Useful Biomarker For Early Diagnosis Research Articles

D-dimer as a Useful Biomarker in Early Diagnosis of Neonatal Sepsis: A Single-Center Study From Romania.

This study evaluates the role of D-dimer in identifying neonatal sepsis and their potential value in clinical decision-making due to challenges in early detection. A case-control study was conducted on 102 neonates at the Children's Clinical Hospital "Louis Turcanu" in Timisoara, Romania, from October 2018 to July 2023. The participants were divided into two groups: those with neonatal sepsis and those without sepsis. The study found that neonates with sepsis were more likely to be delivered by cesarean section and had higher rates of premature ruptured membranes compared to those without sepsis. The D-dimer biomarker's predictive value for sepsis was assessed using a receiver operating characteristic (ROC) curve, with an area under the curve (AUC) exceeding 0.982 and an optimum cutoff value of 342 ng/mL. An increase in neonatal D-dimer significantly increases the likelihood of sepsis by 2.7% per unit increase. A value above 250 ng/mL indicates a 127-fold increased likelihood of sepsis. The D-dimer's ability to predict mortality innewborns with sepsis is unsatisfactory, with an AUC of 0.528. D-dimer, a potential biomarker of neonatal sepsis, warrants further clinical investigation to enhance diagnostic sensitivity and specificity, demonstrating its potential in conjunction with other sepsis markers.

Stage-Specific Alteration and Prognostic Relationship of Serum Fumarate Hydratase Autoantibodies in Gastric Cancer.

The relationship between energy production and cancer is attracting attention. This study aimed to investigate the clinicopathological significance of fumarate hydratase (FH), a tricarboxylic acid cycle enzyme, in gastric cancer using autoantibodies as biomarkers. The study analyzed 116 patients who underwent gastric cancer surgery and 96 healthy controls. Preoperative serum FH autoantibody (s-FH-Ab) titers were analyzed using an immunosorbent assay with an amplified luminescent proximity homogeneous assay. Receiver operating characteristic analysis was used to determine the cutoff s-FH-Ab titer. Clinicopathological factors and prognosis were compared between the high and low s-FH-Ab groups. The s-FH-Ab levels were significantly higher in the gastric cancer group than in the control group (p = 0.01). Levels were elevated even in patients with stage I gastric cancer compared with healthy controls (p = 0.02). A low s-FH-Ab level was significantly associated with distant metastasis (p = 0.01), peritoneal dissemination (p < 0.05), and poor overall survival (p < 0.01). Multivariate analysis revealed that low s-FH-Ab levels were an independent risk factor for poor prognosis (p < 0.01). Therefore, s-FH-Ab levels may be a useful biomarker for early diagnosis and the prediction of prognosis in patients with gastric cancer.

Potential clinical applications of extracellular vesicles in pancreatic cancer: exploring untapped opportunities from biomarkers to novel therapeutic approaches

Pancreatic cancer is a highly lethal and metastatic malignancy, mainly because it often remains undetected until advanced stages due to the limitations of current diagnostic methods, rendering currently available therapies ineffective. Therefore, it is imperative to identify useful biomarkers for early diagnosis and new therapeutic targets for pancreatic cancer. Recently, extracellular vesicles have emerged as promising biomarkers for the diagnosis and prognosis of pancreatic cancer. Given their presence in various bodily fluids, extracellular vesicles offer a non-invasive approach through liquid biopsy to detect and monitor cancer progression. In this review, we comprehensively examine the multifaceted roles of extracellular vesicles in the progression of cancer, while also exploring their potential as diagnostic, prognostic, and therapeutic biomarkers in the context of pancreatic cancer.

