Serum miR-21 Research Articles

Serum bta-miRNA-375 as a potential biomarker for the early diagnosis of enzootic bovine leukosis.

To identify a biomarker for the early diagnosis of enzootic bovine leukosis (EBL) caused by bovine leukemia virus (BLV), we investigated the expression of a microRNA, bta-miR-375, in cattle serum. Using quantitative reverse-transcriptase PCR analysis, we measured bta-miR-375 levels in 27 samples from cattle with EBL (EBL cattle), 45 samples from animals infected with BLV but showing no clinical signs (NS cattle), and 30 samples from cattle uninfected with BLV (BLV negative cattle). In this study, we also compared the kinetics of bta-miR-375 with those of the conventional biomarkers of proviral load (PVL), lactate dehydrogenase (LDH), and thymidine kinase (TK) from the no-clinical-sign phase until EBL onset in three BLV-infected Japanese black (JB) cattle. Bta-miR-375 expression was higher in NS cattle than in BLV negative cattle (P < 0.05) and greater in EBL cattle than in BLV negative and NS cattle (P < 0.0001 for both comparisons). Receiver operating characteristic curves demonstrated that bta-miR-375 levels distinguished EBL cattle from NS cattle with high sensitivity and specificity. In NS cattle, bta-miR-375 expression was increased as early as at 2 months before EBL onset-earlier than the expression of PVL, TK, or LDH isoenzymes 2 and 3. These results suggest that serum miR-375 is a promising biomarker for the early diagnosis of EBL.

Correlation analysis of serum miR-145 and miR-210 with carotid artery stenosis and their predictive value for cerebral ischemic events

Objective To analyze the significance of serum miR-145 and miR-210 expression levels in the diagnosis of carotid artery stenosis. Methods During the same period, 55 healthy individuals who received physical examination in the same hospital were recruited as controls and assigned to a non-stenosis group. Among the included patients, there were 45 cases of mild stenosis, 14 cases of moderate stenosis, and 6 cases of severe stenosis after carotid color Doppler ultrasonography. The expression levels of miR-145 and miR-210 in serum were measured using real-time fluorescence quantitative polymerase chain reaction (qPCR) technology. Results The expression levels of serum miR-145 and miR-210 in carotid artery stenosis group were significantly lower than those in non-stenosis group (p < 0.001). Multivariate Logistic regression analysis showed that smoking history, diabetes, hypertension and total cholesterol were positively correlated with the occurrence of carotid artery stenosis (p < 0.05). The expression levels of miR-145 and miR-210 were significantly negatively correlated with carotid artery stenosis (p < 0.001). In addition, patients with carotid artery stenosis and low expression levels of miR-145 and miR-210 had a greater risk of cerebral ischemia (p < 0.05). Cox regression analysis showed that the low expression of miR-145 and miR-210 were independent predictors of cerebral ischemic events. ROC analysis confirmed that miR-145 and miR-210 had good diagnostic efficacy in cerebral ischemia (p < 0.001). Conclusion The decreased expression of miR-145 and miR-210 in serum is closely related to the diagnostic significance of carotid artery stenosis, and may be used to predict the occurrence of cerebral ischemic events.

Serum miR-16 and CA15.3 combination as early diagnostic biomarkers for breast cancer in Egyptian females

Serum miR-16 and CA15.3 combination as early diagnostic biomarkers for breast cancer in Egyptian females

Downregulation of Serum miR-133b and miR-206 Associate with Clinical Outcomes of Progression as Monitoring Biomarkers for Metastasis Colorectal Cancer Patients.

