820 KB  
Review
Microtubule Minus-End Binding Proteins in Cancer: Advances
by Qingwen Wang, Xiuling Li, Meng Xie, Xiangming Ding and Dongxiao Li
Diagnostics 2025, 15(24), 3116; https://doi.org/10.3390/diagnostics15243116 - 8 Dec 2025
Viewed by 503
Abstract
Microtubule minus-end binding proteins (−TIPs) are critical regulators of microtubule dynamics and stability, whose dysfunctions are increasingly associated with tumorigenesis and cancer progression. This review systematically consolidates current research advances on the molecular characteristics, oncogenic mechanisms, and therapeutic potential of −TIPs in cancer. [...] Read more.
Microtubule minus-end binding proteins (−TIPs) are critical regulators of microtubule dynamics and stability, whose dysfunctions are increasingly associated with tumorigenesis and cancer progression. This review systematically consolidates current research advances on the molecular characteristics, oncogenic mechanisms, and therapeutic potential of −TIPs in cancer. By integrating preclinical studies, multi-omics data, and clinical evidence, it was found that calmodulin-regulated spectrin-associated proteins (CAMSAPs) and abnormal spindle microtubule assembly (ASPM) primarily exhibit oncogenic properties, whereas CAMSAP3 acts as a tumor suppressor by negatively regulating tumor cell migration. Studies also demonstrate that pharmacological inhibition of the γ-tubulin ring complex (γ-TuRC) effectively attenuates the centrosomal hyper-clustering capacity of malignant cells, thereby suppressing invasive phenotypes. This result underscores the therapeutic value of targeting −TIPs. In summary, −TIPs play critical and complex roles in cancer progression and hold significant potential as prognostic biomarkers and therapeutic targets. Intervention strategies focusing on specific −TIPs, such as γ-TuRC, offer promising strategies for precision cancer therapy; however, the context-dependent functions of these proteins require further investigation to facilitate clinical translation. Full article
(This article belongs to the Special Issue Clinical Prognostic and Predictive Biomarkers, Third Edition)
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30 pages, 1403 KB  
Review
Role of Interleukins in Type 1 and Type 2 Diabetes
by Roha Asif, Ammara Khalid, Tolga Mercantepe, Aleksandra Klisic, Sana Rafaqat, Saira Rafaqat and Filiz Mercantepe
Diagnostics 2025, 15(15), 1906; https://doi.org/10.3390/diagnostics15151906 - 30 Jul 2025
Cited by 5 | Viewed by 4033
Abstract
Background: Despite distinct etiologies, type 1 diabetes (T1D) and type 2 diabetes (T2D) share chronic inflammation as a core feature. Interleukins, key immune mediators, play important yet still not fully understood roles in the development and complications of both conditions. Objective: [...] Read more.
Background: Despite distinct etiologies, type 1 diabetes (T1D) and type 2 diabetes (T2D) share chronic inflammation as a core feature. Interleukins, key immune mediators, play important yet still not fully understood roles in the development and complications of both conditions. Objective: This narrative review aims to provide a comprehensive and critical synthesis of current evidence on the role of key interleukins in T1D and T2D, highlighting their immunological functions, genetic associations, clinical correlations, and translational potential. Methods: A targeted literature search was conducted in PubMed, Google Scholar, and ScienceDirect up to January 2025, focusing on English-language clinical and experimental studies involving interleukins and their relevance to T1D and T2D. Reference lists were manually screened for additional sources. Interleukins (ILs) were reviewed individually to assess their immunobiology, disease specificity, and biomarker or therapeutic value. Findings: Pro-inflammatory cytokines such as IL-1β, IL-6, and IL-17 contribute to islet inflammation, insulin resistance, and microvascular damage in both T1D and T2D. Anti-inflammatory mediators including IL-4, IL-10, and IL-13 exhibit protective effects but vary in expression across disease stages. Less-characterized interleukins such as IL-3, IL-5, IL-9, and IL-27 demonstrate dual or context-dependent roles, particularly in shaping immune tolerance and tissue-specific complications such as nephropathy and neuropathy. Polymorphisms in IL-10 and IL-6 genes further suggest genetic contributions to interleukin dysregulation and metabolic dysfunction. Despite promising insights, translational gaps persist due to overreliance on preclinical models and limited longitudinal clinical data. Conclusions: Interleukins represent a mechanistic bridge linking immune dysregulation to metabolic derangements in both T1D and T2D. While their diagnostic and therapeutic potential is increasingly recognized, future research must address current limitations through isoform-specific targeting, context-aware interventions, and validation in large-scale, human cohorts. A unified interleukin-based framework may ultimately advance personalized strategies for diabetes prevention and treatment. Full article
(This article belongs to the Special Issue Clinical Prognostic and Predictive Biomarkers, Third Edition)
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