Diagnostic Biomarker In Patients Research Articles

Serum levels of circulating microRNA-107 are elevated in patients with early-stage HCC.

BackgroundEarly detection of hepatocellular carcinoma (HCC), the most common primary liver malignancy, is crucial to offer patients a potentially curative treatment strategy such as surgical resection or liver transplantation (LT). However, easily accessible biomarkers facilitating an early diagnosis of HCC as well as a reliable risk prediction are currently missing. The microRNA(miR)-107 has recently been described as a driver of HCC in both murine and human HCC but data on circulating miR-107 in HCC patients are scarce. In the present study, we evaluated a potential diagnostic and/or prognostic role of circulating miR-107 in patients undergoing tumor resection or LT for early-stage HCC.MethodsThe Kmplot bioinformatic tool was used to query publicly available databases (including TCGA, GEO and EGA) in order to analyse the prognostic value of tumoral miR-107 expression in HCC patients (n = 372). Serum levels of miR-107 were measured by qPCR in n = 45 HCC patients undergoing surgical tumor resection (n = 37) or LT (n = 8) as well as n = 18 healthy control samples. Results were correlated with clinical data.ResultsA high tumoral expression of miR-107 was associated with a significantly better overall survival compared to patients with low miR-107 expression levels (HR 0.69, 95% CI 0.48–0.99, p = 0.041). In addition, serum levels of miR-107 were significantly higher in HCC patients when compared to healthy controls. However, miR-107 serum levels in HCC patients were independent of different disease etiology, tumor stage or tumor grading. HCC patients with baseline miR-107 expression levels above a calculated ideal prognostic cut-off value (9.82) showed a clear trend towards an impaired overall survival (p = 0.119).ConclusionTumoral miR-107 expression levels are a potential prognostic marker in early stage HCC. Furthermore, we describe a potential role of circulating miR-107 levels as a diagnostic biomarker in patients with early-stage HCC.

Evaluation of serum ATX and LPA as potential diagnostic biomarkers in patients with pancreatic cancer

BackgroundPancreatic cancer (PC) is a devastating disease that has a poor prognosis and a total 5-year survival rate of around 5%. The poor prognosis of PC is due in part to a lack of suitable biomarkers that can allow early diagnosis. The lysophospholipase autotaxin (ATX) and its product lysophosphatidic acid (LPA) play an essential role in disease progression in PC patients and are associated with increased morbidity in several types of cancer. In this study, we evaluated both the potential role of serum LPA and ATX as diagnostic markers in PC and their prognostic value for PC either alone or in combination with CA19-9.MethodsATX, LPA and CA19-9 levels were evaluated using ELISA of serum obtained from PC patients (n = 114) healthy volunteers (HVs: n = 120) and patients with benign pancreatic diseases (BPDs: n = 94).ResultsSerum levels of ATX, LPA and CA19-9 in PC patients were substantially higher than that for BPD patients or HVs (p < 0.001). The sensitivity of LPA in early phase PC was 91.74% and the specificity of ATX was 80%. The levels of ATX, LPA and CA19-9 were all substantially higher for early stage PC patients compared to levels in serum from BPD patients and HVs. The diagnostic efficacy of CA19-9 for PC was significantly enhanced by the addition of ATX and LPA (p = 0.0012).ConclusionMeasurement of LPA and ATX levels together with CA19-9 levels can be used for early detection of PC and diagnosis of PC in general.

Prognostic Value and Molecular Mechanisms of Proteasome 26S Subunit, Non-ATPase Family Genes for Pancreatic Ductal Adenocarcinoma Patients after Pancreaticoduodenectomy

Objective: Pancreatic cancer (PC) is an extremely malignant tumor with similar morbidity and mortality and lack of an effective treatment. This study explored the prognostic value and molecular mechanisms of proteasome 26S subunit, non-ATPase (PSMD) family genes in pancreatic ductal adenocarcinoma (PDAC). Methods: Survival analyses were performed to elucidate the relationship between prognosis and the level of PSMD expression. ROC curves and nomograms were constructed to predict the prognosis. A bioinformatics analysis was used to explore the co-expression and complex interaction networks of PSMDs. The potential mechanisms were further explored via gene set enrichment analysis (GSEA). Results: We find high levels of PSMD6, PSMD9, PSMD11, and PSMD14 expression were significantly associated with a poorer OS. High PSMD6 and PSMD11 expression was associated with a poorer relapse-free survival (RFS). A risk score model was constructed based on prognosis-related genes. The area under ROC curves (AUC) was 53.3%, 59.3%, and 62.9% for 1-, 2-, 3 years, respectively. Conclusion: GSEA revealed that PSMD6 and PSMD11 play a role in PDAC through various biological processes and signaling pathways, including TP53, CDKN2A, MYC pathway, DNA repair, KRAS, cell cycle checkpoint, NIK, NF-κB signaling pathway, and proteasomes. This study demonstrated that PSMD6 and PSMD11 could serve as a potential prognostic and diagnostic biomarkers for patients with early-stage PDAC after pancreaticoduodenectomy.

