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1.
Aims
To demonstrate that pregnancy-related complications are associated with alterations in cardiovascular and cerebrovascular microRNA expression. Gene expression of 32 microRNAs (miR-1-3p, miR-16-5p, miR-17-5p, miR-20a-5p, miR-20b-5p, miR-21-5p, miR-23a-3p, miR-24-3p, miR-26a-5p, miR-29a-3p, miR-33a-5p, miR-92a-3p, miR-100-5p, miR-103a-3p, miR-122-5p, miR-125b-5p, miR-126-3p, miR-130b-3p, miR-133a-3p, miR-143-3p, miR-145-5p, miR-146a-5p, miR-155-5p, miR-181a-5p, miR-195-5p, miR-199a-5p, miR-208a-3p, miR-210-3p, miR-221-3p, miR-342-3p, miR-499a-5p, and miR-574-3p) was assessed in placental tissues, compared between groups (35 gestational hypertension, 80 preeclampsia, 35 intrauterine growth restriction and 20 normal pregnancies) and correlated with the severity of the disease with respect to clinical signs, delivery date, and Doppler ultrasound parameters. Initially, selection and validation of endogenous controls for microRNA expression studies in placental tissues affected by pregnancy-related complications have been carried out.Results
The expression profile of microRNAs was different between pregnancy-related complications and controls. The up-regulation of miR-499a-5p was a common phenomenon shared between gestational hypertension, preeclampsia, and intrauterine growth restriction. Preeclamptic pregnancies delivering after 34 weeks of gestation and IUGR with abnormal values of flow rate in the umbilical artery demonstrated up-regulation of miR-1-3b. Preeclampsia and IUGR requiring termination of gestation before 34 weeks of gestation were associated with down-regulation of miR-26a-5p, miR-103a-3p and miR-145-5p. On the other hand, some of microRNAs (miR-16-5p, miR-100-5p, miR-122-5p, miR-125b-5p, miR-126-3p, miR-143-3p, miR-195-5p, miR-199a-5p, miR-221-3p, miR-342-3p, and miR-574-3p) were only down-regulated or showed a trend to down-regulation just in intrauterine growth restriction pregnancies requiring the delivery before 34 weeks of gestation.Conclusion
Epigenetic changes induced by pregnancy-related complications in placental tissue may cause later onset of cardiovascular and cerebrovascular diseases in offspring. 相似文献2.
Chen Bian Tongda Xu Hong Zhu Defeng Pan Yang Liu Yuanyuan Luo Pei Wu Dongye Li 《PloS one》2015,10(12)
Background
Luteolin (LUT), a kind of flavonoid which is extracted from a variety of diets, has been reported to convey protective effects of various diseases. Recent researches have suggested that LUT can carry out cardioprotective effects during ischemia/reperfusion (I/R). However, there have no reports on whether LUT can exert protective effects against myocardial I/R injury through the actions of specific microRNAs (miRs). The purpose of this study was to determine which miRs and target genes LUT exerted such function through.Methods
Expression of various miRs in perfused rat hearts was detected using a gene chip. Target genes were predicted with TargetScan, MiRDB and MiRanda. Anoxia/reoxygenation was used to simulate I/R. Cells were transfected by miR-208b-3p mimic, inhibitor and small interfering RNA of Ets1 (avian erythroblastosis virus E26 (v ets) oncogene homolog 1). MiR-208b-3p and Ets1 mRNA were quantified by real-time quantitative polymerase chain reaction. The percentage of apoptotic cells was detected by annexin V-fluorescein isothiocyanate/propidium iodide dyeing and flow cytometry. The protein expression levels of cleaved caspase-3, Bcl-2, Bax, and Ets1 were examined by western blot analysis. A luciferase reporter assay was used to verify the combination between miR-208b-3p and the 3’-untranslated region of Ets1.Results
LUT pretreatment reduced miR-208b-3p expression in myocardial tissue, as compared to the I/R group. And LUT decreased miR-208b-3p expression and apoptosis caused by I/R. However, overexpression of miR-208b-3p further aggravated the changes caused by I/R and blocked all the effects of LUT. Knockdown of miR-208b-3p expression also attenuated apoptosis, while knockdown of Ets1 promoted apoptosis. Further, the luciferase reporter assay showed that miR-208b-3p could inhibit Ets1 expression.Conclusion
LUT pretreatment conveys anti-apoptotic effects after myocardial I/R injury by decreasing miR-208b-3p and increasing Ets1 expression levels. 相似文献3.
