Novel Biomarkers For Early Prediction Research Articles

DHEA-S, Androstenedione, 17-β-estradiol signature as novel biomarkers for early prediction of risk of malignant pleural mesothelioma linked to asbestos-exposure: A preliminary investigation

17-β-estradiol, involved in mesothelioma pathogenesis, and its precursors were explored as potential biomarkers for the early diagnosis of mesothelioma. Using enzyme-linked immunosorbent assay(ELISA) for 17-β-estradiol and ultra-high performance liquid chromatography/tandem mass spectrometry(UHPLC-MS/MS) for 19 17-β-estradiol precursors, a comprehensive analysis of 20steroid hormones was conducted in the serum of mesothelioma patients(n=67), asbestos-exposed healthy subjects(n=39), and non-asbestos-exposed healthy subjects(n=35). Bioinformatics analysis explored three potential serum biomarkers: 17-β-estradiol, DHEA-S, and androstenedione. The results revealed significant differences in 17-β-estradiol levels between mesothelioma patients and both non-asbestos-exposed and asbestos-exposed healthy subjects. No significant variations in serum 17-β-estradiol levels were observed among mesothelioma patients at different stages, suggesting its potential as an early diagnostic marker. 17-β-estradiol levels were similar in mesothelioma patients with environmental and occupational asbestos exposure, while males with occupational asbestos exposure exhibited significantly higher levels of 17-β-estradiol compared to females. Significant reduction in androstenedione and an increase in DHEA-S were observed in asbestos-exposed individuals compared to non-asbestos-exposed individuals. The analysis of DHEA-S-androstenedione-17-β-estradiol signature score showed an increase in asbestos-exposed individuals and mesothelioma patients compared to non-asbestos-exposed individuals, and this score effectively distinguished between the groups. The Cancer Genome Atlas data was utilized to analyze the expression of 5-α-reductase1 and hydroxysteroid-17β-dehydrogenase2 genes. The findings indicated that mesothelioma patients with elevated gene values for 5-α-reductase1 and hydroxysteroid-17β-dehydrogenase2 have a worse or better prognosis on overall survival, respectively. In conclusion, this study suggests 17-β-estradiol, DHEA-S, and androstenedione as biomarkers for mesothelioma risk and early diagnosis of mesothelioma in asbestos-exposed individuals, aiding timely intervention and improved care.

Serum phosphate levels and the development of sepsis associated acute kidney injury: evidence from two independent databases.

We aimed to investigate the association between serum phosphate levels and the risk for developing sepsis associated acute kidney injury (SAKI). Septic patients from the Medical Information Mart for Intensive Care IV (MIMIC IV) and the eICU Collaborative Research Database (eICU-CRD) were enrolled. Restricted cubic spline (RCS) was used to visualize the relationship between phosphate levels and the risk of SAKI. Patients were divided into four categories based on their serum phosphate levels. Logistic regression analysis, receiver operating characteristic (ROC) curve and subgroup analysis were performed to evaluate the predictive value of serum phosphate for SAKI. A total of 9,244 and 2,124 patients from the MIMIC IV and eICU-CRD database were included in the final analysis. RCS curve revealed a non-linear correlation between phosphate levels and the risk of SAKI (p for non-linearity <0.05). Each 1 mg/dL increase in phosphate levels was associated with a 1.51 to 1.64-fold increased risk of SAKI (OR 2.51-2.64, p < 0.001) in the MIMIC IV cohort and a 0.29 to 0.38-fold increased risk (OR 1.29-1.38, p < 0.001) in the eICU-CRD cohort. Compared to the normal-low category, hyperphosphatemia and normal-high category were independently associated with an increased risk of SAKI, while hypophosphatemia was independently associated with a decreased risk in the MIMIC IV cohort. A similar trend was observed in the eICU-CRD cohort, but statistical significance disappeared in the hypophosphatemia category and the adjusted model of normal high category. These finding was consistent in subgroup analysis. Elevated serum phosphate, even within the normal range, is an independent risk factor for developing SAKI in septic patients. Abnormal change in serum phosphate levels may be a novel biomarker for early prediction of SAKI occurrence.