Colorectal cancer (CRC) is the third most common cancer in the world. Noncoding RNAs or microRNAs (miRNAs; miRs) biomarkers can play a role in cancer carcinogenesis and progression. Specific KRAS and EGFR mutation are associated with CRC development playing a role in controlling the cellular process as epigenetic events. Circulating serum miRs can serve for early diagnosis, monitoring, and prognosis of CRC as biomarkers but it is still unclear, clinically. To determine potential biomarkers of circulating serum miR-133b and miR-206 in CRC patients Methods: Bioinformatic prediction of microRNA was screened followed by TargetScanHuman7.2, miRTar2GO, miRDB, MiRanda, and DIANA-microT-CDS. Forty-four CRC serum (19 locally advanced, 23 distant advanced CRC) and 12 normal serum samples were subsequently extracted for RNA isolation, cDNA synthesis, and miR validation. The candidate circulating serum miR-133b and miR-206 were validated resulting in a relative expression via quantitative RT-PCR. Relative expression was normalized to the spike-internal control and compared to normal samples as 1 using the -2ΔΔCt method in principle. Our results represented 9 miRs of miR-206, miR-155-5p, miR-143-3p, miR-193a-3p, miR-30a- 5p, miR-30d-5p, miR-30e-5p, miR-543, miR-877-5p relate to KRAS-specific miRs, whereas, 9 miRs of miR-133b, miR-302a-3p, miR-302b-3p, miR-302d-3p, miR-302e, miR-520a-3p, miR-520b, miR-520c- 3p and miR-7-5p relevance to EGFR-specific miRs by using the bioinformatic prediction tools. Our results showed a decreased expression level of circulating serum miR-133b as well as miR-206 associating with CRC patients (local and advanced metastasis) when compared to normal (P < 0.05), significantly. The circulating serum miR-133b and miR-206 can serve as significant biomarkers for monitoring the clinical outcome of progression with metastatic CRC patients. Increased drug-responsive CRC patients associated with crucial molecular intervention should be further explored, clinically.

Clinical Significance of Serum miR-21, CA153 and CEA in Breast Cancer

Clinical Significance of Serum miR-21, CA153 and CEA in Breast Cancer

The expression of miR-21, HSP90a and gGASP-1 in serum of patients with lung cancer and their correlation with pathological subtypes.

To investigate the expression of miR-21, heat shock protein-90a (HSP90a) and G protein-coupled receptorrelated sorting protein 1(GASP-1) in the serum of lung cancer patients and their correlation with pathological subtypes. Eighty patients with lung cancer were included in the lung cancer group from May 2020 to May 2022, and 40 volunteers who underwent physical examination were randomly included in the control group according to the group ratio of 2:1. This ratio balances the need for a sufficiently large experimental group to detect significant effects with the practicality of recruiting a manageable control group. To ensure the validity of our findings, we meticulously calculated the sample size to achieve adequate statistical power, thus enabling us to draw reliable conclusions. Serum miR-21, HSP90a and GASP-1 levels of patients in the two groups were detected. We quantitatively assessed the serum levels of miR-21, HSP90a, and GASP1 in lung cancer patients and healthy volunteers. We employed enzyme-linked immunosorbent assay (ELISA) for HSP90a and GASP-1, and reverse transcription-polymerase chain reaction (RT-PCR) for miR-21, ensuring precise quantification. To explore the correlation between it and pathological subtypes, TNM stage and lymph node metastasis of lung cancer patients. TNM stands for Tumor, Node, and Metastasis. This system is widely used for staging cancer and describes the size and extent of the primary tumor (T), the absence or presence of cancer in nearby lymph nodes (N), and whether the cancer has spread to other parts of the body (M). The serum levels of miR-21, HSP90a and GASP1 in lung cancer group were higher than those in control group (P < 0.05). ROC curve analysis showed that serum miR-21, HSP90a and GASP-1 levels had certain value in the diagnosis of lung cancer, and their AUC values were 0.901, 0.874 and 0.865, respectively (P < 0.05). There was no difference in the relative expression level of serum miR-21 between squamous cell carcinoma group and adenocarcinoma group (P>0.05), but the levels of HSP90a and GASP-1 in adenocarcinoma group were higher than those in squamous cell carcinoma group (P < 0.05). There was no difference in the levels of serum miR-21, HSP90a and GASP-1 between stage I and stage II groups (P>0.05). The levels of serum miR-21, HSP90a and GASP-1 in stage III and stage IV groups were higher than those in stage I and stage II groups, and those in stage IV were higher than those in stage III group (P < 0.05). The serum levels of miR-21, HSP90a and GASP-1 in patients with metastasis were higher than those in patients without metastasis (P < 0.05). Our study concludes that there is a notable association between elevated serum levels of miR-21, HSP90a, and GASP-1 and lung cancer. However, it is crucial to acknowledge that these findings are preliminary and further statistical analysis is needed to strengthen these associations. Future studies with comprehensive statistical evaluation will be vital to validate these potential biomarkers for lung cancer diagnosis and prognosis.

Evaluation of ankle brachial index, serum miR-103 and LP-PLA2 in the prognosis of acute ischemic stroke.