Philip P. Becker Monika Rau Johannes Schmitt Carolin Malsch Christian Hammer Heike Bantel Beat Müllhaupt Andreas Geier 《PloS one》2015,10(11)
Objectives
Liver biopsies are the current gold standard in non-alcoholic steatohepatitis (NASH) diagnosis. Their invasive nature, however, still carries an increased risk for patients’ health. The development of non-invasive diagnostic tools to differentiate between bland steatosis (NAFL) and NASH remains crucial. The aim of this study is the evaluation of investigated circulating microRNAs in combination with new targets in order to optimize the discrimination of NASH patients by non-invasive serum biomarkers.Methods
Serum profiles of four microRNAs were evaluated in two cohorts consisting of 137 NAFLD patients and 61 healthy controls. In a binary logistic regression model microRNAs of relevance were detected. Correlation of microRNA appearance with known biomarkers like ALT and CK18-Asp396 was evaluated. A simplified scoring model was developed, combining the levels of microRNA in circulation and CK18-Asp396 fragments. Receiver operating characteristics were used to evaluate the potential of discriminating NASH.Results
The new finding of our study is the different profile of circulating miR-21 in NASH patients (p<0.0001). Also, it validates recently published results of miR-122 and miR-192 to be differentially regulated in NAFL and NASH. Combined microRNA expression profiles with CK18-Asp396 fragment level scoring model had a higher potential of NASH prediction compared to other risk biomarkers (AUROC = 0.83, 95% CI = 0.754–0.908; p<0.001). Evaluation of score model for NAFL (Score = 0) and NASH (Score = 4) had shown high rates of sensitivity (91%) and specificity (83%).Conclusions
Our study defines candidates for a combined model of miRNAs and CK18-Asp396 levels relevant as a promising expansion for diagnosis and in turn treatment of NASH. 相似文献4.
Introduction
Fibromyalgia (FM) is characterized by chronic pain and reduced pain threshold. The pathophysiology involves disturbed neuroendocrine function, including impaired function of the growth hormone/insulin-like growth factor-1 axis. Recently, microRNAs have been shown to be important regulatory factors in a number of diseases.The aim of this study was to try to identify cerebrospinal microRNAs with expression specific for FM and to determine their correlation to pain and fatigue.Methods
The genome-wide profile of microRNAs in cerebrospinal fluid was assessed in ten women with FM and eight healthy controls using real-time quantitative PCR. Pain thresholds were examined by algometry. Levels of pain (FIQ pain) were rated on a 0-100 mm scale (fibromyalgia impact questionnaire, FIQ). Levels of fatigue (FIQ fatigue) were rated on a 0-100 mm scale using FIQ and by multidimensional fatigue inventory (MFI-20) general fatigue (MFIGF).Results
Expression levels of nine microRNAs were significantly lower in patients with FM patients compared to healthy controls. The microRNAs identified were miR-21-5p, miR-145-5p, miR-29a-3p, miR-99b-5p, miR-125b-5p, miR-23a-3p, 23b-3p, miR-195-5p, miR-223-3p.The identified microRNAs with significantly lower expression in FM were assessed with regard to pain and fatigue. miR-145-5p correlated positively with FIQ pain (r=0.709, p=0.022, n=10) and with FIQ fatigue (r=0.687, p=0.028, n=10).Conclusion
To our knowledge, this is the first study to show a disease-specific pattern of cerebrospinal microRNAs in FM.We have identified nine microRNAs in cerebrospinal fluid that differed between FM patients and healthy controls. One of the identified microRNAs, miR-145 was associated with the cardinal symptoms of FM, pain and fatigue. 相似文献5.