Comparison of rapid dengue NS1, qualitative ELISA, and quantitative ELISA result

Background: Non-structural glycoprotein-1 (NS1) is a useful biomarker for early diagnosis of dengue fever. NS-1 antigen ELISA can be used for the early diagnosis of dengue fever in the acute stage. Quantitative methods are better for epidemic settings due to high false negative rates in qualitative ELISA. Methods: The study was initiated after approval from the institutional ethics council (IEC/DISS/17118). Study examined 280 patients with dengue symptoms who presented to the hospital's OPDs and IPDs. Patients were tested using qualitative ELISA, and those with Leptospira antibody, malaria, or Chikungunya IgM antibody were excluded. Age, gender, symptoms, comorbidities, total leucocyte count, platelet count, and risk category were all patient-related parameters. Patient-related parameters were recorded, and data was collected using Microsoft excel and analysed statistically. Results: Most patients aged 2-40 with male predominance had fever, chills, and body aches, 243 (86.8%) tested positive for ELISA NS1. Quantitative ELISA test showed a statistically significant correlation with rapid antigen NS1 result (p=0.015). Its AUC was 0.883 (p=0.0001), and its cut-off was (&gt;109.1) with 96.9% sensitivity and 13.64% specificity. The AUC of quantitative ELISA NS1 against qualitative ELISA NS1 was 0.853 which was statistically significant (p&lt;0.0001). At the cut-off &gt;74.34, the test's sensitivity was 92.59% and specificity was 75.68%. Conclusions: Qualitative ELISA NS1 test is better than rapid antigen test for screening due to its higher specificity and similar sensitivity.

Immature Platelet Fraction and Acute Coronary Syndrome; a Systematic Review and Meta-Analysis.

Immature Platelet Fraction (IPF) is a measure of the proportion of reticulated platelets (RPs) to all platelets in circulation. IPF may have both prognostic and diagnostic values in patients with Acute Coronary Syndrome (ACS). This study aims to comprehensively summarize the diagnostic utility of IPF levels in patients with ACS, specifically focusing on its ability to differentiate between different subtypes of ACS. We conducted a systematic search in online databases including MEDLINE, Scopus, and Google Scholar up to March 4th 2024, to identify relevant studies. The random-effect model, employing inverse variance for mean differences (MD) and Mantel-Haenszel methods for odds ratios (OR) were utilized to combine the data. Joanna Briggs Institute (JBI) appraisal tool was employed to assess the quality of included studies. Our systematic review contains 15 articles with a total sample size of 2,030 ACS patients. Pooled analysis revealed significant differences in IPF levels of ACS patients compared to healthy controls (MD (95%CI): 2.85 (0.86, 4.85), P-value = 0.004) and stable angina patients (MD (95%CI): 0.58 (0.23, 0.92), P-value < 0.001). Subgroup comparisons within ACS patients demonstrated higher IPF levels in myocardial infarction (MI) vs. unstable angina (UA) (MD (95%CI): 1.81 (0.41, 3.22), P-value = 0.01), ST elevation MI (STEMI) vs. non-ST elevation (NSTEMI) ACS (MD (95%CI): 0.74 (0.31, 1.17), P-value < 0.001), and NSTEMI vs. UA (MD (95% CI): 1.07 (0.24, 1.90), P-value = 0.01). IPF levels could increase in patients with ACS, particularly during the acute phase of STEMI. This suggests that IPF may be a useful biomarker for early diagnosis of ACS. Additionally, IPF levels may help differentiate between ACS subtypes.

A dual-mode method for detection of miRNA based on the photoluminescence and resonance light scattering

MicroRNAs (miRNAs) hold potential as useful biomarkers for early diagnosis and evaluation of diverse cancers, but their low abundance and short length make the detection of miRNAs face low sensitivity and accuracy. Herein, a photoluminescence (PL)-resonance light scattering (RLS) dual-mode method was developed for the sensitive and accurate detection of miRNA-141 using CdTe quantum dots (QDs) and Au nanoparticles. The presence of miRNA-141 induced PL quenching and RLS increasing. The limit of detection (LOD) was as low as 3.7 fM, and the miRNA-141 was detected linearly in a range from 10 fM to 10 nM. The dual signals generated no mutual interference and were detected using the same spectrophotometer, allowing for mutual validation to ensure the accuracy and reliability of the detection results. This study proposes valuable references for constructing dual-mode detection methods.

