Serum miR-122 Levels Research Articles

Serum MicroRNA-21 Negatively Relates to Expression of Programmed Cell Death-4 in Patients with Epithelial Ovarian Cancer

Background:Ovarian cancer is the third most common cancer of the female genital tract and the leading cause of cancer death associated with gynecologic tumors. MicroRNAs regulate at least 60% of human genes, including tumor suppressor genes and oncogenes and, thereby, can affect cancer risk.Aim of the work:We aimed to assess any diagnostic role for serum miR-21 as a biomarker in human ovarian cancer and to study relations with programmed cell death-4 (PDCD4), one of its target proteins, hoping to help explain heterogeneity of this cancer type and facilitate stratification of regimens for therapy.Subjects and Methods:A total of 60 newly diagnosed ovarian cancer cases and 30 apparently healthy females were recruited. Serum microRNA-21 levels were measured by TaqMan- Real time PCR assay and PDCD4 by ELISA.Results:Significant over-expression of serum miR-21 and lower serum PDCD4 levels were observed in ovarian cancer patients as compared to the control group. A statistically significant inverse correlation was also evident between miR-21 and PDCD4. However, no significant links were noted observed between miR-21 and tumor grade, stage or histopathological type.Conclusion:The present work showed significantly up-regulation of serum miR21 in the recruited group of patients and a significant inverse relation association between miR-21and PDCD4. These findings suggest that miR-21 may be used as a diagnostic biomarker for human ovarian cancer.

Early detection of cardiac surgery‑associated acute kidney injury by microRNA-21.

We tested the hypothesis whether microRNA-21 (miR-21) can detect CSA-AKI earlier than serum creatinine (sCr). A total of 103 patients scheduled to undergo cardiac surgery. CSA-AKI was defined as sCr > 0.3 mg/dl 24 h after surgery. The patients were divided into two groups according to whether or not developing AKI after surgery. Serum and urinary miR-21 were measured prior to, and 6, 12 and 24 h after surgery. Baseline serum and urinary levels of miR-21 in AKI group were lower than in non-AKI group. Moreover, the levels of miR-21 were significantly lower 6 h after surgery for serum, and 6 and 12 h after surgery for urine samples than those before surgery in AKI group. Area under the curve (AUC) of the receiver operating characteristic (ROC) values were 0.81 (95% CI: 0.65-0.97) for serum miR-21 (6 h after surgery), 0.90 (95% CI: 0.79-0.99) for urine (6 h after surgery), and 0.86 (95% CI: 0.71-0.98) for urine (12 h after surgery). While both postoperative serum and urinary miR-21 levels can predict AKI development, urinary miR-21 especially 6 h after surgery is a more reliable marker than serum miR-21 for detection of established CSA-AKI (Tab. 1, Fig. 3, Ref. 43).

Circulating Micro RNA- 21 and - 92a as Biomarkers of Colorectal Cancer

Background and study aim: Colorectal cancer (CRC) is a major cause of cancer-related deaths in both men and women. Colonoscopy is the most reliable tool for CRC diagnosis, but its complexity and costs hamper its wide application. There is a pressing need for new non-invasive biomarkers to improve early diagnosis of CRC. Aim was to assess serum micro RNA (miR) -21and miR-92a for diagnosis of CRC. Patients and Methods: This comparative cross sectional study was carried out on 50 subjects. The cases group comprised 35 consecutive treatment naive patients with sporadic CRC proved by colonoscopy and histopathology of the biopsied specimens as well as abdominal CT which all together helped in tumor staging applying TNM, Duke’s and MAC Coller stages. Serum carcinoembryonic antigen (CEA) and cancer antigen (CA) 19-9 were also assessed. Fifteen matched healthy subjects (with normal colonoscopy) served as the control group. Results: Serum levels of miR-21 and miR-92a were significantly higher (P<0.001) in cases compared to the control (5.53 ± 0.17≠4.82 ± 0.20 and 7.01 ± 0.234 ≠ 6.56 ± 0.20 log RU, respectively). Serum miR-21 and miR-92a levels revealed a significantpositive relation with tumor size and TNM and MAC Coller stages (P<0.05). No significant relationship was detected between either serum miR-21 or miR-92a levels with age or sex. Applying ROC curve, at a cutoff value of ≥5.25 log RU, serum miR-21 was 94.3% sensitive and 93.3% specific for detection of CRC with an AUC= 0.99 and serum miR-92a level at a cut off value ≥6.75 log RU, was 91.4% sensitive and 80% specific for detection of CRC with AUC= 0.91. When both markers were combined, the sensitivity and specificity were 97.1% and 93.3% respectively. Conclusion: Serum miR-21 and miR-92a levels represent a sensitive and specific tool for CRC diagnosis, with higher accuracy of miR-21.