Monica L. Bertoia Kimberly A. Bertrand Sherilyn J. Sawyer Eric B. Rimm Kenneth J. Mukamal 《PloS one》2015,10(8)
Background
Most studies of microRNA (miRNA) and disease have examined tissue-specific expression in limited numbers of samples. The presence of circulating miRNAs in plasma samples provides the opportunity to examine prospective associations between miRNA expression and disease in initially healthy individuals. However, little data exist on the reproducibility of miRNAs in stored plasma.Methods
We used Real-Time PCR to measure 61 pre-selected microRNA candidates in stored plasma. Coefficients of variation (CVs) were used to assess inter-assay reliability (n = 15) and within-person stability over one year (n = 80). Intraclass correlation coefficients (ICCs) and polychoric correlation coefficients were used to assess within-person stability and delayed processing reproducibility (whole blood stored at 4°C for 0, 24 and 48 hours; n = 12 samples).Results
Of 61 selected miRNAs, 23 were detected in at least 50% of samples and had average CVs below 20% for inter-assay reproducibility and 31 for delayed processing reproducibility. Ten miRNAs were detected in at least 50% of samples, had average CVs below 20% and had ICCs above 0.4 for within-person stability over 1–2 years, six of which satisfied criteria for both interassay reproducibility and short-term within-person stability (miR-17-5p, -191-5p, -26a-5p, -27b-3p, -320a, and -375) and two all three types of reproducibility (miR-27b-3p and -26a-5p). However, many miRNAs with acceptable average CVs had high maximum CVs, most had low expression levels, and several had low ICCs with delayed processing.Conclusions
About a tenth of miRNAs plausibly related to chronic disease were reliably detected in stored samples of healthy adults. 相似文献6.
Shoichi Miyamoto Shunsuke Usami Yasuhide Kuwabara Takahiro Horie Osamu Baba Daihiko Hakuno Yasuhiro Nakashima Masataka Nishiga Masayasu Izuhara Tetsushi Nakao Tomohiro Nishino Yuya Ide Fumiko Nakazeki Jun Wang Koji Ueyama Takeshi Kimura Koh Ono 《PloS one》2015,10(11)
Background
Recently, it has been reported that specific microRNA (miRNA) levels are elevated in serum and can be used as biomarkers in patients with cardiovascular diseases. However, miRNAs expression profiles and their sources in pericardial fluid (PF) are unclear.Methods and Results
The purpose of this study was to identify the levels of miRNAs in PF in relation to those in the serum in patients undergoing cardiac surgery. Serum (S) and PF from patients undergoing coronary artery bypass graft (CABG) due to stable angina pectoris (sAP) and unstable AP (uAP) and aortic valve replacement due to aortic stenosis (AS) were analyzed for the detection of miRNAs. We named these samples S-sAP, S-uAP, S-AS, PF-sAP, PF-uAP, and PF-AS, respectively. We first measured the levels of miR-423-5p, which was recognized previously as a biomarker for heart failure. miR-423-5p levels were significantly higher in PF than serum. Although there was no difference in miR-423-5p levels among the PF-AS, PF-sAP, and PF-uAP, its levels were significantly elevated in S-uAP compared with those in S-AS and S-sAP. In order to clarify the source of miR-423-5p in PF, we measured the levels of muscle-enriched miR-133a and vascular-enriched miR-126 and miR-92a in the same samples. miR-133a levels were significantly higher in serum than in PF, and it was elevated in S-uAP compared with S-AS. miR-126 level was significantly increased in serum compared with PF, and the level of miR-92a the similar tendency. miR-423-5p is located in the first intron of NSRP1. There is another miRNA, miR-3184, encoded in the opposite direction in the same region. In vitro experiments indicated that the duplex of miR-423-5p and miR-3184-3p was more resistant to RNase than the duplex of miR-423-5p and miR-133-3p, which may help to stabilize miR-423-5p in the PF.Conclusions
Our results suggested that miR-423-5p is enriched in PF, and serum miR-423-5p may be associate with uAP. Its expression pattern was different to that of muscle- and vascular-enriched miRNAs, miR-133a, miR-126, and miR-92a. 相似文献7.
8.