B-054 Potential of Autotaxin in the Early Diagnosis of Sinusoidal Obstruction Syndrome after Allogeneic Hematopoietic Cell Transplantation

Abstract Background Sinusoidal obstruction syndrome (SOS) is a life-threatening complication after allogeneic hematopoietic cell transplantation (allo-HCT). Early intervention leads to a good prognosis, but it is often difficult to differentiate SOS from other hepatobiliary complications. Liver biopsy is the gold standard for diagnosing SOS, but it is difficult to perform invasive testing early in the transplant process, and no specific biomarker for SOS has been established. Autotaxin (ATX) is useful as a liver fibrosis marker, the serum levels of which are elevated by metabolic inhibition of liver sinusoidal endothelial cells. Considering the pathophysiology of SOS, which begins with injury of liver sinusoidal endothelial cells, serum ATX levels may be elevated early in the onset of SOS. Methods A retrospective study was conducted of 247 patients who had received allo-HCT, including 11 patients who developed SOS and met the EBMT criteria (male, 7; female, 4). Of 11 patients with SOS, 9 had pathologically proven SOS. The median time from allo-HCT to SOS diagnosis was 31 days (range, 8–141 days [male], 16–31 days [female]). This cohort included 39 patients with hepatobiliary complications without SOS (total bilirubin &amp;gt; 2 mg/dL; male, 23; female, 16). Serum ATX levels were measured in stored samples before conditioning and at days 1, 3, 5, 7, 14, 28, 60, 90, 180, and 365 after allo-HCT by a two-site enzyme immunoassay with an AIA-2000 analyzer. The area under the receiver operating characteristic (AUROC) of serum ATX levels for the diagnosis of SOS was analyzed. Results We first investigated the variability of serum ATX levels during the allo-HCT period. Serum ATX levels fluctuated as follows: decreased on day 1, increased and peaked on days 7–14, and then decreased again on days 28–60. A variety of factors associated with allo-HCT such as the conditioning regimen and administration of steroids affected serum ATX levels. Serum ATX levels before and after allo-HCT tended to be higher in patients with SOS. In male patients, the AUROCs of serum ATX levels on day 3 after allo-HCT were 0.75 (in all patients; 95% confidence interval [95%CI], 0.49–1.00) and 0.75 (in patients with hepatobiliary complications; 95%CI, 0.48–1.00). In female patients, the AUROCs of serum ATX levels on day 14 after allo-HCT were 0.88 (in all patients; 95%CI, 0.77–0.98) and 0.94 (in patients with hepatobiliary complications; 95%CI, 0.82–1.00). These findings indicated that serum ATX levels before the diagnosis of SOS had a diagnostic capacity. In addition, focusing on severe SOS cases, three of six patients had serum ATX levels above the upper reference limit before conditioning (a total of 18 patients exceeded the upper reference limit in this cohort). Of the remaining three patients, two had elevated post-transplant ATX levels near or above the upper reference limit prior to diagnosis of SOS. Conclusion Although validation by further studies with larger numbers of SOS cases is needed, the serum ATX level may be a useful biomarker for early diagnosis of SOS after allo-HCT.

SSNA1 Promotes Hepatocellular Carcinoma Metastasis Via STAT3/EMT Induction.

Hepatocellular carcinoma (HCC) currently represents the third most prevalent cause of cancer-related deaths globally. HCC is typically diagnosed at advanced stages with metastasis, and has a poor outcome. In order to identify useful biomarkers for early diagnosis and develop novel therapeutic targets, it is necessary to better understand the cellular mechanisms driving HCC progression. Public datasets were used to detect Sjögren's syndrome nuclear autoantigen-1 (SSNA1) expression in HCC. Scratch assay and transwell invasion assays were used to evaluate the migration and invasion ability of HCC cells. We explored the molecular mechanism by western blotting, viability and transfection assays. SSNA1 was found up-regulated in human HCC tissues. SSNA1 expression increased along with HCC progression. In addition, elevated SSNA1 expression in HCC patients was closely correlated to a poor prognosis. The proliferation and apoptosis of HCC cells were unaffected by reducing SSNA1 expression. Meanwhile, STAT3/EMT axis inhibition mediated by SSNA1 depletion prevented HCC cells from migrating and invading in vitro. SSNA1 could be used as a biomarker for HCC diagnosis and prognosis, and point the direction for the future investigation of innovative approaches to target and treat HCC.

