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

Deadline for manuscript submissions: 31 May 2025 | Viewed by 13590

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Prof. Dr. Yuli Huang

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Department of Cardiology, Shunde Hospital, Southern Medical University, Foshan 528300, China
Interests: cardiovascular disease; heart failure; diabetes; biomarkers; public health; prevention
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Prof. Dr. Yong Yuan

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Department of Cardiology, Zhongshan City People's Hospital, Sun Yat-sen University, Zhongshan, China
Interests: cardiovascular disease; heart failure; biomarkers; coronary artery disease
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Prof. Dr. Peisong Chen

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Department of Laboratory Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China
Interests: laboratory medicine; precision medicine; risk prediction; clinical biomarkers
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Special Issue Information

Dear Colleagues,

Biomarkers are measurement biological variables, which can be detected in organ tissues, blood, or other body fluids. They can be mainly divided into two main types: prognostic and predictive biomarkers. Prognostic biomarkers are associated with the clinical outcomes (e.g., disease progression and recurrence, death) of the interested diseases, 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 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 as both prognostic and predictive.

With the great advances in proteomics, metabolomics, functional genomics, and bioinformatics, more and more novel biomarkers are discovering. 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 biomarkers identification and utilization in healthcare. The welcomed topics include but are not limited to biomarkers in cardiovascular disease, diabetes, acute and chronic venous disease, and cancer.

Prof. Dr. Yuli Huang
Prof. Dr. Yong Yuan
Prof. Dr. Peisong Chen
Guest Editors

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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. 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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Clinical Prognostic and Predictive Biomarkers in Diagnostics (20 articles)

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20 pages, 1592 KiB

Open AccessArticle

Correlation Between Prognostic Nutritional Index, Glasgow Prognostic Score, and Different Obesity-Related Indices in People with Diabetes or Prediabetes

by Roxana-Viorela Ahrițculesei, Lidia Boldeanu, Ionela Mihaela Vladu, Diana Clenciu, Adina Mitrea, Radu Cristian Cîmpeanu, Maria-Lorena Mustață, Isabela Siloși, Mihail Virgil Boldeanu and Cristin Constantin Vere

Diagnostics 2024, 14(23), 2661; https://doi.org/10.3390/diagnostics14232661 - 26 Nov 2024

Cited by 3 | Viewed by 935

Abstract

Background/Objectives: The prognostic nutritional index (PNI) and Glasgow Prognostic Score (GPS) are associated with patients’ nutritional and immune statuses. One important factor in the pathophysiology of type 2 diabetes mellitus (T2DM) is inflammation. Being present in insulin-target tissues, chronic tissue inflammation has become recognized as a crucial aspect of obesity and type 2 diabetes. This study aimed to compare the PNI and GPS levels of the subjects with T2DM to those of prediabetes (preDM) individuals. Furthermore, the goal was to investigate how these inflammatory markers relate to different types of obesity and whether the combination of PNI, GPS, and obesity-related indices was associated with any particular prognostic variables. Methods: In this study, we enrolled one-hundred patients with newly diagnosed T2DM and one-hundred patients with preDM. Results: Four findings emerged from this observational study. As a first observation, 28% of patients with preDM and 15% of patients with T2DM had a normal weight, while up to 43% of patients with preDM and 60% of patients with T2DM were obese. The second important observation was that the PNI of the T2DM patients was significantly lower than the PNI of the patients with preDM (p < 0.0001). The PNI showed that patients with T2DM had a moderate-to-severe malnutrition status (median value of 38.00). Patients with preDM had a mild-to-moderate malnutrition status (median value of 61.00) at diagnosis. Third, observed in the current study, preDM patients with PNI < 61.00 and T2DM patients with a PNI < 38.00 were associated with significantly higher median values of the waist-to-height ratio (WHtR) (p = 0.041, and p = 0.034, respectively) and body mass index (BMI) (p = 0.016, and p = 0.041, respectively). Fourth, this study also revealed, in the T2DM group, a moderate and statistically significant negative correlation between PNI and weight (rho = −0.322, p = 0.035), waist circumference (WC) (rho = −0.308, p = 0.042), hip circumference (HC) (rho = −0.338, p = 0.039), WHtR (rho = −0.341, p = 0.022), body adiposity index (BAI) (rho = −0.312, p = 0.032), and fasting plasma glucose (FPG) (rho = −0.318, p = 0.029). Additionally, the PNI values expressed a weak negative correlation with BMI (rho = −0.279, p = 0.015), and glycated hemoglobin A1c (HbA1c) (rho = −0.245, p = 0.025). The PNI levels exhibited a single positive correlation, weak but statistically significant, with estimated glomerular filtration rate (eGFR-CKD-EPI) values (rho = 0.263, p = 0.018). Conclusions: The findings of this study regarding the correlations between PNI, GPS, and different obesity-related indices in people with diabetes or prediabetes suggest that these indices, which assess nutritional and inflammatory status, can be used as independent predictor factors associated with the four pillars of DM management (glucose, blood pressure, lipids, and weight control) recommended by the American Diabetes Association (ADA). Full article