To explore the prognostic value of ankle brachial index (ABI), serum microribonucleic acid-103 (miR-103), and lipoprotein associated phospholipase A2 (LP-PLA2) indicators in patients with acute ischemic stroke (AIS). A retrospective analysis was conducted using the medical records of 202 patients with AIS admitted to the First Affiliated Hospital of Hebei North University from June 2019 to December 2022. Patients were divided into two groups based on their prognosis: the Poor-group (n=72) and the Good-group (n=130). Levels of ABI, serum miR-103, and LP-PLA2 indicators were compared between the two groups. Multivariate logistic regression analysis was used to analyze the independent risk factors for the poor prognosis in patients with AIS, and the receiver operating characteristic (ROC) curve was used to evaluate the predictive ability of ABI, serum miR-103, and LP-PLA2 levels on the prognosis of AIS. Seventy two patients had a poor prognosis (35.6%) and 130 had a good prognosis (64.4%). The Poor-group had a higher proportion of elderly patients, patients with a history of diabetes and hypertension, abnormal ABI, and elevations in serum miR-103 and LP-PLA2 compared to the Good-group (P<0.05). Multivariate logistic regression analysis showed that abnormal ABI, and high levels of serum miR-103 and LP-PLA2 were independent risk factors for the poor prognosis. ROC curve provided a combined AUC of 0.862, which was higher than that of the individual ABI, serum miR-103, and LP-PLA2 curves, with values of 0.625, 0.749, and 0.696, respectively (P<0.05). Abnormal ABI, and high serum miR-103 and LP-PLA2 levels are independent risk factors for poor prognosis in AIS patients. They can be used as important indicators for predicting the prognosis of AIS.

A novel β-cyclodextrin-assisted enhancement strategy for portable and sensitive detection of miR-21 in human serum.

Benefiting from our discovery that β-cyclodextrin (β-CD) could enhance the catalytic activity of invertase through hydrogen bonding to improve detection sensitivity, a highly sensitive and convenient biosensor for the detection of miR-21 was proposed, which is based on the simplicity of reading signals from a personal glucose meter (PGM), combined with self-assembled signal amplification probes and the performance of β-CD as an enhancer. In the presence of miR-21, magnetic nanoparticle coupled capture DNA (MNPs-cDNA) could capture it and then connect assist DNA/H1-invertase (aDNA/H1) and self-assembled signal amplification probes (H1/H2) in turn. As a result, a "super sandwich" structure was formed. The invertase on MNPs-cDNA could catalyze the hydrolysis of sucrose to glucose and this catalytic process could be enhanced by β-CD. The PGM signal exhibited a linear correlation with miR-21 concentration within the range of 25 pmol L-1 to 3 nmol L-1, and the detection limit was as low as 5 pmol L-1 with high specificity. Moreover, the recoveries were 103.82-124.65% and RSD was 2.59-6.43%. Furthermore, the biosensor was validated for the detection of miR-21 in serum, and the results showed that miR-21 levels in serum samples from patients with Diffuse Large B-Cell Lymphoma (DLBCL) (n = 12) were significantly higher than those from healthy controls (n = 12) (P < 0.001). Therefore, the ingenious combination of PGM-based signal reading, self-assembled signal amplification probes and β-CD as an enhancer successfully constructed a convenient, sensitive and specific biosensing method, which is expected to be applied to clinical diagnosis.

Variation and significance of serum microRNA-21 level in pediatric pulmonary artery hypertension associated with congenital heart disease.

This study strives to the variation and significance of microRNA-21 (miR-21) in children with congenital heart disease (CHD)-related pulmonary artery hypertension (PAH). Children with CHD (n = 179) were selected as subjects, including 101 children without PAH and 78 children with PAH. All children underwent general data collection, laboratory examination, echocardiography and cardiac catheterization. After detection of serum miR-21 expression, the predictive value and the impacts of serum miR-21 for PAH and postoperative critical illness were analyzed. Serum creatine kinase isoenzyme (CK-MB), B-type natriuretic peptide (BNP) and miR-21 were elevated, but ejection fraction (EF) and cardiac index (CI) were decreased in the CHD-PAH group. Serum miR-21 assisted in predicting PAH in CHD children, with the area under curve (AUC) of 0.801 (95% CI of 0.735∼0.857), a cut-off value of 2.56, sensitivity of 73.08, and specificity of 72.28%. Serum miR-21 in children with CHD-PAH was correlated with clinicopathological indicators such as systolic pulmonary artery pressure, mean pulmonary arterial pressure, BNP and CI. Serum miR-21 helped predict the development of postoperative critical illness in children with CHD-PAH, with an AUC of 0.859 (95% CI: 0.762-0.927, cut-off value: 4.55, sensitivity: 69.57%, specificity: 92.73%). Increased serum miR-21 was an independent risk factor of postoperative critical illness in children with CHD-PAH. Serum miR-21 was upregulated in children with CHD-PAH, which may serve as a predictive biomarker for the onset of PAH and postoperative critical illness in CHD children.