Serum S100A8 as an early diagnostic biomarker in patients with community-acquired pneumonia

IntroductionLimited studies have suggested that calprotectin may take part in the pathophysiology of community-acquired pneumonia (CAP). Nevertheless, there is no clinical study analysing the role of S100A8 in CAP patients. The objective of this study was to analyse the association of serum S100A8 with the severity of CAP and determine the cut-off values of S100A8 for predictive power based on a cross-sectional study.Material and methodsA total of 200 CAP patients and 100 normal subjects were recruited. Demographic data, clinical information, and serum were collected on admission. S100A8 and inflammatory cytokines were detected using ELISA and RT-PCR. All statistical analyses were performed with SPSS 19.0.ResultsSerum S100A8 was increased in CAP patients on admission. Serum S100A8 was gradually increased in parallel with CAP severity scores. Serum S100A8 was positively correlated with CAP severity scores, blood routine parameters, and inflammatory cytokines. Furthermore, univariate and multivariate logistical regression revealed that there were positive associations between serum S100A8 with CRB-65, PSI, and CURXO. Moreover, the predictive capacity of serum S100A8 was determined by ROC curve analysis. The area under the curves of S100A8 for CAP and CAP severity were 0.855 and 0.893, respectively. Mechanistic analysis found that S100A8 knockdown alleviated streptococcus pneumoniae-evoked inflammatory cytokines in A549 cells.ConclusionsSerum S100A8 on admission was positively associated with the severity of CAP. S100A8 knockdown alleviates streptococcus pneumoniae-evoked inflammatory cytokines in A549 cells, indicating that S100A8 may exert a significant effect on the pathophysiology of CAP and could be an early serum diagnostic biomarker for CAP.

Identification and validation of potential novel biomarkers for oral squamous cell carcinoma

ABSTRACT Our study aimed to explore potential new diagnostic biomarkers in patients with oral squamous cell carcinoma (OSCC) to find new target molecules involved in the progression of OSCC. Potential novel biomarkers of OSCC were identified using a protein microarray assay. Compared with the healthy control group, there were five proteins (I309, GDF15, AXL, MMP3, and CTACK) in the serum of in situ oral cancer group. However, there were four differentially expressed proteins (MCSF, I309, MMP3, and CTACK) in the serum of the OSCC group. Receiver operating characteristic (ROC) curve analysis results suggested that these six proteins (I309, GDF15, AXL, MMP3, CTACK, and MCSF) had diagnostic value for OSCC. Based on The Cancer Genome Atlas (TCGA) database, we found that only GDF15 expression was associated with the prognosis of OSCC. Subsequently, we verified the expression levels of six proteins in HSC-3 and HaCaT cells, and the results showed that the level of these six proteins was significantly higher in HSC-3 cells than in normal HaCaT cells. Similarly, in the OSCC nude mouse model, the expression levels of these proteins were significantly upregulated in OSCC tumor tissue compared to the normal tissue. GDF15, MMP3, AXL, MCSF, I309, and CTACK may be used as biomarkers for OSCC diagnosis and provide a novel study direction for the treatment of OSCC.

Dysregulation of miR-637 serves as a diagnostic biomarker in patients with carotid artery stenosis and predicts the occurrence of the cerebral ischemic event

