Circulating miRNA-29b and Sclerostin Levels Correlate with Coronary Artery Calcification and Cardiovascular Events in Maintenance Hemodialysis Patients

Objective. Coronary artery calcification (CAC) is a common complication in end-stage renal disease (ESRD) patients undergoing maintenance hemodialysis (MHD), and the extent of CAC is a predominant predictor of cardiovascular outcomes in MHD patients. In this study, we sought to uncover the relationship between circulating miRNA-29b, sclerostin levels, CAC, and cardiovascular events (CVEs) in MHD patients. Methods. This study recruited patients receiving MHD for at least three months in the Hainan General Hospital between January 2016 and June 2019, and all patients were followed up 24 months for CVEs. The serum level of sclerostin was determined by enzyme-linked immunosorbent assay (ELISA) and miRNA-29b expression by real-time qPCR (RT-qPCR). All patients received cardiac CT scans to evaluate CAC, and CAC scores were expressed in Agatston units. The MHD patients with CACs <100 were arranged into the CAC (<100) group, those with 100–400 CACs into the CAC (100–400) group, and those with CACs >400 into the CAC (>400) group. Net reclassification index (NRI) and integrated discrimination index (IDI) were calculated to assess the predictive performance of serum sclerostin level for the occurrence of CVEs. Results. Compared with the CAC (<100) group, the CAC (>400) group had higher proportions of older patients, hypertension and diabetes mellitus patients, longer dialysis duration, higher mean arterial pressure (MAP), higher levels of high-sensitivity C-reactive protein (hs-CRP), alkaline phosphatase (ALP), and phosphate ( P < 0.05 ). It was found that the CAC (100–400) and CAC (>400) groups exhibited higher serum levels of sclerostin but lower levels of miRNA-29b than the CAC (<100) group ( P < 0.05 ) and the CAC (>400) group had a higher level of sclerostin and a lower level of miRNA-29b than the CAC (100–400) group ( P < 0.05 ). The circulating level of miRNA-29b was negatively correlated with the serum level of sclerostin in MHD patients (r = −0.329, P < 0.01 ). The multivariate logistic regression analysis showed that hs-CRP, phosphate, sclerostin, and miRNA-29b were independent risk factors for CAC in MHD patients ( P < 0.05 , Table 2). ROC for prediction of CAC by sclerostin yielded 0.773 AUC with 95% CI 0.683–0.864 ( P < 0.01 ). As depicted by Kaplan–Meier curves of CVE incidence in MHD patients according to median sclerostin (491.88 pg/mL) and median miRNA-29b (Ct = 25.15), we found that serum levels of sclerostin and miRNA-29b were correlated with the incidence of CVEs in MHD patients. When a new model was used to predict the incidence of CVEs, NRI 95% CI was 0.60 (0.16–1.03) ( P < 0.05 ) and IDI 95% CI was 0.002 (−0.014 to 0.025) ( P < 0.05 ), suggesting that sclerostin added into the old model could improve the prediction of the incidence of CVEs. Conclusions. These data suggest that circulating miRNA-29b and sclerostin levels are correlated with CAC and incidence of CVEs in MHD patients. Higher sclerostin and lower miRNA-29b may serve as independent risk factors for the incidence of CVEs in MHD patients.

Serum MicroRNA-222 Expression for Malignancy Prediction in Euthyroid Patients with Indeterminate Thyroid Nodule