(This article belongs to the Special Issue Clinical Prognostic and Predictive Biomarkers, 2nd Edition)

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15 pages, 793 KiB

Open AccessArticle

Pre-Conception Androgen Levels and Obstetric Outcomes in Polycystic Ovary Syndrome: A Single-Center Retrospective Study

by Mónika Orosz, Fanni Borics, Dávid Rátonyi, Beáta Vida, Szilvia Csehely, Attila Jakab, Luca Lukács, Rudolf Lampé and Tamás Deli

Diagnostics 2024, 14(19), 2241; https://doi.org/10.3390/diagnostics14192241 - 8 Oct 2024

Viewed by 1268

Abstract

Hyperandrogenism is a determining diagnostic factor for PCOS. If pregnancy is conceived, it is considered high-risk due to several potential complications, but the correlation between pre-pregnancy androgen levels and obstetric outcomes is poorly characterized. Objective: To determine if pre-pregnancy serum androgen concentrations and androgen indexes differed when certain obstetric and neonatal outcomes appeared in PCOS. Methods: A single-center, retrospective study was carried out. All patients were treated between 2012 and 2019. A total of 73 patients had all the endocrine and obstetric data available. Pre-pregnancy hormone levels (total testosterone-T, androstenedione-AD, DHEAS (dehydroepiandrosterone sulfate), SHBG (sex-hormone-binding globulin), and TSH (thyroid-stimulating hormone) were collected, and T/SHBG, AD/SHBG, DHEAS/SHBG, T/AD indexes were calculated and compared. Results: When miscarriage was present in the history, significantly elevated pre-pregnancy AD levels were observed. Higher pre-pregnancy AD level was noted in PCOS patients delivering female newborns as compared to males. Additionally, a higher T/AD ratio was associated with subsequent preterm delivery, but significance was lost after age adjustment. Maternal age at delivery had a significant negative correlation with pre-pregnancy DHEAS levels and DHEAS/SHBG ratio. Pre-pregnancy SHBG displayed a significant negative correlation, while pre-pregnancy androgen/SHBG ratios exhibited positive correlations with both birth weight and birth weight percentile. Conclusions: Based on our data, AD and the T/AD ratio emerge as distinctive factors in certain outcomes, implying a potential specific role of altered 17-β-HSD (17β-hydroxysteroid dehydrogenase) enzyme activity, possibly influencing offspring outcomes. The pre-pregnancy T/SHBG ratio exhibits a potentially stronger correlation with fetal growth potential compared to SHBG alone. DHEAS and maternal age at delivery are strongly correlated in PCOS patients. Full article

(This article belongs to the Special Issue Clinical Prognostic and Predictive Biomarkers, 2nd Edition)

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12 pages, 1101 KiB

Open AccessArticle

Diagnostic Yield of Trio Whole-Genome Sequencing in Children with Undiagnosed Developmental Delay or Congenital Anomaly: A Prospective Cohort Study

by Jaewon Kim, Jaewoong Lee, Myungshin Kim and Dae-Hyun Jang

Diagnostics 2024, 14(15), 1680; https://doi.org/10.3390/diagnostics14151680 - 2 Aug 2024

Cited by 1 | Viewed by 1407

Abstract

Developmental delays (DD) and congenital anomalies (CA) are prevalent yet often remain undiagnosed despite comprehensive genetic testing. This study aims to investigate the diagnostic yield of trio whole-genome sequencing (WGS) in children presenting with DD or CA who remained undiagnosed after previous genetic testing. A prospective cohort study was conducted on children with undiagnosed DD or CA at a single tertiary hospital. All participants suspected of genetic conditions had undergone chromosome analysis, chromosome microarray analysis (CMA), and clinical exome sequencing (CES); however, a subset remained undiagnosed. The WGS test was administered to both the affected children and their parents. A total of 52 children were included, and 10 (19.2%) had undergone a genetic diagnosis through WGS. Eight of these cases were associated with autosomal dominant and de novo variants. WGS led to successful diagnosis due to several factors, including small structural variants, genes not covered in the CES panel, the discovery of newly implicated genes, issues related to coverage depth, low variant allele frequency, challenges in variant interpretation, and differences in the interpretation of variants of unknown significance among clinicians. This study highlights the clinical value of trio WGS testing in undiagnosed children with DD or CA. Notably, an additional 19.2% of affected children were diagnosed through this method. Full article