Mao Ouyang Yongxin Li Sheng Ye Jieyi Ma Liming Lu Weiming Lv Guangqi Chang Xiaoxi Li Qing Li Shenming Wang Wenjian Wang 《PloS one》2014,9(5)
Objective
Triple-negative breast cancer (TNBC) patients with truly chemosensitive disease still represent a minority among all TNBC patients. The aim of the present study is to identify microRNAs (miRNAs) that correlate with TNBC chemoresistance.Methods
In this study, we conducted miRNAs profile comparison between triple-negative breast cancer (TNBCs) and normal breast tissues by microRNA array. Quantitative real-time PCR (qRT-PCR) was utilized to confirm the specific deregulated miRNAs change trend. We used starBase 2.1 and GOrilla to predict the potential targets of the specific miRNAs. Cells viability and apoptosis assays were employed to determine the effect of alteration of the specific miRNAs in TNBC cells on the chemosensitivity.Results
We identified 11 specific deregulated miRNAs, including 5 up-regulated miRNAs (miR-155-5p, miR-21-3p, miR-181a-5p, miR-181b-5p, and miR-183-5p) and 6 down-regulated miRNAs (miR-10b-5p, miR-451a, miR-125b-5p, miR-31-5p, miR-195-5p and miR-130a-3p). Thereafter, this result was confirmed by qRT-PCR. We predicted the potential targets of the candidate miRNAs and found that they are involved in cancer-associated pathways. For the first time, we found that miR-130a-3p and miR-451a were down-regulated in TNBC. 9 of the 11 specific deregulated miRNAs were found to be associated with chemoresistance. In vitro assays, we found that up-regulation of either miR-130a-3p or miR-451a in MDA-MB-231 cells significantly changed the cells sensitivity to doxorubicin. The results suggest that TNBC chemotherapy might be affected by a cluster of miRNAs.Conclusion
The abnormal expression miRNAs in TNBC are mainly chemoresistance related. This might be part of reason that TNBC likely to evade from chemotherapy resulting in early relapse and high risk of death. To alter their expression status might be a potential therapeutic strategy to improve the outcome of chemotherapy for TNBC patients. 相似文献9.
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11.
Christian Schulte Simon Molz Sebastian Appelbaum Mahir Karakas Francisco Ojeda Denise M. Lau Tim Hartmann Karl J. Lackner Dirk Westermann Renate B. Schnabel Stefan Blankenberg Tanja Zeller 《PloS one》2015,10(12)
Background
Circulating microRNAs (miRNAs) have been described as potential diagnostic biomarkers in cardiovascular disease and in particular, coronary artery disease (CAD). Few studies were undertaken to perform analyses with regard to risk stratification of future cardiovascular events. miR-126, miR-197 and miR-223 are involved in endovascular inflammation and platelet activation and have been described as biomarkers in the diagnosis of CAD. They were identified in a prospective study in relation to future myocardial infarction.Objectives
The aim of our study was to further evaluate the prognostic value of these miRNAs in a large prospective cohort of patients with documented CAD.Methods
Levels of miR-126, miR-197 and miR-223 were evaluated in serum samples of 873 CAD patients with respect to the endpoint cardiovascular death. miRNA quantification was performed using real time polymerase chain reaction (RT-qPCR).Results
The median follow-up period was 4 years (IQR 2.78–5.04). The median age of all patients was 64 years (IQR 57–69) with 80.2% males. 38.9% of the patients presented with acute coronary syndrome (ACS), 61.1% were diagnosed with stable angina pectoris (SAP). Elevated levels of miRNA-197 and miRNA-223 reliably predicted future cardiovascular death in the overall group (miRNA-197: hazard ratio (HR) 1.77 per one standard deviation (SD) increase (95% confidence interval (CI) 1.20; 2.60), p = 0.004, C-index 0.78; miRNA-223: HR 2.23 per one SD increase (1.20; 4.14), p = 0.011, C-index 0.80). In ACS patients the prognostic power of both miRNAs was even higher (miRNA-197: HR 2.24 per one SD increase (1.25; 4.01), p = 0.006, C-index 0.89); miRA-223: HR 4.94 per one SD increase (1.42; 17.20), p = 0.012, C-index 0.89).Conclusion
Serum-derived circulating miRNA-197 and miRNA-223 were identified as predictors for cardiovascular death in a large patient cohort with CAD. These results reinforce the assumption that circulating miRNAs are promising biomarkers with prognostic value with respect to future cardiovascular events. 相似文献12.
Katia Marioni-Henry Debiao Zaho Pablo Amengual-Batle Nina Marie Rzechorzek Michael Clinton 《Acta veterinaria Scandinavica》2018,60(1):80
In this pilot study we investigated the expression of 14 microRNAs in the cerebrospinal fluid (CSF) of dogs with neoplastic, inflammatory and degenerative disorders affecting the central nervous system (CNS). CSF microRNA (miRNA) expression profiles were compared to those from dogs with neurological signs but no evidence of structural or inflammatory CNS disease. Seven miRNAs were easily detected in all samples: miR-10b-5p, miR-19b, miR-21-5p, miR-30b-5p, miR-103a-3p, miR-124, and miR-128-3p. Expression of miR-10b-5p was significantly higher in the neoplastic group compared to other groups. There was no relation between miRNA expression and either CSF nucleated cell count or CSF protein content. Higher expression of miR-10b-5p in the neoplastic group is consistent with previous reports in human medicine where aberrant expression of miR-10b is associated with various neoplastic diseases of the CNS. 相似文献
13.