ABSTRACT The present research aims to explore the relationship between circulating microRNA and carotid artery stenosis (CAS). To evaluate the diagnostic significance of miR-637 in CAS patients and its potential predictive value for cerebral ischemia events through clinical studies. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was used to verify the differences in serum miR-637 between enrolled 97 CAS patients and 90 healthy individuals. Logistic regression analysis of the correlation between the level of miR-637 and the degree of carotid artery stenosis. The receiver operating characteristic (ROC) curve evaluated the diagnostic significance of miR-637 in identifying CAS patients from healthy individuals. Kaplan-Meier survival and Cox regression were used to evaluate the potential predictive ability of serum miR-637 levels during follow-up for cerebral ischemia events. Serum miR-637 of CAS patients was significantly reduced which was a good indicator of severe carotid stenosis (P < 0.001). Reduced miR-637 can identify CAS patients from healthy individuals, demonstrating strong diagnostic capabilities. Furthermore, Kaplan-Meier analysis confirmed that the lower miR-637 levels in CAS, the more cerebral ischemia events (log-rank, P = 0.035), and the Multivariate Cox regressions confirmed that miR-637 was an independent predictor of CAS patients (HR = 0.073, 95%CI = 0.017–0.313, P < 0.001). We confirmed that serum miR-637 in CAS patients was significantly reduced. And reduced miR-637 was not only a potentially reliable biomarker for the diagnosis of CAS but also a useful indicator for predicting future cerebral ischemic events.

Promising biomarkers in patients with advanced coronary artery disease

Background and Aims: Advanced coronary artery disease (CAD) affects in survival time of patients with advance cardiovascular disease. Many biomarkers were proposed for CAD diagnosis and prognosis. Our study was focused to identify the promising diagnostic biomarkers in patients with severe CAD.

Influence of Serum Cholinesterase Levels on Patients Suspected of Having Stable Coronary Artery Disease.

Objective The serum cholinesterase (ChE) level has been used for the evaluation of the nutritional status in daily practice. It has been reported that the serum ChE level is significantly more elevated in patients with three-vessel coronary disease than in normal subjects. Thus, the aim of this study was to assess the influence of serum ChE levels in patients suspected of having stable coronary artery disease (CAD). Methods The relationship between myocardial ischemia and the serum ChE levels was evaluated in 559 consecutive patients suspected of having stable CAD without a history of cardiovascular disease admitted to our hospitals to undergo coronary angiography. Results This study revealed that, in patients suspected of having stable CAD, 1) the frequency of myocardial ischemia was significantly increased in accordance with the serum ChE levels (p<0.001); 2) higher ChE levels were associated with a higher body mass index (p<0.001) and the co-existence of dyslipidemia (p<0.001), including higher values of low-density lipoprotein-cholesterol (p<0.001) and triglycerides (p<0.001) and serum albumin (p<0.001), as well as a younger age (p<0.001); 3) the specificity and sensitivity of myocardial ischemia were 0.599 and 0.658 at the ChE level of 286 IU/L, respectively; and 4) an increased serum ChE (OR=1.66, p<0.001) was an independent risk factor for myocardial ischemia, in patients suspected of having stable CAD. Conclusion The serum ChE level may be an important diagnostic biomarker in patients suspected of having stable CAD.

Assessment of serum synuclein‐γ and squamous cell carcinoma antigen as diagnostic biomarkers in patients with oral squamous cell carcinoma and oral potentially malignant disorders

Clinical diagnosis and monitoring are crucial to reduce the mortality from oral squamous cell carcinoma (OSCC) and oral potentially malignant disorders (OPMDs). It has been demonstrated that synuclein-γ (SNCG) and squamous cell carcinoma antigen (SCCAg) are highly expressed in patients with OSCC and perhaps participate in OSCC progression. This study analyzed the levels of serum SNCG and SCCAg in OSCC, OPMD, and control patients, and evaluated the diagnostic and clinical value of single and combined detection of serum SNCG and SCCAg in OSCC and OPMDs. Serum samples were collected from 197 patients including 87 patients with OSCC, 30 patients with OPMDs, and 80 healthy volunteers as controls. Enzyme-linked immunosorbent assay and statistical analysis were utilized to determine SNCG and SCCAg levels in serum. The levels of SNCG and SCCAg in serum were significantly higher in OSCC compared with OPMDs and controls. There was a correlation between SNCG level and ethnicity, and SCCAg was correlated with differentiation. Furthermore, the area under the curves, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of combined detection of SNCG and SCCAg were better than any single detection. The combined detection of SNCG and SCCAg in serum could become a new standard method to distinguish between OSCC and OPMDs and improve diagnostic performance for OSCC.

SC10 - miR-20a-5p expression as a potential non-invasive diagnostic biomarker in patients with non-obstructive azoospermia

SC10 - miR-20a-5p expression as a potential non-invasive diagnostic biomarker in patients with non-obstructive azoospermia

Gastric Cancer Diagnosis: From Imaging Techniques to Biochemical Biomarkers.