(This article belongs to the Special Issue Clinical Prognostic and Predictive Biomarkers, 2nd Edition)

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14 pages, 1461 KiB

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Markers of Epithelial–Mesenchymal Transition and Mucinous Histology Are Significant Predictors of Disease Severity and Tumor Characteristics in Early-Onset Colorectal Cancer

by Aleksandra Djikic Rom, Sandra Dragicevic, Radmila Jankovic, Sanja Radojevic Skodric, Predrag Sabljak, Velimir Markovic, Jovana Rosic Stojkovic, Goran Barisic and Aleksandra Nikolic

Diagnostics 2024, 14(14), 1512; https://doi.org/10.3390/diagnostics14141512 - 13 Jul 2024

Cited by 2 | Viewed by 1590

Abstract

Approximately 20% of patients with colorectal cancer (CRC) are diagnosed with a mucinous subtype of this tumor, have a worse prognosis, and often show resistance to available therapies. Molecules from the mucin family are involved in the regulation of epithelial–mesenchymal transition (EMT), which significantly determines the cancer aggressiveness. This study aimed to examine the diagnostic and prognostic significance of mucinous histology and EMT markers in patients with early-onset CRC and their association with disease severity and tumor characteristics. This study included tumor tissue samples from 106 patients diagnosed with CRC before the age of 45, 53 with mucinous and 53 with non-mucinous tumors. The EMT status was determined by immunohistochemical analysis of E-cadherin and Vimentin in tissue sections. Mucinous tumors had significantly higher Mucin-1 (p < 0.001) and cytoplasmic E-cadherin (p = 0.043) scores; they were significantly less differentiated (p = 0.007), more advanced (p = 0.027), and predominately affected right the colon (p = 0.039) compared to non-mucinous tumors. Epithelial tumors were significantly better differentiated (p = 0.034) and with less prominent tumor budding (p < 0.001) than mesenchymal tumors. Mucin-1 and Vimentin were independent predictors of tumor differentiation (p = 0.006) and budding (p = 0.001), respectively. Mucinous histology and EMT markers are significant predictors of disease severity and tumor characteristics in early-onset colorectal cancer. Full article

(This article belongs to the Special Issue Clinical Prognostic and Predictive Biomarkers, 2nd Edition)

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16 pages, 3132 KiB

Open AccessArticle

Combining Molecular and Traditional Prognostic Factors: A Holistic Approach to Breast Cancer Prognostication

by Liviu Moraru, Melinda Ildiko Mitranovici, Raluca Moraru, Septimiu Voidazan, Mihai Munteanu, Rares Georgescu, Dan Costachescu and Sabin Gligore Turdean

Diagnostics 2024, 14(13), 1449; https://doi.org/10.3390/diagnostics14131449 - 7 Jul 2024

Cited by 1 | Viewed by 1539

Abstract

Breast cancer is a heterogeneous disease with various morphologies and molecular features, and it is the second leading cause of cancer death in women in developed countries. According to the literature, we currently lack both prognostic biomarkers and therapeutic targets. The most important prognostic factors are disease stage and Nottingham grade. We conducted a retrospective analysis involving 273 patients with BC who underwent neoadjuvant therapy before proceeding to curative surgical treatment between 1 January 2014 and 31 December 2023. Pathological procedures were conducted at the Department of Pathology, Emergency County Hospital of Targu Mureș, Romania. A statistical analysis was performed. Regarding the relationship between Nottingham grade and Ki67, grade I was associated with a Ki67 of less than 14. The relationship between tumor grade and luminal was similar (p = 0.0001): Grade I was associated with luminal A. Regarding TNM stage, it was statistically significantly correlated with TILs (p = 0.01) and RCB (p = 0.0001). Stages III and IV were associated with a high RCB and poor prognosis. Regarding the prognostic value, Nottingham grade 3 and TNM stages III and IV were correlated with low overall survival and disease-free survival, with poor prognosis, and, among the molecular variables, RCB played the most important prognostic role. Full article