Serum microRNA panel excavated by machine learning as a potential biomarker for the detection of gastric cancer.

Early detection of gastric cancer (GC) is crucial to improve the therapeutic effect and prolong the survival of patients. MicroRNAs (miRNAs) are a group of small non-protein-coding RNAs that function as repressors of diverse genes. We aimed to identify a microRNA panel in the serum of patients to predict GC non-invasively with high accuracy and sensitivity. Using six types of classifiers, we selected three markers (miR‑21-5p, miR-22-3p and miR-29c-3p) from a published miRNA profiling study (GSE23739) which was treated as a training set. The values of the area under the receiver operating characteristic (ROC) curves (AUCs) were 0.9437, 0.9456 and 0.9563 in the three classifiers [Compound covariate classifier, Diagonal linear discriminant analysis (DLDA) classifier and Support vector machine classifier], respectively. Then the panel was validated further in another two miRNA profiles in GEO (Gene Expression Omnibus) databases (GSE26595, GSE28700) with high AUC values as well. Next, we found that the serum levels of miR-21 were significantly higher in GC patients than levels in healthy controls by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) for confirmation, which was opposite to the serum levels of miR-22 and miR-29c (all P<0.0001). Finally, using bioinformatic tools, their biological mechanisms were elucidated by their predicted targets: Sp1 (miR-21) and PTEN (miR-22 and miR-29c). This miRNA panel is a non‑invasive and potential biomarker for GC.

Diagnostic accuracy of serum miR-122 and miR-199a in women with endometriosis.

To evaluate the value of serum microRNA-122 (miR-122) and miR-199a as reliable noninvasive biomarkers in the diagnosis of endometriosis. During 2015-2016, at a teaching hospital in Egypt, a prospective cohort study was conducted on 45 women with pelvic endometriosis and 35 women who underwent laparoscopy for pelvic pain but were not diagnosed with endometriosis. Blood and peritoneal fluid (PF) samples were collected; interleukin-6 (IL-6) was detected by enzyme-linked immunosorbent assay and miR-122 and miR-199a expression was measured by quantitative real-time polymerase chain reaction. The serum and PF levels of IL-6, miR-122, and miR-199a were significantly higher in women with endometriosis than in controls (P<0.001 for all comparisons). Serum miR-122 expression was positively correlated with serum IL-6 (r=0.597), PF IL-6 (r=0.603), PF miR-122 (r=0.934), serum miR-199a (r=0.727), and PF miR-199a (r=0.653). Serum miR-199a expression was positively correlated with serum IL-6 (r=0.677), PF IL-6 (r=0.678), PF miR-122 (r=0.744), and PF miR-199a (r=0.932). Serum miR-122 and miR-199a had a sensitivity of 95.6% and 100.0%, and a specificity of 91.4% and 100%, respectively, for the detection of endometriosis. Serum miR-122 and miR-199a were significantly increased in endometriosis, indicating that these microRNAs might serve as biomarkers for the diagnosis ofendometriosis.