Serum IL-12p40: A novel biomarker for early prediction of minimal change disease relapse following glucocorticoids therapy.

Minimal change disease (MCD) has a high recurrence rate, but currently, no biomarker can predict its recurrence. To this end, this study aimed at identifying potential serum cytokines as valuable biomarkers for predicting the risk of MCD recurrence. Raybiotech 440 cytokine antibody microarray was used to detect the serum samples of eight relapsed, eight non-relapsed MCD patients after glucocorticoid treatment, and eight healthy controls. The differentially expressed cytokines were confirmed by enzyme-linked immunosorbent assay (ELISA) with serum samples from 29 non-relapsed and 35 relapsed MCD patients. The study used the receiver operating characteristic (ROC) curve analysis to investigate the sensitivity and specificity of a serum biomarker for predicting the MCD relapse. Serum IL-12p40 levels increased significantly in the relapsed group. The Area Under the ROC Curve (AUC) of IL-12p40 was 0.727 (95%CI: 0.597-0.856; P < 0.01). The RNA-sequencing analysis and qPCR assay performed on the IL-12 treated mouse podocytes and the control group showed increased expression of podocyte damage genes, such as connective tissue growth factor (CTGF), matrix metallopeptidase 9 (MMP9), secreted phosphoprotein 1 (SPP1), and cyclooxygenase-2 (COX-2) in the former group. IL-12p40 may serve as a new biomarker for predicting the risk of MCD recurrence after glucocorticoid treatment, and it may be involved in the pathogenesis and recurrence of MCD.

M215 Usefulness of various albumin adjusted ischemia modified albumin as novel biomarker for early prediction of renal damage in diabetes

M215 Usefulness of various albumin adjusted ischemia modified albumin as novel biomarker for early prediction of renal damage in diabetes

Overexpression of miR-126 Protects Hypoxic-Reoxygenation-Exposed HUVEC Cellular Injury through Regulating LRP6 Expression.

The aim of the study was to explore the clinical impact of circulatory miR-126 as a candidate for novel biomarker in patients with coronary artery disease (CAD) and its protective role against hypoxia/reoxygenation- (H/R-) exposed HUVEC cellular injury. A total of 278 subjects, which included 153 subjects with angiographically confirmed CAD, 70 unstable angina subjects, and 55 healthy individuals, along with 18-hour HR-induced HUVECs were recruited in this study. Plasma miR-126 levels were significantly downregulated in stable and unstable CAD patients as well as 18-hour HR-exposed HUVECs as compared with controls. Stable and unstable CAD subjects were significantly differentiated from healthy individuals with a predictive value of AUC 0.903 and 0.923, respectively. Moreover, peripheral circulatory miR-126 expressions in elderly (71-90 years) stable and unstable CAD patients were comparatively lower than younger (30-50 years) subjects. The caspase-3 activity, intracellular ROS concentrations, and cellular viabilities were evidently increased in 18-hour HR-exposed HUVECs than in normal cells (P < 0.001). On the contrary, mimic expressions of miR-126 prominently reduced caspase-3 activity and intracellular ROS levels and markedly enhanced HUVEC cellular viabilities (P < 0.001). LRP6 expressions were significantly elevated in HR-induced HUVECs, whereas overexpression of miR-126 remarkably decreased LRP6 expressions (P < 0.001). Plasma miR-126 could be used as a novel biomarker for early prediction of CAD subjects. Overexpression of miR-126 significantly improved HUVEC cellular viabilities by downregulation of LRP6 protein expression, suggesting a potential therapeutic target for CAD patients.

Multiple-Cytokine Profiling: A Novel Method for Early Prediction of the Efficacy of Sublingual Immunotherapy in Allergic Rhinitis Patients.