Dysregulation of miR-122, miR-574 and miR-375 in Egyptian patients with breast cancer.

The early detection of breast cancer (BC) is receiving global attention, creating an urgent need for more sensitive and comprehensive strategies for preventive intervention, therapy assessment, and prognosis prediction. Aberrant expression of miRNAs has been observed in various malignancies and may be potential targets for therapy. Our study aims to examine the expression profiles of miR-375, miR-574-3p, and miR-122 in the sera of Egyptian women with BC, benign breast lesions, and a control group. We hope to determine if these miRNAs can serve as minimally invasive biomarkers for BC. This is a case-control study in which 77 patients with newly diagnosed BC, 20 patients with benign breast tumors, and 30 normal healthy subjects as controls were recruited from the outpatient clinic of the National Cancer Institute. The assessment of miRNAs was conducted using RT-PCR (Applied Biosystems). The expression level of miRNA-122 was significantly upregulated in the BC group, while the expression levels of miRNA-574 and miRNA-375 showed significant downregulation in BC patients. Serum miR-122 and miRNA-375 were able to distinguish breast cancer from the benign and control groups in ROC curve analysis, with AUCs of 0.786 and 0.796, respectively. Our results also showed that serum miR-122 and miR-574 are significant predictor variables in the multivariate analysis, after adjusting for age. Our findings suggest that miR-122 may act as an onco-microRNA, while miR-574 and miR-375 may have a main tumour suppressor role. The studied miRNAs may serve as minimally invasive biomarkers for cases of breast cancer and as promising potential therapeutic targets for breast cancer.

Comparison of Mir122 expression in children with biliary atresia and healthy group.

Biliary atresia (BA) is the primary cause of neonatal jaundice with various pathological mechanisms. Many BA patients may experience progressive liver dysfunction and eventually need a liver transplant. Therefore, identifying potential non-invasive biomarkers for BA is crucial. miR-122, the most abundant microRNA in the liver, plays significant roles in different liver diseases. This study aimed to assess miR-122 levels in BA patients. Eighteen patients with biliary atresia were selected at random from the Shiraz Pediatric Liver Cirrhosis Cohort Study (SPLCCS), along with 18 healthy controls. Blood samples were collected, and biochemical parameters (such as liver function tests) were measured. Quantitative reverse-transcription PCR (RT-PCR) was conducted on serum samples from both the case and control groups to analyze miR-122 levels. The study results indicated that serum miR-122 expression in BA patients was elevated compared to the control group, although it did not reach statistical significance. Additionally, no correlation was found between miR-122 expression and serum levels of liver enzymes or other laboratory findings in BA cases. miR-122 could be a potential target for diagnosing BA; however, further research with a larger population is necessary to determine if miR-122 could serve as a useful biomarker for diagnosing BA.

Pre and Postoperative Serum miR-21 Expression Levels in Oral Cancer and it’s Association with Clinical and Histological Parameters: An Observational Study