(This article belongs to the Special Issue Clinical Prognostic and Predictive Biomarkers, 2nd Edition)

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12 pages, 1025 KiB

Open AccessArticle

Exploring PGE2 and LXA4 Levels in Migraine Patients: The Potential of LXA4-Based Therapies

by Idris Kocaturk, Sedat Gulten, Bunyamin Ece and Fatma Mutlu Kukul Guven

Diagnostics 2024, 14(6), 635; https://doi.org/10.3390/diagnostics14060635 - 17 Mar 2024

Cited by 1 | Viewed by 1631

Abstract

Neurogenic inflammation plays a significant role in the pathogenesis of migraines. This study aimed to investigate the serum levels of prostaglandin E2 (PGE2), lipoxin A4 (LXA4), and other inflammatory biomarkers (C-reactive protein, fibrinogen) in migraine patients. In total, 53 migraine patients and 53 healthy controls were evaluated. Blood serum samples were collected during both attack and interictal periods and compared with the control group. In both the attack and interictal periods, PGE2 and LXA4 values were significantly lower in migraine patients compared to the control group (p < 0.001). Additionally, PGE2 values during the attack period were significantly higher than those during the interictal period (p = 0.016). Patients experiencing migraine attacks lasting ≥ 12 h had significantly lower serum PGE2 and LXA4 levels compared to those with attacks lasting < 12 h (p = 0.028 and p = 0.009, respectively). In ROC analysis, cut-off values of 332.7 pg/mL for PGE2 and 27.2 ng/mL for LXA4 were determined with 70–80% sensitivity and specificity. In conclusion, PGE2 and LXA4 levels are significantly lower in migraine patients during both interictal and attack periods. Additionally, the levels of LXA4 and PGE2 decrease more with the prolongation of migraine attack duration. Our findings provide a basis for future treatment planning. Full article

(This article belongs to the Special Issue Clinical Prognostic and Predictive Biomarkers, 2nd Edition)

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22 pages, 2199 KiB

Open AccessArticle

Role of Clinical Risk Factors and B-Type Natriuretic Peptide in Assessing the Risk of Asymptomatic Cardiotoxicity in Breast Cancer Patients in Kazakhstan

by Zhenisgul Tlegenova, Saule Balmagambetova, Bekbolat Zholdin, Gulnara Kurmanalina, Iliada Talipova, Arip Koyshybaev, Gulmira Sultanbekova, Mira Baspayeva, Saule Madinova, Kulparshan Kubenova, Aiganym Amanova and Amin Tamadon

Diagnostics 2023, 13(23), 3557; https://doi.org/10.3390/diagnostics13233557 - 28 Nov 2023

Cited by 1 | Viewed by 1618

Abstract

The asymptomatic progression of chemotherapy-induced cardiotoxicity poses a significant risk to breast cancer patients. In the present single-center cohort study, a predictive model for evaluating the risk of cardiotoxicity during or by the end of chemotherapy was designed. The risk-prediction nomogram was delineated and assessed. In total, 34 patients out of 120 developed asymptomatic cardiotoxicity (28.3%). Of six explored biomarkers, only B-type natriuretic peptide showed a reliable pattern of incremental increase, revealing statistical significance between cardiotoxicity “+” and “−” groups by visit 4 or by the 9th month of monitoring (p 0.006). The following predictors were included in the model: age, hypertension, diabetes mellitus, baseline glomerular filtration rate, 6 min walk test measured at visit 4, BNP values at visit 4, left ventricular ejection fraction levels at visit 4, a total dose of radiotherapy received, and anthracycline cumulative doses. The model’s AUC was 0.72 (95% CI 0.59; 0.86), evidencing the satisfactory predictive ability of the model; sensitivity 100% (95% CI 90.36; 100.0) at a specificity of 66.67% (95% CI 50.33; 79.79); PPV 54.1% [95% CI 47.13; 60.91]; PVN 100% [95% CI 94.64; 100.00]. The calibration plot showed satisfactory agreement between predicted and actual chances (p = 0.98). The designed model can be applied in settings lacking speckle tracking echocardiography. Full article

(This article belongs to the Special Issue Clinical Prognostic and Predictive Biomarkers, 2nd Edition)