Gastric cancer (GC) has been found to be the second leading cause of cancer-associated deaths in the world, and is usually detected in the advanced stages. It has been shown that surgery is the major therapeutic approach in the treatment of subjects with GC. Hence, early and fast diagnosis of this malignancy is very important for good subject outcomes. Non-invasive diagnostic platforms, including evolutionary endoscopy and positron emission tomography (PET), are employed for the diagnosis of subjects with GC. Along with imaging techniques, the utilization of biomarkers has emerged as a new diagnosis option for early and fast detection of GC. Multiple lines of evidence have revealed a variety of biomarkers, including microRNAs, exosomes, circulating tumor cells, circular RNAs, cell free DNAs, and various proteins, which could be used as diagnostic biomarkers in patients with GC. Taken together, these findings suggest that the joint application of imaging techniques and different biomarkers could be introduced as a new detection approach in the treatment and screening response to therapy in the subjects with GC. Herein, we have summarized various imaging techniques and biomarkers as powerful tools in the detection of GC.

A panel of six-circulating miRNA signature in serum and its potential diagnostic value in colorectal cancer

AimColorectal carcinoma (CRC) is one of the most prevalent cancers throughout the world. Circulating serum-derived microRNAs (miRNAs, miRs) can be used as non-invasive biomarkers for CRC diagnosis. This study aimed to identify a panel of six serum exosomal miRNAs as novel diagnostic biomarkers for CRC. Main methodsExosomes were isolated and characterized from the conditioned media of the human colon adenocarcinoma cells (HCT-116 and Caco2). Sera were isolated from peripheral blood of 45 CRC and also 45 healthy individuals. The expression levels and diagnostic value of candidate circulating miRNAs (miR-19a, miR-20a, miR-150, miR-143, miR-145, and let-7a) were measured through quantitative real-time PCR. Receiver operating characteristic (ROC) curves were applied to evaluate the diagnostic accuracy of selected miRNAs. The association of candidate miRNAs and clinicopathological characteristics e.g. tumor node metastasis (TNM) staging and lymph node metastasis (LNM) were further evaluated. Key findingsCirculating serum miR-19a, miR-20a, miR-150, and let-7a were significantly up-regulated in CRC patients, while miR-143 and miR-145 showed a significant down-regulation. The higher levels of miR-143 and miR-145 in patients with TNM stage I-II were detected, whereas miR-19a, miR-20a, miR-150, and let-7a were highly expressed in TNM stage III. The expression levels of miR-19a, miR-20a, and miR-150 were positively correlated with LNM status, while the expression levels of miR-143 and miR-145 were lower in patients with LNM. Area under the ROC curves of miR-19a, miR-20a, miR-150, miR-143, miR-145, and let-7a were 0.87, 0.83, 0.75, 0.76, 0.78 and 0.71, respectively. SignificanceWe established a panel of six-circulating miRNA signature (i.e. miR-19a, miR-20a, miR-143, miR-145, miR-150, and let-7a) in serum as a non-invasive biomarker for CRC diagnosis. These findings confirm that serum-derived miRNAs have a strong potential to be a diagnostic biomarker for patients with CRC.

Evaluation of Galectin-3 as a Novel Diagnostic Biomarker in Patients with Heart Failure with Preserved Ejection Fraction.

Background Heart failure is a complex cardiovascular disease with a variety of etiologies and heterogeneity. The N-terminal pro-B-type natriuretic peptide (NT-proBNP) value has limited usefulness in diagnosing heart failure with preserved ejection fraction (HFpEF). Aim The aim of the present study is to evaluate serum Galectin-3 as a diagnostic biomarker in patients with HFpEF and to compare Galectin-3 with NT-proBNP levels. Materials and Methods A cross-sectional case–control study including 63 cases of heart failure with ejection fraction ≥50% confirmed by echocardiography. NT-proBNP levels in serum were measured by electrochemiluminescence immunoassay and Galectin-3 levels in serum were measured by using an enzyme-linked-immunosorbent serologic assay kit. Results The median levels of serum Galectin-3 and NT-proBNP in patients were significantly higher than those of controls (26.59 vs. 5.27 and 927 vs. 49.3, p < 0.0001). A positive correlation was observed between serum levels of Galection-3 and NT-ProBNP ( r : 0.21, p = 0.048). At cut-off values of 10.1 ng/mL and 160 pg/mL, serum Galectin-3 has 77.78% sensitivity, 95% specificity with an area under the curve (AUC) of 0.93, and serum NT-proBNP has 71.43% sensitivity, 100% specificity with an AUC of 0.87, respectively, for diagnosing HFpEF. The comparison of receiver operating characteristics curves showed that Galectin-3 has better AUC compared with NT-proBNP in diagnosing HFpEF. Serum Galectin-3 showed a positive correlation with NT-proBNP and lipid parameters. Conclusion Galectin-3 with higher sensitivity and AUC can be used as a valuable biomarker for the diagnosis of HFpEF. Simultaneous testing of both Galectin-3 and NT-proBNP can further improve the detection of patients with HFpEF.