Protective effects of crocin and zinc sulfate on hepatic ischemia-reperfusion injury in rats: a comparative experimental model study

ObjectivesThe aim of this study was to investigate the comparative protective effects of separate and combined pretreatment with Cr and ZnSO4 on serum levels of miR-122, miR-34a, liver function tests, protein expression of Nrf2 and p53, and histopathological changes following IR-induced hepatic injury. Materials and methodsFifty-six male Wistar rats randomly assigned into seven groups (n=8). Sham (S), IR, crocin pretreatment (Cr), and crocin pretreatment+IR (Cr+IR), ZnSO4 pretreatment (ZnSO4), ZnSO4 pretreatment+IR (ZnSO4+IR) and their combination (Cr+ZnSO4+IR) groups. In sham, ZnSO4 and Cr groups, animals received normal saline (N/S, 2ml/day), Cr (200mg/kg) and ZnSO4 (5mg/kg) for 7 consecutive days (intraperitoneally; i.p), then only laparotomy was performed. In IR, Cr+IR, ZnSO4+IR and Cr+ZnSO4+IR groups, rats received N/S, Cr and ZnSO4 with same dose and time, then underwent a partial (70%) ischemia for 45min that followed by reperfusion for 60min. Blood sample was taken for biochemical and microRNAs assay, tissue specimens were obtained for antioxidants, protein expression, histopathological and immunohistochemical evaluations. ResultsThe results showed that Cr and ZnSO4 increased antioxidants activity and expression of Nrf2, decreased serum levels of liver enzymes, miR-122, miR-34a, p53 expression and also ameliorated histopathological abnormality. However, their combination caused more improvement on IR-induced liver injury. ConclusionThis study demonstrated that Cr, ZnSO4 and their combination through increasing antioxidant activity and Nrf2 expression, decreasing the serum levels of liver enzymes, miR-122, 34a, p53 expression, and amelioration of histopathological changes, protected liver against IR-induced injury.

Decreased serum microRNA-21 level is associated with obesity in healthy and type 2 diabetic subjects

Background: Recently, much attention has been paid to the role of circulating microRNAs (miRNAs) as novel biomarkers for various diseases. The aim of this study was to investigate the level of a subset of miRNAs in serum samples of the diabetic and healthy subjects.Methods: Forty two healthy and 45 T2D subjects participated in this study. Serum miR-21, miR-126, and miR-146a levels were measured using real-time PCR.Results: There was no significant difference in the serum level of miR-21, miR-126, and miR-146a between the diabetic and non-diabetic groups. The level of miR-21 in obese non-diabetic and diabetic subjects was significantly lower than lean subjects. Correlation analyses in non-diabetic and diabetic groups revealed a significant negative correlation between the amount of miR-21 and body mass index, waist circumference, insulin, and HOMA-IR levels.Conclusions: A reduced level of miR-21 might associate with obesity and its related metabolic traits such as hyperinsulinaemia.

Association of miR-21, miR-126 and miR-605 gene polymorphisms with ischemic stroke risk.

We investigated whether three common microRNA polymorphisms (miR-21T>C [rs1292037], miR-126G>A [rs4636297] and miR-605T>C [rs2043556]) were associated with ischemic stroke (IS) risk in a Chinese population. The study population comprised 592 ischemic stroke patients and 456 normal controls. The polymorphisms were measured using Snapshot SNP genotyping assays and confirmed by sequencing. Relative expressions of miR-21, miR-126 and miR-605 were measured by quantitative real-time PCR. We found that miR-126 gene rs4636297 polymorphism was associated with decreased ischemic stroke risk (GA vs. GG: AOR=0.64, adjust P=0.025; AA vs. GG: AOR=0.32, adjust P=0.007; dominant model: AOR=0.58, adjust P=0.004). MiR-21 gene rs1292037 and miR-605 gene rs2043556 polymorphisms were not associated with ischemic stroke risk. In addition, compared with normal controls, serum miR-126 level was significantly decreased in ischemic stroke patients, while the miR-21 level was significantly increased. Importantly, patients carrying rs4636297 GA/AA genotypes had higher serum miR-126 level (P<0.05). MiR-126 gene rs4636297 polymorphism and serum miR-126/-21 levels are associated with ischemic stroke risk. Our data indicates that miR-126 and miR-21 play roles in the development of ischemic stroke.