The tear cytokine panel is a useful biomarker for early diagnosis and severity-evaluating of ocular chronic graft-versus-host disease.

The tear cytokine panel is a useful biomarker for early diagnosis and severity-evaluating of ocular chronic graft-versus-host disease.

Predictive Value of Annenxin A1 for Disease Severity and Prognosis in Patients with Community-Acquired Pneumonia.

This prospective, single-center study evaluated the clinical utility of annenxin (Anx)A1 level as a biomarker for determining the severity of illness and predicting the risk of death in hospitalized patients with community-acquired pneumonia (CAP). A total of 105 patients (53 with severe [S]CAP, 52 with non-SCAP) were enrolled from December 2020 to June 2021. Demographic and clinical data were recorded. Serum AnxA1 concentration on days one and six after admission was measured by enzyme-linked immunosorbent assay. AnxA1 level at admission was significantly higher in SCAP patients than in non-SCAP patients (p < 0.001) irrespective of CAP etiology and was positively correlated with Pneumonia Severity Index and Confusion, Uremia, Respiratory Rate, Blood Pressure, and Age ≥ 65 Years score. AnxA1 level was significantly lower on day six after treatment than on day one (p = 0.01). Disease severity was significantly higher in patents with AnxA1 level ≥254.13 ng/mL than in those with a level <254.13 ng/mL (p < 0.001). Kaplan-Meier analysis of 30-day mortality showed that AnxA1 level ≤670.84 ng/mL was associated with a significantly higher survival rate than a level >670.84 ng/mL. These results indicate that AnxA1 is a useful biomarker for early diagnosis and prognostic assessment of CAP.

Utility of transforming growth factor beta-1 in diagnosis of neonatal necrotizing enterocolitis.

Necrotizing enterocolitis (NEC) yet remains a leading cause of morbidity and mortality in premature infants. The developmental deficiency of transforming growth factor-Beta (TGF-β) in the intestine is a risk factor for NEC in premature infants.We aimed to investigate the potential utility of serum TGF-β1 in the early diagnosis and severity assessment of NEC. This prospective case-control study was conducted on 102 VLBW neonates aging less than 32 weeks and weighing less than 1500 gm. They were divided into NEC group of 52 preterm neonates with symptoms and signs of NEC and 50 age and sex-matched neonates without NEC as a control group. All neonates underwent full medical history taking, clinical examination, radiological and laboratory investigations including CBC, CRP, fecal occult blood, and serum TGF-β1. Serum TGF-β1 was tested in NEC patients at the onset of symptoms and signs and 7 days later. Serum TGF-β1 was significantly lower in NEC patients at the onset of symptoms than the control group (P = 0.004) while after 7 days of onset serum TGF-β1 was significantly higher than at the onset of symptoms (P < 0.001). In NEC patients with stage I, TGF-β1 was significantly higher than in NEC patients with stage ≥II (P = 0.027).In conclusion serum TGF-β1 is downregulated in neonatal necrotizing enterocolitis and can be used as a useful biomarker for early diagnosis of NEC and to assess disease severity.