High Level of IL-10 in Cerebrospinal Fluid is Specific for Diagnosis of Primary Central Nervous System Lymphoma.

PurposeThe pathological diagnosis of primary central nervous system lymphoma (PCNSL) by stereotactic brain biopsy and craniotomy is not often applicable due to the high cost and associated complications. In recent years, some biomarkers in cerebrospinal fluid (CSF), including interleukin 10 (IL-10), microRNAs, CXC chemokine ligand 13 (CXCL13), have been reported to be associated with PCNSL. However, this conclusion was controversial. Therefore, this study was to test whether Th17 cell-related cytokines could be used to distinguish PCNSL from other brain tumors.Patients and MethodsTh17 cell-related cytokines in CSF were measured in 108 patients with intracranial tumors, which included 66 PCNSL patients and 42 patients with other types of brain tumors. A receiver-operating characteristic (ROC) curve was utilized to analyze the diagnostic value of the cytokines based on the area under the curve (AUC).ResultsThe CSF IL-10 level and IL-10/IL-6 ratios were significantly higher in PCNSL than in the other brain tumors (58.2 pg/mL VS 1.5 pg/mL, p=0.001; 24.3 VS 0.6, p=0.001). When the cutoff level of IL-10 was set at 8.3 pg/mL, its sensitivity and specificity for diagnosing PCNSL were 59.0% and 98%, respectively. The CSF IL-10 levels over 5pg/mL (+LR 12.3) were of significant value for the diagnosis of PCNSL. These parameters are highly valuable in PCNSL diagnosis, but their sensitivity is less valuable. The sensitivity of IL-4 and IL-17A, the ratio of mature lymphocytes and the monocytes/macrophages ratio in CSF were relatively high. In combination, the sensitivity increased by 15% and the specificity remained above 85%. The best combination was IL-10 and IL-17A, whose sensitivity was 70% and specificity was 96%.ConclusionThe CSF level of IL-10 is a useful diagnostic biomarker in patients with PCNSL. The CSF levels of IL-4, IL-17A, mature lymphocytes and monocytes/macrophages can be used to increase the diagnostic value of CSF IL-10 level and IL-10/IL-6 ratio.

MicroRNA-363-3p serves as a diagnostic biomarker of acute myocardial infarction and regulates vascular endothelial injury by targeting KLF2.

Acute myocardial infarction (AMI) is a serious cardiovascular disease. This study aimed to investigate the diagnostic value of microRNA-363-3p (miR-363-3p) in AMI patients and explore the effects of miR-363-3p on vascular endothelial injury in an AMI rat model. The Expression of miR-363-3p was measured by quantitative real-time PCR. A receiver operating characteristic (ROC) curve was plotted to evaluate the diagnostic value of miR-363-3p in AMI patients. The biomarkers of endothelial injury were estimated using enzyme-linked immunosorbent assays, and the correlation of miR-363-3p with these markers was assessed. AMI rat model was constructed using coronary artery ligation, and the effects of miR-363-3p on endothelial injury and endothelial cell proliferation were analyzed. Serum expression of miR-363-3p was upregulated in the AMI patients compared with healthy controls. The increased serum miR-363-3p serves a candidate diagnostic biomarker of AMI. The correlation analysis indicated that serum miR-363-3p expression was positively correlated with the concentration of endothelial injury biomarkers in AMI patients. Furthermore, the increased endothelial injury biomarkers in AMI rats were all inhibited by the knockdown of miR-363-3p, and the cell proliferation of human umbilical vein endothelial cells was obviously enhanced by the reduction of miR-363-3p. The prediction results shown that Kruppel-like factor 2 (KLF2) is a target of miR-363-3p, and their interaction was proved using a luciferase reporter assay. Collectively, overexpression of miR-363-3p acts as a diagnostic biomarker for patients with AMI, and the downregulation of miR-363-3p improves AMI-associated endothelial injury by targeting KLF2, which indicated that miR-363-3p has a potential to develop the treatment of AMI.