Introduction: The patterns of microRNA (miRNA) expression have opened up new avenues in the search for prognostic biomarkers and potential therapeutic targets for various tumours. In oral carcinogenesis research, analysing microRNAs expressed in Oral Squamous Cell Carcinoma (OSCC) unveils a complex network of interest. miR-21 is known to be overexpressed in numerous solid tumours and is linked to the progression of malignancies in hepatocellular carcinomas, breast cancer, and colon carcinomas. Aim: To determine the impact of surgical excision on serum miR-21 expression levels in OSCC cases and to establish correlations with clinicopathological parameters. Materials and Methods: The study was an exploratory prospective observational study conducted with proper institutional ethical approval at the Cancer Research Institute (CRI), Himalayan Institute of Medical Sciences (HIMS), Jolly Grant, Dehradun, Uttarakhand, India. Fifty-six histologically confirmed OSCC cases were enrolled along with 25 healthy subjects as controls from May 2021 to June 2023. The relative fold expression change was calculated using the Livak method (2-∆∆ct). Data analysis was performed using software such as Statistical Package for Social Sciences (SPSS) version 20.0 and MS Excel. Non parametric statistical tests such as Wilcoxon signed-rank test, MannWhitney test, and Kruskal-Wallis test were utilised. Results: Out of 56 sample included, 28 exhibited high expression of miR-21 (p-value&lt;0.001), while 27 cases showed downregulation postsurgery (p-value&lt;0.001), with one sample showing the same level of expression. In cases where the time difference between pre and postsurgery samples was over 25 days, no significant change was observed (p-value=0.06), and similarly, in cases with a time difference below 25 days, no significant difference was noted (p-value=0.14). A significant negative correlation was found between presurgery serum Albumin to Globulin ratio (A:G ratio) and miR-21 expression (p-value &lt;0.05), while no other parameters showed a significant correlation with miR-21. Conclusion: miR-21 expression decreased significantly in some OSCC cases; however, in the majority of cases, it increased postsurgery. A significant correlation was observed between miR-21 expression and the serum A:G ratio.

Clinical Significance of Serum miR-21, CA153 and CEA in Breast Cancer

Clinical Significance of Serum miR-21, CA153 and CEA in Breast Cancer

Correlation between serum microRNA-122 and VEGF expression and pregnancy outcome in gestational diabetes mellitus patients.

Gestational diabetes mellitus (GDM) seriously influences the health of mothers and babies, and there are still no effective early diagnostic markers. Therefore, our study planned to probe the correlation between serum microRNA-122 and VEGF expression and pregnancy outcome in GDM patients. This was a retrospective study of the correlation between serum microRNA-122 and vascular endothelial growth factor (VEGF) expression and pregnancy outcome in GDM patients. Sixty GDM patients admitted to the Fourth Hospital of Shijiazhuang from January 2021 to October 2022 were included in the research group (RG), and another 60 healthy pregnant women were included in the control group (CG). Serum miR-122 and VEGF levels were quantified using quantitative real-time polymerase chain reaction. The value of miR-122 and VEGF in predicting adverse pregnancy outcomes was analyzed by receiver operating characteristic curve. Serum miR-122 and VEGF levels in the RG were higher relative to the CG. The total occurrence of adverse pregnancy outcomes in the RG was higher relative to the CG (P<0.05). Serum miR-122 together with VEGF levels in the poor outcome group was higher relative to the good outcome group (P<0.05). ROC analysis revealed that miR-122 and VEGF could be used to predict adverse pregnancy outcome (P<0.0001). The area under the curve of miR-122 was 0.860, 95% confidence interval (CI) =0.793-0.926, and the area under the curve of VEGF was 0.780, 95% CI =0.694-0.866. Serum levels of miR-122, VEGF were positively related with abortion, preterm delivery, low birth weight infants, macrogenesis infants, and fetal development abnormalities (P<0.001). The higher serum miR-122 and VEGF levels in GDM patients with satisfactory blood glucose control, the greater the probability of adverse pregnancy outcome, which should be paid attention to by clinicians.

Fecal miR-223 is a noninvasive biomarker for estimating Crohn's disease activity.

MicroRNA-223 (miR-223) has emerged as a promising noninvasive biomarker for Crohn's disease (CD). However, it is unclear which tissue derived miRNA-223 can more accurately estimate CD disease activity. To collect serum, terminal ileal mucosa biopsy and fecal samples from CD patients and healthy controls. The CD Activity Index (CDAI) score, Montreal classification, maintenance medicines, peripheral blood inflammatory markers, fecal calprotectin (FC) and the Simple Endoscopic Score for CD (SES-CD) were recorded. To compare the expression of miR-223 in the serum, intestinal tissue, and feces. MiR-223 expression levels in the serum, intestinal tissue and feces of CD patients were significantly higher than those of controls. The level of miR-223 in the serum, intestinal tissue and feces increased significantly in active CD patients compared with that in inactive CD patients. The levels of serum, intestinal tissue and fecal miR-223 were correlated with the CDAI. Serum miR-223 was also correlated with C-reactive protein (CRP) and IL-6, tissue miR-223 correlated with IL-6 and FC, and fecal miR-223 correlated with FC. In terms of the association with FC, fecal miR-223 had a higher Spearman r value than tissue miR-223. The area under the curve (AUC) values of serum, tissue and fecal miR-223 to diagnose CD were similar to those of CRP and FC (AUC > 0.8). The AUC values of tissue and fecal miR-223 to evaluate CD disease activity were 0.832 and 0.818, respectively, and were higher than serum miR-223, CRP and FC. Fecal miR-223 had a higher specificity of 92.3%. Fecal miR-223 might be a novel, noninvasive biomarker for estimating the disease activity of CD patients.