Identification and characterization of interferon signaling-related microRNAs in occult hepatitis B virus infection

BackgroundOccult hepatitis B virus infection (OBI) is an important risk factor of liver cirrhosis and hepatocellular carcinoma. Type 1 interferon (IFN) signaling-related miRNAs were significantly associated with hepatitis B virus (HBV) infection. However, the characteristics of serum IFN signaling-related miRNAs in OBI remain unclear. Therefore, this study aimed to analyze the expression levels of serum IFN signaling-related miRNAs in OBI and to evaluate their potential values for OBI diagnosis.MethodsTwenty serum samples for training test (10 healthy controls and 10 OBI patients) and 438 validation serum samples from healthy controls, asymptomatic HBsAg carriers (ASC), and chronic hepatitis B (CHB) and OBI patients were collected. Expression levels of 32 IFN signaling-related miRNAs were analyzed in training and validation sets of samples using RT-qPCR.ResultsAmong 32 IFN signaling-related miRNAs, decreased miR-122 levels and increased miR-130a levels were detected in training OBI samples. Furthermore, the results from validation test showed that the mean serum miR-122 and miR-130a level was 2.28 ± 0.96 and 3.11 ± 0.93 in OBI subjects, respectively. Compared to the healthy controls, ASC and CHB patients, miR-122 levels were significantly downregulated, while miR-130a levels were significantly upregulated in OBI patients. ROC analysis indicated that miR-122 + miR-130a could differentiate OBI from healthy controls, ASC, and CHB (≥ 0.87 of AUC).ConclusionsOur study suggested that decreased serum miR-122 level and increased miR-130a level were significantly associated with OBI. Moreover, a combination of miR-122 and miR-130a could be served as a potential marker for OBI diagnosis.

Circulating miR-122 and miR-200a as biomarkers for fatal liver disease in ART-treated, HIV-1-infected individuals

Liver disease is one of the main contributors to the increased levels of morbidity and mortality seen in the HIV-1-infected, ART-treated population. Circulating miRNAs, particularly those located inside extracellular vesicles, are seen as promising biomarkers for a number of human disease conditions, including liver-related diseases. Here, we show that serum levels of miR-122 and miR-200a are greater in HIV/HCV co-infected individuals compared to HIV-1 mono-infected individuals. We also show that miR-122 and miR-200a are elevated in ART-treated, HIV-1-infected individuals prior to the development of fatal liver disease, suggesting that these miRNA may have some potential clinical utility as biomarkers. While this study is hypothesis generating, it shows clearly that both miR-122 and miR-200a are promising novel biomarkers for liver disease in the ART-treated, HIV-1-infected population.

Serum miR-210 and miR-155 expression levels as novel biomarkers for rheumatoid arthritis diagnosis

Background: MicroRNAs play a crucial role in the regulation of immune response. We hypothesised roles for serum miR-210 and miR-155 in the diagnosis of rheumatoid arthritis (RA) and relationships with the clinical and laboratory variables including erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), rheumatoid factor (RF), anti-cyclic citrullinated peptide (CCP) antibodies, tumour necrosis factor-alpha (TNF-α) and interleukin-1β (IL-1β).Methods: MiR-210 and miR-155 levels were identified by real-time polymerase chain reaction (PCR). TNF-α and IL-1β were measured by enzyme-linked immunosorbent assay and routine markers by standard techniques in 100 patients with RA and 100 individuals as healthy controls. Disease activity in the patients was assessed by DA-S28.Results: MiR-210 was lower in RA compared to controls [median/IQR 0.96 (0.8–1.24) vs. 4 (1.28–3.93), p < 0.001]. miR-210 correlated inversely with clinical and laboratory variables including TNF-α and IL-1β (both r = −0.96, p < 0.001). MiR-155 expression was increased in RA compared to controls [median/IQR 6 (3.5–8.1) vs. 1.0 (0.95–1.6), p < 0.001] and correlated with TNF-α and IL-1β (both r = 0.94, p < 0.001). In multivariate analysis, miR-210 and miR-155 were both independent diagnostic markers for RA, and both were associated with RA disease activity.Conclusion: Serum miR-210 and miR-155 levels are independent diagnostic markers for RA, out-performing several routine indices and reflect disease activity. Thus, miR-210 and miR-155 might serve as non-invasive biomarkers for the diagnosis of RA.