High Serum Levels of Serum 100 Beta Protein, Neuron-specific Enolase, Tau, Active Caspase-3, M30 and M65 in Children with Autism Spectrum Disorders.

ObjectiveThe purpose of this study was therefore to investigate whether neuronal, axonal, and glial cell markers (Neuron-specific enolase [NSE], tau, serum 100 beta protein [S100B], respectively) and apoptosis markers (active caspase 3, M30, M65) and whether these parameters can be used as diagnostic biomarkers in autism spectrum disorders (ASD).MethodsThis study measured the serum S100B, NSE, tau, active caspase 3, M30, and M65 levels in 43 patients with ASD (aged 3−12 years) and in 41 age- and sex-matched healthy controls. ASD severity was rated using the Childhood Autism Rating Scale. The serum levels were determined in the biochemistry laboratory using the ELISA technique. The receiver operator characteristics curve method was employed to evaluate the accuracy of the parameters in diagnosing ASD.ResultsSerum S100B, tau, NSE, active caspase-3, M30, and M65 levels were significantly higher in the patient group than in the control group (p < 0.001, p = 0.002, p = 0.002, p = 0.005, p < 0.001, and p = 0.004, respectively). The cut-off value of S100B was 48.085 pg/ml (sensitivity: 74.4%, specificity: 80.5%, areas under the curve: 0.879, p < 0.001).ConclusionApoptosis increased in children with ASD, and neuronal, axonal, and glial cell injury was observed. In addition, S100B may be an important diagnostic biomarker in patients with ASD. Apoptosis, and neuronal, axonal and astrocyte pathologies may play a significant role in the pathogenesis of ASD, and further studies are now required to confirm this.

Validation of Calprotectin As a Novel Biomarker For The Diagnosis of Pleural Effusion: a Multicentre Trial

Discriminating between malignant pleural effusion (MPE) and benign pleural effusion (BPE) remains difficult. Thus, novel and efficient biomarkers are required for the diagnosis of pleural effusion (PE). The aim of this study was to validate calprotectin as a diagnostic biomarker of PE in clinical settings. A total of 425 patients were recruited, and the pleural fluid samples collected had BPE in 223 cases (53.7%) or MPE in 137 patients (33%). The samples were all analysed following the same previously validated clinical laboratory protocols and methodology. Calprotectin levels ranged from 772.48 to 3,163.8 ng/mL (median: 1,939 ng/mL) in MPE, and 3,216–24,000 ng/mL in BPE (median: 9,209 ng/mL; p < 0.01), with an area under the curve of 0.848 [95% CI: 0.810–0.886]. For a cut-off value of ≤ 6,233.2 ng/mL, we found 96% sensitivity and 60% specificity, with a negative and positive predictive value, and negative and positive likelihood ratios of 96%, 57%, 0.06, and 2.4, respectively. Multivariate analysis showed that low calprotectin levels was a better discriminator of PE than any other variable [OR 28.76 (p < 0.0001)]. Our results confirm that calprotectin is a new and useful diagnostic biomarker in patients with PE of uncertain aetiology which has potential applications in clinical practice because it may be a good complement to cytological methods.

Circulating and tissue microRNAs as a potential diagnostic biomarker in patients with thrombotic events.

Venous and arterial thrombosis are conditions that have a considerable burden if left untreated. The hypoxia-induced by the occluded vessel can disrupt the circulation of any organ, the cornerstone of treating thrombosis is rapid diagnosis and appropriate treatment. Diagnosis of thrombosis may be made by using laboratory tests or imaging techniques in individuals who have clinical manifestations of a thrombotic event. The use of serum micro ribonucleic acids (RNAs) has recently been applied to the diagnosis of thrombosis. These small RNA molecules are emerging as new diagnostic markers but have had very limited applications in vascular disease. Most of the articles provided various microRNAs with different levels of accuracy. However, there remains a lack of an appropriate panel of the most specific microRNA in the literature. The purpose of the present review was to summarize the existing data on the use of microRNAs as a diagnostic biomarker for venous thrombosis.

Uncovering the potential differentially expressed miRNAs as diagnostic biomarkers for hepatocellular carcinoma based on machine learning in The Cancer Genome Atlas database.