BackgroundAllergic rhinitis (AR) is a common inflammatory airway disease, and allergen-specific immunotherapy (AIT) is the only disease-modifying treatment for it. However, not all AR patients respond to AIT, and early prediction of patient response is extremely important. This study aimed to example serum levels of multiple cytokines in AR and explore their association with the efficacy of AIT.MethodsA total of 74 AR patients treated with sublingual immunotherapy (SLIT) were prospectively recruited. Serum samples were obtained before the onset of SLIT and cytokine levels detected by multiplex analysis. All patients were followed for >1 year, and associations between cytokine levels and the early efficacy of SLIT were evaluated. Significantly distinctive cytokines were further verified in another independent cohort.ResultsSixty patients completed the visit schedule set: 35 patients were put into a responder group and 25 a nonresponder group. Multiple-cytokine profiling showed that cytokine levels differed significantly between the two groups. The responder group had higher concentrations of BAFF and CCL11 and lower levels of CCL2, CCL7, IFNγ, IL8, IL10, IL16, and IL33 than the nonresponder group (P<0.05). Receiver-operating characteristic curves highlighted that serum BAFF, IFNγ, IL10, and IL33 levels were strongly predictive of the efficacy of SLIT (area under the curve <0.7, P<0.05). Serum IL10 and IL33 were overexpressed in nonresponders in the validation cohort. Patients in the responder group exhibited significantly higher IL10 levels and lower IL33 post-SLIT than pre-SLIT (P<0.05), but no statistical difference was found in nonresponders (P<0.05).ConclusionOur data indicated that serum multiple-cytokine profiling was associated with response to SLIT and that IL10 and IL33 might serve as novel biomarkers for early prediction of efficacy and be involved in the therapeutic mechanisms of SLIT in AR patients.

Red blood cell distribution width and tumor necrosis factor-α for the early prediction of coronary artery lesion in Kawasaki disease: a retrospective study.

We aimed to identify novel risk factors for the early prediction of coronary artery lesion (CAL) in children with Kawasaki disease (KD). We retrospectively analyzed data from hospitalized children newly diagnosed with KD between January 1, 2018, and December 31, 2020, with the following inclusion criteria: (1) diagnosis of KD, (2) first onset of CAL after admission, (3) with complete clinical records. Demographic and laboratory data were collected and analyzed. The independent risk factors of KD combined with CAL were identified by multivariate logistic regression analysis, followed by receiver operating characteristic (ROC) curve analysis to calculate the efficacy of identified risk factors in predicting KD combined with CAL. Among 241 initially recruited patients, 226 were eligible to be included in the study. Based on echocardiographic indications of CAL, 104 patients (46%) were assigned to the CAL (KD-CAL) group and 122 (54%) patients were assigned to the non-CAL (KD-nCAL) group. The levels of red blood cell count, red blood cell distribution width (RDW), C-reactive protein, tumor necrosis factor-α (TNF-α), and interleukin-6 were significantly higher in the KD-CAL group than those in the KD-nCAL group (all p < 0.05). RDW and TNF-α were found as independent risk factors of CAL occurrence. The sensitivity and specificity of RDW, TNF-α, and RDW + TNF-α in predicting KD with CAL were 67.31% and 79.51%, 74.04% and 73.77%, and 79.81% and 80.33%, respectively.Conclusion: In conclusion, alterations in RDW and TNF-α levels can be used as novel biomarkers for early prediction of CAL in KD patients, although the differences in their absolute values were small and might not give any added value to echocardiography. What is Known: •Known risk factors of CAL in children with KD include male gender and delayed use of intravenous immune globulin. What is New: •Our current study identified that red blood cell distribution width (RDW) and tumor necrosis factor-α (TNF-α) are novel independent risk factors for predicting CAL combined with KD among patients. •The combination of these RDW and TNF-α together shows higher sensitivity and specificity than either one used alone.