MiR-223 represents a biomarker in acute and chronic liver injury.

Dysregulation of miRNAs has been described in tissue and serum from patients with acute and chronic liver diseases. However, only little information on the role of miR-223 in the pathophysiology of acute liver failure (ALF) and liver cirrhosis is available. We analysed cell and tissue specific expression levels as well as serum concentrations of miR-223 in mouse models of acute (hepatic ischaemia and reperfusion, single CCl4 injection) and chronic (repetitive CCl4 injection, bile duct ligation (BDL)) liver diseases. Results were validated in patients and correlated with clinical data. The specific hepatic role of miR-223 was analysed by using miR-223-/- mice in these models. miR-223 expression was significantly dysregulated in livers from mice after induction of acute liver injury and liver fibrosis as well as in liver samples from patients with ALF or liver cirrhosis. In acute and chronic models, hepatic miR-223 up-regulation was restricted to hepatocytes and correlated with degree of liver injury and hepatic cell death. Moreover, elevated miR-223 expression was reflected by significantly higher serum levels of miR-223 during acute liver injury. However, functional in vitro and in vivo experiments revealed no differences in the degree of liver cell death and liver fibrosis as miR-223-/- mice behaved identical with wild-type (wt) mice in all tested models. miR-223 represents a promising diagnostic marker in a panel of serum markers of liver injury. Together with previously published data, our results highlight that the role of miR-223 in the pathophysiology of the liver is complex and needs further analysis.

Serum microRNA-122 and Wisteria floribunda agglutinin-positive Mac-2 binding protein are useful tools for liquid biopsy of the patients with hepatitis B virus and advanced liver fibrosis.

BackgroundNoninvasive methods to accurately and conveniently evaluate liver fibrosis are desirable. MicroRNA (miR) is one of the candidates. MiRs are small RNAs consisting of 19–25 nucleotides that negatively regulate many target genes at transcriptional levels. Recently, many researchers have focused on circulating miRs in the blood stream as biomarkers. Hepatic miR-122 has been reported to have an association with viral replication and hepatic fibrosis in chronic hepatitis B virus (HBV) and hepatic C virus (HCV) infection.MethodsWe measured serum miR-122 levels in HBV- and HCV-infected patients confirmed with liver biopsy. We also investigated a novel liver fibrosis marker Wisteria floribunda agglutinin-positive Mac-2 binding protein [WFA(+)-M2BP]. We evaluated the diagnostic usefulness of these markers in hepatic fibrosis and inflammation of patients with chronic viral infection.ResultsThe serum miR-122 levels of HBV-infected patients were higher than those of the control subjects. In HBV-infected patients, the serum miR-122 levels of patients with advanced liver fibrosis were significantly lower. Serum WFA(+)-M2BP was significantly higher dependent on both the staging of fibrosis and the grading of inflammatory activity in patients with both HBV and HCV infection. We also observed that higher serum WFA(+)-M2BP levels augmented the prediction of advanced liver fibrosis among HBV-infected patients with lower serum miR-122 levels.ConclusionsA lower serum miR-122 level is a useful predictor of advanced liver fibrosis in HBV-infected patients. Serum WFA(+)-M2BP could predict liver fibrosis in both HBV and HCV infection. The combination of these markers may result in the more accurate evaluation of liver fibrosis in HBV infection.

Circulating levels of miR-122 increase post-mortem, particularly following lethal dosing with pentobarbital sodium: implications for pre-clinical liver injury studies.