The present study aimed to identify novel diagnostic differentially expressed microRNAs (miRNAs/miRs) in order to understand the molecular mechanisms underlying hepatocellular carcinoma. The expression data of miRNA and mRNA were downloaded for differential expression analysis. Optimal diagnostic differentially expressed miRNA biomarkers were identified via a random forest algorithm. Classification models were established to distinguish patients with hepatocellular carcinoma and normal individuals. A regulatory network between optimal diagnostic differentially expressed miRNA and differentially expressed mRNAs was then constructed. The GSE63046 dataset and in vitro experiments were used to validate the expression of the optimal diagnostic differentially expressed miRNAs identified. In addition, diagnostic and prognostic analyses of optimal diagnostic differentially expressed miRNAs were performed. In total, 14 differentially expressed miRNAs (all upregulated) and 2,982 differentially expressed mRNAs (1,989 upregulated and 993 downregulated) were identified. hsa-miR-10b-5p, hsa-miR-10b-3p, hsa-miR-224-5p, hsa-miR-183-5p and hsa-miR-182-5p were considered as the optimal diagnostic biomarkers for hepatocellular carcinoma. The mRNAs targeted by these five miRNAs included secreted frizzled related protein 1 (SFRP1), endothelin receptor type B (EDNRB), nuclear receptor subfamily 4 group A member 3 (NR4A3), four and a half LIM domains 2 (FHL2), NK3 homeobox 1 (NKX3-1), interleukin 6 signal transducer (IL6ST) and forkhead box O1 (FOXO1). ‘Bile acid biosynthesis and cholesterol’ was the most enriched signaling pathways of these target mRNAs. The expression validation of the five miRNAs was consistent with the present bioinformatics analysis. Notably, hsa-miR-10b-5p and hsa-miR-10b-3p had a significant prognosis value for patients with hepatocellular carcinoma. In conclusion, the five differentially expressed miRNAs may be considered as diagnostic biomarkers for patients with hepatocellular carcinoma. In addition, the differential expression levels of the targets of these five mRNAs, including SFRP1, EDNRB, NR4A3, FHL2, NKX3−1, IL6ST and FOXO1, may be involved in hepatocellular carcinoma tumorigenesis.

Exosomal MicroRNAs as Liquid Biopsy Biomarkers in Hepatocellular Carcinoma.

PurposeHepatocellular carcinoma (HCC) has a high incidence in China and exploring effective ways for early diagnosis is an important method to improve the prognosis of patients with HCC. Additional studies reported that. Some kinds of microRNA (miRNA) in plasma will change accordingly during HCC progress, and this change can be used to diagnose HCC, especially with miRNA-122, miRNA-21 and miRNA-96. We were aiming at investigating the values of the exosomal miRNAs in diagnosis and prognosis for HCC patients.Patients and MethodsBlood samples from 50 patients with HCC and 50 patients with hepatic cirrhosis and 50 healthy volunteers were obtained. The diagnostic accuracy of the plasma and exosomal miRNAs and the comparisons among different groups were measured by the area under the curve (AUC) on receiver operating characteristic (ROC) curve analysis.ResultsExpression levels of miRNA-21 and miRNA-96 were significantly higher in patients with HCC and of miRNA-122 were significantly lower in HCC compared with cirrhotic patients in both exosomes and plasma. Among different groups, exosomal miRNA-122, miRNA-21 and miRNA-96 were significantly more accurate in diagnosing HCC than those miRNAs in plasma and the alpha-fetoprotein (AFP) level. The miRNA panel had high accuracy in discriminating HCC from the cirrhosis group (AUC 0.924; 95% CI; sensitivity 82%, specificity 92%) and healthy volunteers’ group. Exosomal miRNA-21 and miRNA-96 with low expression and miRNA-122 with high expression could be associated with a patient’s survival time. However, the miRNA panel could better predict the HCC patient’s survival time compared with each miRNA individually.ConclusionThis study showed that the expression levels of miRNA-122, miRNA-21 and miRNA-96 in exosomes were more significantly changed than those miRNAs in plasma in patients with HCC compared with cirrhotic patients, and the exosomal miRNA panel containing miRNA-122, miRNA-21 and miRNA-96 could be defined as a diagnostic biomarker for patients with HCC. We also conclude that different expression of exosomal miRNAs, especially the miRNA panel, could predict the HCC patient’s prognosis.