A Comparative Analysis of MicroRNA Expression in Mild, Moderate, and Severe COVID-19: Insights from Urine, Serum, and Nasopharyngeal Samples.

COVID-19, caused by the SARS-CoV-2 virus, manifests with a wide range of clinical symptoms that vary from mild respiratory issues to severe respiratory distress. To effectively manage and predict the outcomes of the disease, it is important to understand the molecular mechanisms underlying its severity. This study focuses on analyzing and comparing the expression patterns of microRNAs (miRNAs) in serum, urine, and nasopharyngeal samples from patients with mild, moderate, and severe COVID-19. The aim is to identify potential associations with disease progression and discover suitable markers for diagnosis and prognosis. Our findings indicate the consistent upregulation of miR-21, miR-146a, and miR-155 in urine, serum, and nasopharyngeal samples from patients with mild COVID-19. In moderate cases, there were more significant changes in miRNA expression compared to mild cases. Specifically, miR-let-7 demonstrated upregulation, while miR-146b exhibited downregulation. The most notable alterations in miRNA expression profiles were observed in severe COVID-19 cases, with a significant upregulation of miR-223. Moreover, our analysis using Receiver-operating characteristic (ROC) curves demonstrated that miR-155, miR-let-7, and miR-223 exhibited high sensitivity and specificity, suggesting their potential as biomarkers for distinguishing COVID-19 patients from healthy individuals. Overall, this comparative analysis revealed distinct patterns in miRNA expression. The overlapping expression patterns of miRNAs in urine, serum, and nasopharyngeal samples suggest their potential utility in discriminating disease status.

Clinical significance of serum miR-21, CA153 and CEA in breast cancer

Clinical significance of serum miR-21, CA153 and CEA in breast cancer

Correlation of the novel biomarker cellular communication network factor 1 (CCN1) with miR-155 in serum of patients with dilated cardiomyopathy

Abstract Background We recently reported an independent prognostic ability of serum CCN1 to predict all-cause mortality in DCM, irrespective of its aetiology (inflammatory DCM (DCMi) or conventional DCM). Interestingly, CCN1 levels were lower in patients with DCMi than in patients with conventional DCM. In a murine model, miR-155, which has key functions in inflammation, repressed the expression of CCN1 and impeded its function in angiogenesis. In a recent study, patients with DCMi had higher miR-155 plasma levels than those with conventional DCM. Purpose The present study evaluated whether circulating levels of CCN1 and miR-155 are associated in order to provide insight into the underlying pathophysiology. Methods Patients with a primary diagnosis of DCM, defined as LVEF &amp;lt;45% and an increased LVEDD (according to HENRY &amp;gt;117%), were included in this single-centre study. Exclusion criteria comprised primary valvular diseases (≥ second degree), acute myocarditis, active infectious diseases, pulmonary diseases, cancer, chronic alcoholism, and heart failure of other origins. CCN1 levels were determined in serum at study inclusion using an enzyme-linked immunosorbent assay. miR-155-5p was measured in serum using quantitative real-time PCR and normalized to a spike-in of miR-39-3p from C. elegans for analysis. The primary endpoint was all-cause mortality during follow-up. An adjusted multivariable Cox regression model (comprising age, sex, time of symptoms, LVEF, eGFR, CRP, and NT-proBNP) was used to assess the association between CCN1 or miR-155 with all-cause mortality. Results Among 283 patients in the DCM cohort with CCN1 data, miR-155 measurements were available for analysis in 270 patients. Among those, 77.4% were males at a median age of 55.3 [IQR 47.8, 64.7] years with 3.84 [IQR 1.1, 19.3] months since onset of disease who had severely reduced LVEF (31 [IQR 26, 37] %), elevated LVEDD (67 [IQR 62, 72] mm), and normal eGFR (CKD-EPI) (91.5 [IQR 74.01, 103.3] ml/min). During a median follow-up of 12.4 [IQR 10.5, 13.9] years, a total of 101 (37.4%) patients died. There was no significant difference in miR-155 levels between DCMi and conventional DCM (ΔCt: 14.84 vs 14.94, P = 0.60; and ΔΔCt values 1.68 vs 1.49, P = 0.42). A positive correlation was found for miR-155 (relative expression ΔΔCt values) with CCN1 in serum from patients with conventional DCM (rS = 0.251, p = 0.002) but not with DCMi (rS = 0.007, p = 0.94) (Figure 1). Unlike CCN1 (HR 1.11; 95% CI 1.04, 1.19; p = 0.002), miR-155 was not associated with all-cause mortality (HR 0.95; 95% CI 0.82, 1.11; P = 0.54) in adjusted multivariable Cox regression models. Conclusion A differential correlation of miR-155 with CCN1 levels was found in patients with conventional DCM vs. those with DCMi, suggesting a potential role of these biomarkers only in conventional DCM. Further investigation of the pathophysiology of CCN1 in DCM is warranted, including -omics analyses.