microRNA-122 (miR-122) is increasingly being measured in pre-clinical and clinical settings due to greater sensitivity and hepatic specificity compared to the gold standard liver injury biomarker alanine aminotransferase (ALT). In pre-clinical studies, various culling methods can be employed prior to collection of blood samples, including lethal injection with pentobarbital sodium (Pentoject). However, little is known about whether such an approach could alter the circulating levels of miR-122 and compromise the interpretation of data. We therefore exposed C57BL/6J mice to saline or the model hepatotoxin paracetamol and collected blood samples pre-cull (via tail bleed) and post-cull (via cardiac puncture following exposure to a rising concentration of CO2 or intraperitoneal injection of Pentoject). Compared to pre-cull levels there was a significant increase in serum miR-122 level in mice culled with CO2 and, to a much greater extent, in mice culled with Pentoject. As a result, whilst the serum level of miR-122 increased in Pentoject-culled animals exposed to paracetamol, the higher level in saline-treated mice rendered this difference statistically non-significant, in contrast to findings in animals culled with CO2. ALT levels were unaffected by sacrifice method. Consistent with the in vivo findings, exposure of primary mouse hepatocytes to Pentoject provoked a rapid and concentration-dependent release of miR-122 into the culture media. Thus, for optimal design and interpretation of data from pre-clinical liver injury studies in which miR-122 is to be used as a biomarker, we recommend that blood samples are collected pre-cull whenever possible, and that lethal injection with Pentoject is avoided.

Circulating miR-21 serves as a serum biomarker for hepatocellular carcinoma and correlated with distant metastasis.

Serum miRNAs have gained great popularity to act as circulating biomarkers of several cancers. In this study, we aimed to evaluate the diagnostic efficiency of serum miR-21 as novel biomarkers for patients with hepatocellular carcinoma (HCC) and other controls. A total of 533 individuals were recruited and conducted in a two-step analysis. The pilot group included 40 HCC patients and 40 healthy donors. The expression levels of miR-21 were significantly higher in primary HCC tissues than in adjacent noncancerous tissues (P<0.0001). HCC patients exhibited significantly higher serum levels of miR-21 than HD (P<0.0001). In the verification group, the mean serum levels of miR-21 in 175 patients with HCC were significantly higher than in 64 with CHB, 78 with LC and 136 HD (all P<0.0001). ROC curves demonstrated that the AUC of miR-21 was 0.849, sensitivity 82.1% and specificity 83.9%. Furthermore, serum miR-21 maintained its diagnostic efficiency in AFP-negative HCC subgroups with AUC 0.831, sensitivity 81.2% and specificity 83.2%. The serum levels of miR-21 could distinguish HCC from CHB and LC (AUC 0.789, sensitivity 76.9%, specificity 85.7% and AUC 0.814, sensitivity 80.8%, specificity 72.9%, respectively). In addition, the serum levels of miR-21 were significantly associated with clinical stage (P=0.006) and distant metastasis (P=0.000). Thus, our findings suggest that miR-21 together with AFP may help enhance the diagnosis of HCC, especially of AFP-negative HCC, and could distinguish HCC from CHB and LC.

Expression and differential diagnostic value of serum microRNA for invasive pulmonary aspergillosis

Objective: To explore the expression and the clinical diagnostic value of serum miR-21 for invasive pulmonary aspergillosis (IPA). Methods: Outpatients and inpatients from the Fourth Affiliated Hospital of Guangxi Medical University were included in the study during June 2014 to September 2015. The IPA group had 40 patients, male 22, female 18, aged 55-68 years (mean 60 ), while the control groups included 50 patients with pulmonary tuberculosis [male 23, female 27, aged 50-62 years (mean 55 )], 50 patients with lung cancer [male 30, female 20, aged 55-70 years (mean 62)], and 50 healthy controls [male 25, female 25, aged 50-67 years (mean 60) ]. Serum were obtained and the levels of miR-21 and galactomannan (GM test) and (1, 3)-beta-D-glucan (G test) were measured. The related indexes were analyzed by logistic regression and ROC curves. Results: The serum miR-21 expression in IPA and lung cancer patients were increased, the median values (P(25) and P(75)) being 0.42(0.31, 0.62)and 0.80(0.65, 0.94) respectively, both of which were significantly higher than those of the healthy controls [ 0.09(0.04, 0.15)] and the tuberculosis cases [ 0.08(0.03, 0.16)], P<0.001. The AUCs of miR-21 in IPA group, when compared to healthy controls, tuberculosis cases and lung cancer cases were 0.914, 0.897 and 0.863 respectively, with the Youden index being 0.780, 0.700 and 0.605 respectively. The serum levels of miR-21 in between 0.198 and 0.723 had preferable diagnostic accuracy. ROC analysis for miR-21 in IPA compared to healthy controls showed that the AUCs of miR-21 combined with G test or GM test were 0.992 and 0.966 respectively, the sensitivity being 95% (38/40) and 93% (37/40) respectively, the specificity being 98% (49/50) and 96% (48/50) respectively, and the Youden index being 0.930 and 0.885 respectively. If miR-21 was combined with G test and GM test, the AUC was 0.994, the sensitivity and the specificity being 98% (38/40) and 96% (48/50) respectively, and the Youden index increased to 0.935. ROC analysis for miR-21 in IPA compared to tuberculosis cases showed that when miR-21, G test and GM test were combined, the AUC was 0.984, the sensitivity and the specificity being 98% (38/40) and 90% (45/50) respectively, and the Youden index being 0.875. ROC analysis for miR-21 in IPA compared to lung cancer cases showed that the AUC for miR-21 with G test and miR-21 with GM test were 0.948 and 0.979 respectively, the Youden index being 0.725 and 0.895 respectively. When miR-21, G test and GM test were combined, the AUC was 0.998, the sensitivity and the specificity being 100% (40/40) and 98% (49/50) respectively, and the Youden index increased to 0.980. Conclusions: The serum level of miR-21 in IPA and lung cancer patients were significantly elevated. The serum level of miR-21 between 0.198 and 0.723 had preferable differential diagnostic accuracy, and therefore miR-21 may be regarded as an independent potential diagnostic serum marker of IPA. The diagnostic efficiency of miR-21 combined with G test and GM test may be more preferable, and remarkably increase the differential diagnosis of IPA from tuberculosis and lung cancer.