The Plasma DIA-Based Quantitative Proteomics Reveals the Pathogenic Pathways and New Biomarkers in Cervical Cancer and High Grade Squamous Intraepithelial Lesion

The process of normal cervix changing into high grade squamous intraepithelial lesion (HSIL) and invasive cervical cancer is long and the mechanisms are still not completely clear. This study aimed to reveal the protein profiles related to HSIL and cervical cancer and find the diagnostic and prognostic molecular changes. Data-independent acquisition (DIA) analysis was performed to identify 20 healthy female volunteers, 20 HSIL and 20 cervical patients in a cohort to screen differentially expressed proteins (DEPs) for the HSIL and cervical cancer. Subsequently, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were used for functional annotation of DEPs; the protein-protein interaction (PPI) and weighted gene co-expression network analysis (WGCNA) were performed for detection of key molecular modules and hub proteins. They were validated using the Enzyme-Linked Immunosorbent Assay (ELISA). A total of 243 DEPs were identified in the study groups. GO and KEGG analysis showed that DEPs were mainly enriched in the complement and coagulation pathway, cholesterol metabolism pathway, the IL-17 signaling pathway as well as the viral protein interaction with cytokine and cytokine receptor pathway. Subsequently, the WGCNA analysis showed that the green module was highly correlated with the cervical cancer stage. Additionally, six interesting core DEPs were verified by ELISA, APOF and ORM1, showing nearly the same expression pattern with DIA. The area under the curve (AUC) of 0.978 was obtained by using ORM1 combined with APOF to predict CK and HSIL+CC, and in the diagnosis of HSIL and CC, the AUC can reach to 0.982. The high expression of ORM1 is related to lymph node metastasis and the clinical stage of cervical cancer patients as well as the poor prognosis. DIA-ELSIA combined analysis screened and validated two previously unexplored but potentially useful biomarkers for early diagnosis of HSIL and cervical cancer, as well as possible new pathogenic pathways and therapeutic targets.

Surfactant Protein D Level in Cement Workers

Background: Pneumoconiosis occurs almost all in entire worldwide. Pneumoconiosis had threatened cement workers. Serologic abnormalities had found in pneumoconiosis. Surfactant Protein D (SP-D) levels increased in silica exposed workers. Surfactant Protein D (SP-D) may be useful biomarkers for early diagnosis of pneumoconiosis but it has not yet been studied in Indonesia.Method: This is a cross-sectional study and was done by consecutive sampling. The total subject was 61, consisting of 44 cement exposed workers and 17 control from September 2017–March 2018. Serum level of SP-D was measured by ELISA method. Cement exposed workers are a worker in the production area in workers in quarry areas.Results: This study found that total characteristic subjects were male 100% and mean of age was 42.5 years old, the youngest and oldest subject was 21 and 55 years old, respectively. Normal weight group's greatest number was found in 21 subjects (47.7%), followed by overweight 12 subjects (22.3%), obese 8 subjects (18.2%), and underweight 1 subject (2.3%). Based on a history of smoking, this study found that 26 subjects (59.1%) had never smoked, 12 subjects (27.3%) as smokers, and 6 subjects (13.6%) as former smokers. Duration of exposure &lt;10 years was found in 9 subjects (20.5%) and duration of exposure ≥10 years was found in 35 subjects (79.5%) with using self-respiratory safety instrument as good categorical 5 subjects (11.4%), moderate categorical 36 subjects (81.8%) and poor in quality categorical 3 subjects were found (6.8%). Mean of serum SP-D levels in exposed group was found that 111.027 ng/ml and mean of serum SP-D levels in control group was found that 67.648 ng/ml. Levels of serum SP-D were significantly higher in exposed group than control group (p-value=0.014).Conclusion: Comparison serum SP-D levels between exposed group and control group statistically higher in exposed group than control group.