Serum microRNAs as novel biomarkers for early prediction of disease severity in patients with acute pancreatitis

BackgroundDysregulated microRNAs (miRNAs) have been identified to be associated with various diseases. However, the relationship between serum miRNAs and the severity of acute pancreatitis (AP) remains unknown.MethodsOne hundred twenty-five patients were enrolled and classified into mild AP (MAP, n = 45), moderate severe AP (MSAP, n = 42) and severe AP (SAP, n = 38) groups according to Atlanta 2012. TaqMan low density array (TLDA) technology was initially used in three pooled serum samples from 10 MAP, 10SAP and 10 healthy controls (HCs). The selected miRNAs were subsequently measured individually using quantitative real-time polymerase chain reaction (qRT-PCR) assay.ResultsThe TLDA identified 395 miRNAs were differentially expressed between the AP patients and the HCs, among which 12 miRNAs were selected for further evaluation. qRT-PCR confirmed that miR-19a, miR-143 and miR-374-5p were significantly upregulated in AP patients (p < 0.001) and increased with disease severity (p < 0.05). Receiver operating characteristic (ROC) curve analysis revealed that three miRNAs could distinguish the SAP patients from the HCs (area under ROC, AUC 0.940–0.943), MAP (AUC 0.754–0.782), and moderate severe AP (MSAP, AUC 0.670–0.686). In addition, multivariate logistic regression revealed that increased serum miR-143 was an independent predictor of developing SAP among MSAP and SAP patients (OR = 6.8, 95% CI 2.0–22.7) and among all AP patients (OR = 4.5, 95% CI 1.8–10.9).ConclusionsThese data indicate that an expression signature of three serum miRNAs holds potential as a novel biomarker for the early prediction of SAP.

Diagnostic Role of Plasma MicroRNA-21 in Stable and Unstable Angina Patients and Association with Aging.

The present study explored the clinical value of plasma microRNA-21 as a novel biomarker for early prediction of stable and unstable angina patients and its relationship with aging. A total of 255 participants, 123 patients with chronic stable angina, 82 patients with unstable angina, and 50 healthy subjects, were included in our study. Stable coronary and unstable coronary patients were confirmed following AHA/ACC clinical protocols. Total RNA was extracted from plasma by using miRNA-based TRIzol reagent. Plasma miR-21 expression levels were determined by real-time polymerase chain reaction. To evaluate the diagnosis accuracy, the receiver operating characteristic (ROC) curves were used. Plasma microRNA-21 concentration levels were significantly elevated in stable and unstable angina patients as compared with control subjects (P < 0.001). The area under the ROC curves of circulating microRNA-21 was accurately distinguished in stable angina patients (AUC 0.921) and unstable angina patients (AUC 0.944) from healthy subjects. MicroRNA-21 expression gradually elevated with increasing aging in all the populations. Moreover, the current study also demonstrated that the expression of plasma miR-21 levels was significantly associated with different age groups within healthy subjects and stable and unstable angina patients (P < 0.001). This research finding suggested that plasma microRNA-21 may be considered as a suitable new biomarker for early detection of stable and unstable angina patients, and it has a strong correlation with aging.

Cell-Free Fetal DNA: A Novel Biomarker for Early Prediction of Pre-eclampsia and Other Obstetric Complications

Hypertensive disorder of pregnancy, especially Pre-eclampsia is one of the major causes of increased maternal and perinatal morbidity and mortality all over the world. Early prediction of pre-eclampsia is the need of modern obstetrics, as this can timely prevent the progress of disease as well as related fetal and maternal morbidity and mortality. In addition to the screening of fetal aneuploidies, Rhesus-D status, fetal sex, single gene disorders, the cell-free fetal Deoxyribonucleic acid (DNA) quantification has emerged as a promising biomarker for the prediction of pre-eclampsia. Hence, its use can help in the early prediction of hypertensive disorders of pregnancy, especially pre-eclampsia even before the appearance of symptoms. Furthermore, in future, it can also help in the determination of the complete DNA sequence of every gene of the fetus. The present review focuses on recent literature concerning the use of cell-free fetal DNA in early prediction of preeclampsia as well as for non-invasive prenatal genetic screening of fetus for various disorders. Methods: The recent literature related to cell-free fetal DNA was searched from numerous English language journals and published peer-reviewed articles on Pubmed, Google Scholar, MEDLINE and various government agencies till 2016.