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11 pages, 1429 KiB

Open AccessArticle

Predicting Peri-Operative Outcomes in Patients Treated with Percutaneous Thermal Ablation for Small Renal Masses: The SuNS Nephrometry Score

by Gennaro Musi, Stefano Luzzago, Giovanni Mauri, Francesco Alessandro Mistretta, Gianluca Maria Varano, Chiara Vaccaro, Sonia Guzzo, Daniele Maiettini, Ettore Di Trapani, Paolo Della Vigna, Roberto Bianchi, Guido Bonomo, Matteo Ferro, Zhe Tian, Pierre I. Karakiewicz, Ottavio de Cobelli, Franco Orsi and Mattia Luca Piccinelli

Diagnostics 2023, 13(18), 2955; https://doi.org/10.3390/diagnostics13182955 - 15 Sep 2023

Cited by 2 | Viewed by 1506

Abstract

Our objective was to develop a new, simple, and ablation-specific nephrometry score to predict peri-operative outcomes and to compare its predictive accuracy to PADUA and RENAL scores. Overall, 418 patients were treated with percutaneous thermal ablation (microwave and radiofrequency) between 2008 and 2021. The outcome of interest was trifecta status (achieved vs. not achieved): incomplete ablation or Clavien–Dindo ≥ 3 complications or postoperative estimated glomerular filtration rate decrease ≥ 30%. First, we validated the discrimination ability of the PADUA and RENAL scoring systems. Second, we created and internally validated a novel scoring (SuNS) system, according to multivariable logistic regression models. The predictive accuracy of the model was tested in terms of discrimination and calibration. Overall, 89 (21%) patients did not achieve trifecta. PADUA and RENAL scores showed poor ability to predict trifecta status (c-indexes 0.60 [0.53–0.67] and 0.62 [0.55–0.69], respectively). We, therefore, developed the SuNS model (c-index: 0.74 [0.67–0.79]) based on: (1) contact surface area; (2) nearness to renal sinus or urinary collecting system; (3) tumour diameter. Three complexity classes were created: low (3–4 points; 11% of no trifecta) vs. moderate (5–6 points; 30% of no trifecta) vs. high (7–8 points; 65% of no trifecta) complexity. Limitations include the retrospective and single-institution nature of the study. In conclusion, we developed an immediate, simple, and reproducible ablation-specific nephrometry score (SuNS) that outperformed PADUA and RENAL nephrometry scores in predicting peri-operative outcomes. External validation is required before daily practice implementation. Full article

(This article belongs to the Special Issue Clinical Prognostic and Predictive Biomarkers, 2nd Edition)

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7 pages, 2737 KiB

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A Case of Dedifferentiated Liposarcoma That Contributes to Accompanying Vessels of Various Size

by Yosuke Yamada, Kai Mizoguchi, Eisuke Shiba, Honami Mishima, Shinya Otsuki, Masahito Hoki, Masahiro Hirata, Akio Sakamoto, Shuichi Matsuda, Alexander Marx, Masanori Hisaoka and Hironori Haga

Diagnostics 2024, 14(15), 1679; https://doi.org/10.3390/diagnostics14151679 - 2 Aug 2024

Viewed by 1259

Abstract

Dedifferentiated liposarcoma (DDLPS) is a non-lipogenic sarcoma, generally arising from well-differentiated liposarcoma (WDLPS), although it can develop de novo. DDLPS tumors rarely trans-differentiate into non-adipose mesenchymal tissues; however, the latter lack notable variety and mostly show striated muscle or osteogenic/chondrogenic differentiation. Here, we report a case of DDLPS that contained numerous atypical vessels. A man in his sixties presented with a large tumor in his right thigh, and the tumor was surgically resected. Microscopically, most of the tumor was WDLPS, but a minor portion showed DDLPS, consisting of high-grade spindle cells. Remarkably, the DDLPS contained vessels of various sizes with atypical cytoarchitecture, including vessels with seemingly muscular layers. Immunohistochemically, the atypical cells within the vascular wall expressed aSMA, consistent with smooth muscle cells or pericytes, whereas surrounding high-grade spindle cells only focally expressed it, and these aSMA-positive cells within the vessels exhibited MDM2 amplification by immuno-fluorescence in situ hybridization. Our results demonstrate that DDLPS can trans-differentiate into smooth muscle cells of various-sized accompanying vessels, which may support their survival and proliferation. Full article

(This article belongs to the Special Issue Clinical Prognostic and Predictive Biomarkers, 2nd Edition)

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