Serum Proteomic Analysis Identifies SAA1, FGA, SAP, and CETP as New Biomarkers for Eosinophilic Granulomatosis With Polyangiitis

BackgroundEosinophilic granulomatosis with polyangiitis (EGPA) is characterized by asthma-like attacks in its early stage, which is easily misdiagnosed as severe asthma. Therefore, new biomarkers for the early diagnosis of EGPA are needed, especially for differentiating the diagnosis of asthma.ObjectivesTo identify serum biomarkers that can be used for early diagnosis of EGPA and to distinguish EGPA from severe asthma.MethodData-independent acquisition (DIA) analysis was performed to identify 45 healthy controls (HC), severe asthma (S-A), and EGPA patients in a cohort to screen biomarkers for early diagnosis of EGPA and to differentiate asthma diagnosis. Subsequently, parallel reaction monitoring (PRM) analysis was applied to a validation cohort of 71 HC, S-A, and EGPA patients.ResultFour candidate biomarkers were identified from DIA and PRM analysis—i.e., serum amyloid A1 (SAA1), fibrinogen-α (FGA), and serum amyloid P component (SAP)—and were upregulated in the EGPA group, while cholesteryl ester transfer protein (CETP) was downregulated in the EGPA group compared with the S-A group. Receiver operating characteristics analysis shows that, as biomarkers for early diagnosis of EGPA, the combination of SAA1, FGA, and SAP has an area under the curve (AUC) of 0.947, a sensitivity of 82.35%, and a specificity of 100%. The combination of SAA1, FGA, SAP, and CETP as biomarkers for differential diagnosis of asthma had an AUC of 0.921, a sensitivity of 78.13%, and a specificity of 100%, which were all larger than single markers. Moreover, SAA1, FGA, and SAP were positively and CETP was negatively correlated with eosinophil count.ConclusionDIA-PRM combined analysis screened and validated four previously unexplored but potentially useful biomarkers for early diagnosis of EGPA and differential diagnosis of asthma.

Presepsin as a predictor of septic shock in patients with urinary tract infection

BackgroundRecently, presepsin has been reported to be a useful biomarker for early diagnosis of sepsis and evaluation of prognosis in septic patients. However, few reports have evaluated its usefulness in patients with urinary tract infections (UTI). This study aimed to evaluate whether presepsin could be a valuable marker for detecting severe sepsis, and whether it could predict the therapeutic course in patients with UTI compared with markers already used: procalcitonin (PCT) and C-reactive protein (CRP).MethodsFrom April 2014 to December 2016, a total of 50 patients with urinary tract infections admitted to Gunma university hospital were enrolled in this study. Vital signs, presepsin, PCT, CRP, white blood cell (WBC) count, causative agents of urinary-tract infections, and other data were evaluated on the enrollment, third, and fifth days. The patients were divided into two groups: with (n = 11) or without (n = 39) septic shock on the enrollment day, and with (n = 7) or without (n = 43) sepsis on the fifth day, respectively. Presepsin was evaluated as a biomarker for systemic inflammatory response syndrome (SIRS) or septic shock.ResultsRegarding the enrollment day, there was no significant difference of presepsin between the SIRS and non-SIRS groups (p = 0.276). The median value of presepsin (pg/mL) was significantly higher in the septic shock group (p < 0.001). Multivariate logistic regression analysis showed that presepsin (≥ 500 pg/ml) was an independent risk factor for septic shock (p = 0.007). ROC curve for diagnosing septic shock indicated an area under the curve (AUC) of 0.881 for presepsin (vs. 0.690, 0.583, and 0.527 for PCT, CRP and WBC, respectively). Regarding the 5th day after admission, the median presepsin value on the enrollment day was significantly higher in the SIRS groups than in the non-SIRS groups (p = 0.006). On the other hand, PCT (≥ 2 ng/ml) on the enrollment day was an independent risk factor for SIRS. ROC curve for diagnosing sepsis on the fifth day indicated an AUC of 0.837 for PCT (vs. 0.817, 0.811, and 0.802 for presepsin, CRP, and WBC, respectively).ConclusionsThis study showed that presepsin may be a good marker for diagnosing septic shock based on admission data in patients with UTI.