Early prediction of liver carcinogenicity due to occupational exposure to pesticides

Several studies linked between pesticides exposure and development of liver cancer, through several mechanisms inform of genotoxicity, cytotoxicity, tumor promotion, immunotoxicity and hormonal actions. This study aimed to estimate novel biomarkers for early prediction of liver malignancy due to occupational exposure to pesticides in two groups of workers with different socioeconomic standard (highly educated urban researchers and low educated rural pesticides sprayers). This study included 50 urban researchers and 50 rural pesticides sprayers occupationally exposed to pesticides. They were compared with 50 non-exposed urban researchers and 50 non-exposed rural subjects. Several tumor biomarkers were estimated; P53 protein, Alfa fetoprotein (AFP), and Alpha-L-fucosidase (AFU). Additionally, telomerase enzyme activity, Relative telomere length (RTL), and DNA damage using comet assay were measured. Furthermore, the glutathione-S-Transferase (GST) gene polymorphisms were identified for both exposed groups. Statistical analysis revealed elevated level of tumor biomarkers among exposed subjects relative to control groups in spite of being within the normal range. Increase in the DNA damage was detected, with shortening of telomere length and decrease in telomerase enzyme activity in pesticides-exposed subjects compared to their controls. Most of these changes were related to the levels of butyrylcholinesterase. Subjects with GSTT1 genotype were suggested to be more susceptible to hepatic carcinogenicity. Telomere relative length and comets assay together with GST genes polymorphisms could be used as early predictors for liver cancer susceptibility among pesticides exposed workers.

Weight Loss and Exercise Alter the High-Density Lipoprotein Lipidome and Improve High-Density Lipoprotein Functionality in Metabolic Syndrome.

High-density lipoprotein (HDL) lipid composition and function may better reflect cardiovascular risk than HDL cholesterol concentration. This study characterized the relationships between HDL composition, metabolism, and function in metabolic syndrome (MetS) patients and how changes in composition after weight loss (WL) and exercise treatments are related to function. Plasma samples from MetS patients (n=95) and healthy individuals (n=40) were used in this study. Subsets of the MetS group underwent 12 weeks of no treatment (n=17), WL (n=19), or WL plus exercise (WLEX; n=17). HDL was isolated using density-gradient ultracentrifugation. The HDL lipidome was analyzed by mass spectrometry, and particle size determined by nuclear magnetic resonance. Cholesteryl ester transfer protein activity and ex vivo HDL cholesterol efflux capacity (CEC) were assessed. The HDL lipidome in the MetS patients was substantially different from that in healthy individuals, mean particle size was smaller, and CEC was lower. Several HDL phospholipid and sphingolipid species were associated with HDL diameter and CEC. The HDL lipidome and particle size were modified toward the healthy individuals after WL and WLEX treatments, with greater effects observed in the latter group. Cholesteryl ester transfer protein activity was reduced after WL and WLEX, and CEC was improved after WLEX. WLEX treatment in MetS patients normalizes the HDL lipidome and particle size profile and enhances CEC. HDL lipids associated with diminished CEC may represent novel biomarkers for early prediction of HDL dysfunction and disease risk and may represent potential therapeutic targets for future HDL therapies. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00163943.

BCL6 mediates the effects of Gastrodin on promoting M2-like macrophage polarization and protecting against oxidative stress-induced apoptosis and cell death in macrophages

Cerebral palsy (CP) is the most common childhood disability worldwide, yet biomarkers for predicting CP are lacking. By subjecting peripheral blood samples from 62 CP patients and 30 healthy controls to Affymetrix GeneChip® PrimeView™ HumanGene Expression Microarray analysis, we identified the novel biomarker B-cell lymphoma 6 (BCL6) as the most upregulated gene in the CP samples. Gastrodin is a traditional Chinese medicine and bioactive compound that promotes adductor angle release, as well as gross and fine motor performance by increasing Gross Motor Function Measure-66 and Fine Motor Function Measure-45 scores. Gastrodin upregulates the mRNA expression of Mgl2 and Mrc1, M2 macrophage markers, and arginase activity, an M2 polarization indicator, in murine RAW264.7 macrophages. Moreover, these effects were blocked by BCL6 siRNA, which also abrogated the protective effects of Gastrodin against hydrogen peroxide-induced apoptosis and death in RAW264.7 cells. Our work identified BCL6 as a novel biomarker for early prediction of CP. Moreover, we demonstrated that Gastrodin not only stimulated polarization toward M2-like macrophages, which promote tissue repair, but also rescued macrophages from oxidative stress, apoptosis and death by inducing BCL6 expression. BCL6-targeted therapeutic strategies have promise for improving motor performance in CP patients.