MicroRNA-155 and Anti-Müllerian Hormone: New Potential Markers of Subfertility in Men with Chronic Kidney Disease

Background/Aims: Men with terminal renal failure are often infertile. Anti-müllerian hormone (AMH), a marker of Sertoli cell function, is decreased among men with chronic kidney disease (CKD). Recently, a microRNA, miR-155, has been shown to be a potential marker for subfertility. We studied miR-155 and semen parameters in patients with CKD who were not yet on dialysis. We also aimed to study possible associations between AMH, miR-155, and semen parameters to evaluate them as markers of fertility. Methods: Thirty male patients with CKD 1–4 as well as 18 healthy controls were enrolled. Results: Serum levels of miR-155 were significantly higher among men with CKD stages 1–2 (4.51 ± 3.81 [p = 0.01]) and stages 3–4 (2.75 ± 1.77 [p = 0.006]) than in controls (1.09 ± 0.44). Sperm concentration was significantly lower among men with CKD 3–4 (42 ± 29) ×10⁶/mL compared to controls (88 ± 42) ×10⁶/mL (p = 0.011). High levels of miR-155 were associated with a relatively low sperm concentration (p = 0.02) and with a low total sperm number (p = 0.005). Low AMH levels were associated with a decreased percentage of motile sperm cells (p = 0.02). Conclusions: We conclude that men with stage 3–4 CKD had lower sperm concentrations than healthy fertile men and that increased serum miR-155 in men with stage 1–4 CKD was associated with semen parameters that indicate subfertility. Low AMH levels were associated with a low percentage of the total number of motile sperm cells. miR-155 and AMH may be potential markers of subfertility in men with CKD.

Evaluation of a combinational use of serum microRNAs as biomarkers for liver diseases

Circulating microRNAs (miRNA) have been widely recognized as a novel noninvasive biomarker in a variety of physiological and pathological conditions. In order to assess the sensitivity and reliability of potential miRNAs as diagnostic markers for liver disease related to viral infection, alcohol abuse, or chemical exposure, we collected serum samples from 326 participants and evaluated the single and combination diagnostic values of three serum miRNAs (miR-122, miR-125b, miR-192) compared with a conventional marker ALT. We found that serum miR-122 is significantly elevated in patients with active HBV. MiR-125b increased in HCV positive patients, whereas miR-192 and miR-122 were associated with chemical-induced liver injury. None of the aforementioned miRNAs were shown to increase significantly in alcohol-related liver injuries. Furthermore, we analyzed different combinations and found that a set of miR-122 and miR-125b enhanced the sensitivity of detecting liver injury. Among the 58 ALI/ALF patients, miR-122 responded more rapidly than ALT in successful treatments. Patients with spontaneous recovery from ALI/ALF showed significantly higher serum levels of miR-122 and miR-125b compared to non-recovered patients. In conclusion, our results suggest that the combination of miR-122 and miR-125b may serve as efficient biomarkers for liver injury and may be of a prognostic value in predicting ALI/ALF outcome.