Analytical and clinical performance of the Advansure i3 procalcitonin assay

Procalcitonin (PCT) is a clinically useful biomarker for early diagnosis and subsequent management of sepsis. We evaluated the analytical performance of a new automated chemiluminescent immunoanalyzer-based procalcitonin assay, AdvanSure i3 PCT assay (LG Life Sciences, Korea) on an AdvanSure i3 (LG Life Sciences) and compared it to the Elecsys BRAHMS PCT assay (Roche, Switzerland) on a Cobas e801 (Roche). Analytical performance was performed for the precision, linearity, and method comparison with the Elecsys BRAHMS PCT assay by Clinical and Laboratory Standards Institute guidelines. Clinical evaluations were conducted using 87 residual samples from admitted patients with suspected infection. The patients were classified based on Sepsis-3 classification. The AdvanSure i3 PCT assay exhibited a CV <5.5% for between-run precision and <6.5% for within-laboratory precision. The assay was linear up to 80.32 µg/L (r = 0.990). Statistical analysis showed that the two assays yielded a good correlation (r = 0.996), with a weighted kappa value of 0.94. Median plasma PCT level was significantly different between the non-sepsis and sepsis groups (p < .001) and the non-sepsis and septic shock groups (p < .0018). The AdvanSure i3 PCT assay showed good analytical performance and correlation with the Elecsys BRAHMS PCT assay for the sepsis patients. This new assay can be used as a diagnostic early marker of sepsis in clinical laboratories.

Four plasma miRNAs act as biomarkers for diagnosis and prognosis of non-small cell lung cancer.

Previous studies have reported that the aberrant expression of circulating microRNAs (miRNAs/miRs) can be used as diagnostic and prognostic markers in non-small cell lung cancer (NSCLC). The present study aimed to assess the diagnostic and prognostic predictive values of four plasma miRNAs for NSCLC. A total of 12 candidate miRNAs were selected that have previously been reported to be aberrantly expressed in NSCLC, and their plasma levels in the training set were detected via reverse transcription-quantitative PCR analysis. The screened out miRNAs were further validated in the testing set. The area under the curve (AUC) of the receiver operating characteristic curve was constructed to evaluate diagnostic performance. Kaplan-Meier survival analysis was performed to assess the association between the plasma miRNA levels and disease-free survival (DFS) time. The results demonstrated that 4/12 plasma miRNAs (miR-210, miR-1290, miR-150 and miR-21-5p) were highly expressed in patients with NSCLC compared with their expression levels in patients with benign lung disease (BLD) and healthy controls in the training and testing sets, respectively. The AUC values of the four-miRNA panel were 0.96 and 0.93 in the training and testing sets, respectively, for distinguishing patients with NSCLC from healthy controls, which were similar to the AUC values for distinguishing patients with NSCLC from patients with BLD (0.96 and 0.94). The AUC values of the four-miRNA panel in patients with stage I NSCLC were comparable to that of patients with stage II-III NSCLC (0.942 and 0.965). Patients with high plasma levels of miR-210 and miR-150 had worse DFS than those with low plasma levels of these miRNAs. In addition, patients whose plasma levels of the four miRNAs decreased by >50% after surgery exhibited a good DFS. Taken together, the results of the present study suggest that these four miRNAs (miR-210, miR-1290, miR-150 and miR-21-5p) act as useful biomarkers for early diagnosis and prognosis of NSCLC.

Urinary cystatin C as a biomarker of early renal dysfunction in type 2 diabetic patients

AimsWe aimed to evaluate urinary CysC (cystanin c) as an early marker of diabetic nephropathy in patients with type 2 diabetes and investigate the correlation of urinary CysC with albuminuria and GFR. MethodologyThis case-controlled study was conducted on 66 type 2 diabetic patients who were classified according to albuminuria into 3 groups and consisting of 20 healthy subjects as the control group. We assessed urinary CysC, urinary albumin excretion rate (UACR). ResultsUrinary CysC levels were significantly higher in normoalbuminuric diabetic compared with healthy control and there was a progressive linear increase in urinary CysC levels with increasing albuminuria in the diabetic patients. Despite insignificant deference in creatinine between participants groups, we observed significant differences between these groups as regard eGFR, urinary CysC, and UACR. Urinary CysC did not have significant correlations with any clinical or biochemical parameters. Moreover, urinary CysC had a statistically significant association with albuminuria and eGFR. ConclusionUrinary CysC levels correlated with UACR and GFR. It is linked to subclinical tubular injury and can be an earlier marker of kidney involvement, even before albuminuria and it is less influenced by non-renal factors. Therefore, Urinary CysC is useful biomarker for early diagnosis of diabetic nephropathy.