The decreased PKM2 contributes to the survival of pancreatic cancer cells in hypoglucose by promoting autophagy

s / Pancreatology S18 microRNAs (miRNAs) in serum have been identified to be associated with various diseases. Here, we explored serummiRNAs as novel biomarkers for early prediction of the severity of AP. Methods: Serum samples were taken from 102 AP patients on admission and 40 controls. Patients were subclassified into mild AP (MAP, 36), moderately severe AP (MSAP, 35) and severe AP (SAP, 31) according to the revised Atlanta classification. TaqMan Low Density Arrays (TLDA) technology was performed initially in three pooled serum samples from 10 MAP, 10 SAP and 10 controls respectively. A hydrolysis probee based stemeloop quantitative reverse-transcription PCR (RT-qPCR) assay was conducted to confirm the concentrations of selected miRNAs in all individual serum samples (including the samples performed TLDA). Results: The TLDA revealed 24 serum miRNAs that dysregulated in AP patients compared with controls and altered more markedly in SAP than MAP. RT-qPCR analysis validated that miR-19a and miR-216a were significantly upregulated in AP patients (P <0.001) and correlated positively with the severity (P <0.05). The areas under receiver operating characteristic curve for miR-19a and miR-216a were 0.72 (P 1⁄40.001) and 0.73 (P <0.001) among all AP patients, higher than CRP (0.71, P 1⁄40.001) and APACHE II (0.70, P 1⁄40.001). Conclusions: Serum miR-19a and miR-216a might be served as novel biomarkers for early prediction of SAP.

Serum miR-19a and miR-216a as novel biomarkers for early prediction for the severity of acute pancreatitis

Serum miR-19a and miR-216a as novel biomarkers for early prediction for the severity of acute pancreatitis

Novel biomarkers for early prediction of sepsis-induced disseminated intravascular coagulation in a mouse cecal ligation and puncture model

IntroductionThe objective of this study was to identify biomarkers of sepsis-induced disseminated intravascular coagulation (DIC) among platelet-derived factors using biotin label-based custom protein microarray technology in a mouse cecal ligation and puncture (CLP) model.MethodsKM mice were randomized into sham-operated and CLP groups. Blood samples were obtained immediately and at 1 h, 2 h, 6 h, 12 h, 24 h, 48 h and 72 h after establishment of the CLP for platelet count, coagulation assay and blood chemistry. Lung and mesentery tissues were examined histologically at all corresponding time points, looking for microthrombus formation. Serial protein microarray analysis was performed to detect platelet-derived factors.ResultsThe survival rate 72 h post-CLP was 15%, but there was no mortality among the sham-operated mice. Compared with the sham group, the platelet count (n = 5, p < 0.05), fibrinogen concentration (n = 5, p < 0.05) and alanine aminotransferase level of the CLP group began to decrease significantly at 6 h post-CLP. Significant prolongation of prothrombin time (n = 5, p < 0.05) and activated partial thromboplastin time (n = 5, p < 0.05) and elevation of D-dimer (n = 5, p < 0.05) occurred after 6 h post-CLP. On histology, microthrombus formation in lung and mesentery tissue was observed in the CLP groups 6 h post-CLP and had become significant and extensive 12 h post-CLP (n = 5, p < 0.05). On protein microarray analysis and ELISA, thrombospondin (TSP), tissue inhibitor of metalloproteinase 1 (TIMP-1) and thymus chemokine-1 (TCK-1) all increased during the first 2 h post-CLP, then remained at a higher level than in the sham group for 72 h post-CLP (n = 5, p < 0.05).ConclusionsTSP, TIMP-1 and TCK-1 are elevated in the early stage of sepsis-induced DIC in a mouse CLP model and may be considered early markers for sepsis-induced DIC.