Background The Prevalence of thyroid nodules is rising nowadays, luckily most of them are benign. The risk of malignancy 5-15%, which necessitates the ultimate need to accurately distinguish benign from malignant nodule to avoid unnecessary thyroidectomy with risk of recurrent laryngeal nerve injury, postoperative hypothyroidism and lifetime thyroid replacement therapy, and other complications related to surgery and anaesthesia. Recent evidence suggests that circulating miRNA might have probable advantage as diagnostic or prognostic markers for numerous cancers. Given their reproducible and constant presence in sera, miRNA profiles have emerged as a non-invasive method to categorise a wide variety of human cancers. Aim of the study To evaluate a possible relationship between the expression level of circulating miRNA-222 and the histological outcome of euthyroid patients undergoing thyroidectomy for thyroid nodules with indeterminate FNAB cytology. Patients and Methods 45 patients of both genders, of age ranging from 19-70 years old visiting endocrine clinic or admitted to the endocrine surgical department with indeterminate thyroid nodules planned for thyroidectomy were included. All pateints were subjected to full medical history taking, general and local clinical examination, laboratory investigations (thyroid function tests), quantitative assay of serum micro RNA-222 expression by quantitative Real-Time polymerase chain reaction (qRT-PCR), ultrasonography imaging of thyroid gland, fine needle aspiration biopsy and cytology of the thyroid nodule, histopathological examination after thyroidectomy. Results The incidence of thyroid nodules was predominant in female gender in benign group and malignant group. Risk of malignancy increases as TI-RADS and Bethesda scores increases. Also, larger nodule in size has a more risk of malignancy (p = 0.034). Expression level of circulating miRNA222 in serum can’t differentiate between healthy, benign and malignant patients where there was no significant difference between them statistically (p = 0.867). Circulating miRNA-222 is a poor predicator for malignant nodules with sensitivity of 50%, specificity of 32.43%, with high negative predictive value (NPV=75%). Conclusion Expression level of circulating miRNA-222 is a poor predictor of malignant nodules in our studied group. The larger the nodule size the more risk of malignancy. Also, as TI-RADS and Bethesda scores increases the more risk of malignancy.

Integrated miRNA/cytokine/chemokine profiling reveals immunopathological step changes associated with COVID-19 severity

Circulating microRNAs (miRNAs) are exceptional mechanism-based correlates of disease, yet their potential remains largely untapped in COVID-19. Here, we determined circulating miRNA and cytokine and chemokine (CC) profiles in 171 blood plasma samples from 58 hospitalised COVID-19 patients. Thirty-two miRNAs were differentially expressed in severe cases when compared to moderate and mild cases. These miRNAs and their predicted targets reflected key COVID-19 features including cell death and hypoxia. Compared to mild cases, moderate and severe cases were characterised by a global decrease in circulating miRNA levels. Partial least squares regression using miRNA and CC measurements allowed for discrimination of severe cases with greater accuracy (87%) than using miRNA or CC levels alone. Correlation analysis revealed severity group-specific associations between CC and miRNA levels. Importantly, the miRNAs that correlated with IL6 and CXCL10, two cardinal COVID-19-associated cytokines, were distinct between severity groups, providing a novel qualitative way to stratify patients with similar levels of proinflammatory cytokines but different disease severity. Integration of miRNA and CC levels with clinical parameters revealed severity-specific signatures associated with clinical hallmarks of COVID-19. Our study highlights the existence of severity-specific circulating CC/miRNA networks, providing insight into COVID-19 pathogenesis and a novel approach for monitoring COVID-19 progression.

Blood Circulating miRNA Pairs as a Robust Signature for Early Detection of Esophageal Cancer

Esophageal cancer (EC) is a common malignant tumor in the digestive system which is often diagnosed at the middle and late stages. Noninvasive diagnosis using circulating miRNA as biomarkers enables accurate detection of early-stage EC to reduce mortality. We built a diagnostic signature consisting of four miRNA pairs for the early detection of EC using individualized Pairwise Analysis of Gene Expression (iPAGE). Profiling of miRNA expression identified 496 miRNA pairs with significant relative expression change. Four miRNA pairs consistently selected from LASSO were used to construct the final diagnostic model. The performance of the signature was validated using two independent datasets, yielding both AUCs and PRCs over 0.99. Furthermore, precision, recall, and F-score were also evaluated for clinical application, when a fixed threshold is given, resulting in all the scores are larger than 0.92 in the training set, test set, and two validation sets. Our results suggested that the 4-miRNA signature is a new biomarker for the early diagnosis of patients with EC. The clinical use of this signature would have improved the detection of EC for earlier therapy and more favorite prognosis.