Functional analysis of serum microRNAs miR-21 and miR-106a in renal cell carcinoma.

microRNAs (miRNAs) plays an important role in tumor development and progression and act as oncogenes or tumor suppressor genes in the carcinogenesis process. miRNA is stable in serum, and recent studies have demonstrated the feasibility of using circulating miRNA as biomarkers in cancer patients. However, currently, no serum biomarkers for the early diagnosis and prognosis of renal cell carcinoma (RCC) have been reported. Therefore, a new molecular marker for early diagnosis and evaluation of recurrence after surgery is required. Our purpose was to identify miRNA signatures that could distinguish the serum of RCC patients from matched healthy controls and validate identified miRNAs as potential biomarkers for RCC. Serum samples from 30 RCC patients were collected before and 1 month after surgery. 30 cancer-free blood donor volunteers with no history of any cancer were recruited from the same institute. miR-21 and miR-106a expression levels were determined by real-time PCR. The serum miR-21 level was significantly higher in RCC patients (median, 8.34) than in healthy control individuals (median, 0.70; p= 0.001). A month after surgery, serum miR-21 levels (median, 0.69) were significantly reduced (p= 0.032). The serum miR-106a level was higher in RCC patients (median, 8.99) compared with controls (median, 0.96; p= 0.000), while miR-106a levels (median, 1.01) were reduced a month after surgery (p= 0.028). The expression level of miR-21 and miR-106 a in RCC patients increased significantly, while miR-21 and miR-106a decreased after surgery. This outcome suggests that serum miR-21 and miR-106a expression level was closely related with kidney cancer tissue. We conclude that serum miR-21 and miR106a are expected to be molecular markers for RCC.

Predicative values of serum microRNA-22 and microRNA-126 levels for non-small cell lung cancer development and metastasis: a case-control study.

Presented study aims to explore the predictive values of serum microRNA-22 (miR-22) and miR-126 levels for non-small cell lung cancer (NSCLC) development and metastasis.A total of 127 NSCLC patients who were admitted in the First People's Hospital of Yancheng City from May, 2013 to May, 2015 were selected as the case group, including 71 cases of adenocarcinoma and 56 cases of squamous cell carcinoma. There were 112 healthy individuals selected as the control group. The qRT-PCR was performed to testify the serum miR-22 and miR-126 levels. Logistic regression analysis was conducted to analyze independent factors influencing NSCLC metastasis and receiver operating characteristic (ROC) curve was drawn to analyze the sensitivity and specificity of serum miR-22 and miR-126 levels in predicting NSCLC developments and metastasis.The serum miR-22 level was significantly higher in the case group than that in the control group, while the serum miR-126 level was lower in the case group as compared with that in the control group. Compared with squamous cell carcinoma patients, serum miR-22 level significantly increased, while serum miR-126 level decreased in patients with adenocarcinoma. Patients at III + IV stage showed increased serum miR-22 level and relatively decreased serum miR-126 level as compared to patients at I + II stage. Serum miR-22 level elevated in patients with metastasis; in contrast serum miR-126 level reduced in comparison to those without metastasis. In patients with familial inheritance, serum miR-22 level increased but serum miR-126 level decreased as compared to those without familial inheritance. The specificity and sensitivity of serum miR-22 and miR-126 levels in predicting NSCLC development were 99.11%, 84.30%, 82.68% and 96.40%, respectively. The specificity and sensitivity of serum miR-22 and miR-126 levels in predicting NSCLC metastasis were 59.74%, 96.00%, 84.00% and 62.30%, respectively.Results indicated that serum miR-22 and miR-126 levels may be used as the predicative biomarkers for NSCLC development and metastasis.