Diagnostic Value of Circulating MicroRNAs for Middle Aged Coronary Artery Disease Patients: A Case-control Study

Introduction: Coronary Artery Disease (CAD) remains a major problem worldwide. New and useful biomarkers for early diagnosis are necessary. MicroRNAs (miR) are short, non-coding RNAs that post transcriptionally regulate gene expression through degradation and translational repression of mRNAs. Aim: The current case-control study was designed to assess strength and relevance of diagnostic miR-126, 122 and Vascular Endothelial Growth Factor (VEGF) level in the diagnoses of angiographically proven CAD cases. Materials and Methods: Circulating levels of miR-126 and miR-122 and VEGF levels were measured in serum from 100 middle aged 46-58 years patients with CAD and 100 patients without CAD through quantitative real-time polymerase chain reaction (qRT-PCR) analysis. Results: Circulating miR-122 level was significantly higher in CAD cases compared to control (1.60±1.06 and 0.93±0.43, p=0.001), however miR-126 was significantly lowered in CAD cases compared to control (0.82±0.51 and 1.01±0.47, p=0.02). Circulating VEGF level was significantly higher in CAD cases compared to control (182.97±156.49 and 105.49±103.88, p=0.02). Circulating miR-122, 126 and VEGF level did not show any association with demographic and clinical parameters. Area Under the Curve (AUC) for circulating miR-122, 126 and VEGF were 0.700, 0.644 and 0.649 with sensitivity and specificity of 66.67%, 56.41%, 61.18% and 70%, 60% and 64%, respectively. The combined diagnostic efficacy of miR-122 and 126 showed higher sensitivity and specificity. Conclusion: Circulating miR-122 and 126 might be novel, non-invasive biomarkers for early diagnosis of CAD. Further exposition of the role of miR-122, 126 and VEGF in the progression of CAD will add to the understanding of the disease process leading to a new diagnostic approach. However, further studies on larger patient cohorts are required to validate the findings.

The thromboelastography G parameter as a potential biomarker of acute coronary syndrome

The most prominent event that defines acute coronary syndrome (ACS) is the formation of an intra-arterial thrombus, usually resulting from activation of platelet and fibrinogen at the ruptured plaque. Usually, conventional coagulation tests (CCTs) are used to estimate the hemostatic properties of patients. However, CCTs have significant limitations because they each assess individual aspects of the coagulation cascade, which is a complex multifaceted process. And CCTs are performed with platelet-poor plasma, while the contribution of platelets to clot formation is not measured. In contrast, thromboelastography (TEG) is a test for global hemostasis with whole blood, from the beginning of coagulation through clot formation to the ending with fibrinolysis. The aim of this study was to investigate whether TEG parameters could be surrogate biomarkers of thrombus formation process and diagnosis of ACS. Receiver operating characteristic（ROC）curve was used to evaluate the diagnosis performance of each index. Logistic regression analysis was utilized to define the independent risk factors of ACS. The results showed that the shear elastic modulus parameter (G) was an independent diagnostic indicator for ACS (odds ratio [OR], 2.600; 95% confidence interval [CI], 2.035–3.322). The area under ROC curve of G was 0.866. The optimal cut-off value for the diagnosis of ACS was 10.55 dyne/cm2, while the sensitivity was 66.2% and the specificity was 92.4%. In conclusion, G could be used as an optimal indicator of activation of platelet and fibrinogen, which is eligible to be a useful biomarker for early diagnosis of ACS.