Association of microRNA-192, pentraxin-3, and transforming growth factor-beta1 with estimated glomerular filtration rate in adults with diabetic nephropathy

ObjectiveNephropathy is among the most pervasive complications of diabetes; it frequently results in end-stage renal disease and even death. However, current biomarkers for diabetic nephropathy (DN) have limited diagnostic utility. Thus, this present study aims to examine the associations of estimated glomerular filtration rate (eGFR) with plasma concentrations of microRNA-192 (miR-192), pentraxin-3 (PTX-3), and transforming growth factor-beta1 (TGF-β1) to identify biomarkers able to distinguish late-stage from early-stage DN.MethodsIn total, 50 healthy volunteers and 271 diabetes patients were enrolled in this study. Participants were stratified into seven groups according to eGFR and glycated hemoglobin (HbA1c), healthy controls, diabetes without DN (G1), diabetes with mild renal impairment (G2), and 4 DN grades (G3a, G3b, G4, and G5).ResultsDN groups exhibited increases in serum miR-192 (p < 0.05), PTX-3(p < 0.05), TGF-β1(p < 0.05), malondialdehyde (p < 0.05), and xanthine oxidase (p < 0.05) levels and reductions in glutathione-s-transferase (p < 0.05) and superoxide dismutase (p < 0.05) compared to healthy controls. Among patients, eGFR was negatively correlated with miR-192, PTX-3, and TGF-β1, and positively correlated with HbA1c. In receiver operating characteristic curve analysis, miR-192 and PTX-3 demonstrated good diagnostic performance in distinguishing early from advanced DN.ConclusionElevated serum miR-192 and PTX-3 are associated with lower eGFR in DN, suggesting their utility as diagnostic and prognostic biomarkers.

Identification of serum miR-1246 and miR-150-5p as novel diagnostic biomarkers for high-grade serous ovarian cancer

Epithelial ovarian cancer (EOC) is one of the leading cancers in women, with high-grade serous ovarian cancer (HGSOC) being the most common and lethal subtype of this disease. A vast majority of HGSOC are diagnosed at the late stage of the disease when the treatment and total recovery chances are low. Thus, there is an urgent need for novel, more sensitive and specific methods for early and routine HGSOC clinical diagnosis. In this study, we performed miRNA expression profiling using the NanoString miRNA assay in 34 serum samples from patients with HGSOC and 36 healthy women. We identified 13 miRNAs that were differentially expressed (DE). For additional exploration of expression patterns correlated with HGSOC, we performed weighted gene co-expression network analysis (WGCNA). As a result, we showed that the module most correlated with tumour size, nodule and metastasis contained 8 DE miRNAs. The panel including miR-1246 and miR-150-5p was identified as a signature that could discriminate HGSOC patients with AUCs of 0.98 and 1 for the training and test sets, respectively. Furthermore, the above two-miRNA panel had an AUC = 0.946 in the verification cohorts of RT-qPCR data and an AUC = 0.895 using external data from the GEO public database. Thus, the model we developed has the potential to markedly improve the diagnosis of ovarian cancer.