Melissa A. Bellinger James S. Bean Melissa A. Rader Kathleen M. Heinz-Taheny Jairo S. Nunes Joseph V. Haas Laura F. Michael Mark D. Rekhter 《PloS one》2014,9(4)
Background
Acute kidney injury (AKI) is a syndrome characterized by the rapid loss of the kidney excretory function and is strongly associated with increased early and long-term patient morbidity and mortality. Early diagnosis of AKI is challenging; therefore we profiled plasma microRNA in an effort to identify potential diagnostic circulating markers of renal failure. The goal of the present study was to investigate the dynamic relationship of circulating and renal microRNA profiles within the first 24 hours after bilateral ischemia-reperfusion kidney injury in mice.Methodology/Principal Findings
Bilateral renal ischemia was induced in C57Bl/6 mice (n = 10 per group) by clamping the renal pedicle for 27 min. Ischemia-reperfusion caused highly reproducible, progressive, concordant elevation of miR-714, miR-1188, miR-1897-3p, miR-877*, and miR-1224 in plasma and kidneys at 3, 6 and 24 hours after acute kidney injury compared to the sham-operated mice (n = 5). These dynamics correlated with histologic findings of kidney injury and with a conventional plasma marker of renal dysfunction (creatinine). Pathway analysis revealed close association between miR-1897-3p and Nucks1 gene expression, which putative downstream targets include genes linked to renal injury, inflammation and apoptosis.Conclusions/Significance
Systematic profiling of renal and plasma microRNAs in the early stages of experimental AKI provides the first step in advancing circulating microRNAs to the level of promising novel biomarkers. 相似文献14.
Marie-France Seronde Mélanie Vausort Etienne Gayat Emeline Goretti Leong L. Ng Iain B. Squire Nicolas Vodovar Malha Sadoune Jane-Lise Samuel Thomas Thum Alain Cohen Solal Said Laribi Patrick Plaisance Daniel R. Wagner Alexandre Mebazaa Yvan Devaux GREAT network 《PloS one》2015,10(11)
Background
The biomarker value of circulating microRNAs (miRNAs) has been extensively addressed in patients with acute coronary syndrome. However, prognostic performances of miRNAs in patients with acute heart failure (AHF) has received less attention.Methods
A test cohort of 294 patients with acute dyspnea (236 AHF and 58 non-AHF) and 44 patients with stable chronic heart failure (CHF), and an independent validation cohort of 711 AHF patients, were used. Admission levels of miR-1/-21/-23/-126/-423-5p were assessed in plasma samples.Results
In the test cohort, admission levels of miR-1 were lower in AHF and stable CHF patients compared to non-AHF patients (p = 0.0016). Levels of miR-126 and miR-423-5p were lower in AHF and in non-AHF patients compared to stable CHF patients (both p<0.001). Interestingly, admission levels of miR-423-5p were lower in patients who were re-admitted to the hospital in the year following the index hospitalization compared to patients who were not (p = 0.0001). Adjusted odds ratio [95% confidence interval] for one-year readmission was 0.70 [0.53–0.93] for miR-423-5p (p = 0.01). In the validation cohort, admission levels of miR-423-5p predicted 1-year mortality with an adjusted odds ratio [95% confidence interval] of 0.54 [0.36–0.82], p = 0.004. Patients within the lowest quartile of miR-423-5p were at high risk of long-term mortality (p = 0.02).Conclusions
In AHF patients, low circulating levels of miR-423-5p at presentation are associated with a poor long-term outcome. This study supports the value of miR-423-5p as a prognostic biomarker of AHF. 相似文献15.
Lin Zheng Eric Leung Nelson Lee Grace Lui Ka-Fai To Raphael C. Y. Chan Margaret Ip 《PloS one》2015,10(6)
Objectives
The role of microRNAs in association with Mycobacterium tuberculosis (MTB) infection and the immunology regulated by microRNAs upon MTB infection have not been fully unravelled. We examined the microRNA profiles of THP-1 macrophages upon the MTB infection of Beijing/W and non-Beijing/W clinical strains. We also studied the microRNA profiles of the host macrophages by microarray in a small cohort with active MTB disease, latent infection (LTBI), and from healthy controls.Results
The results revealed that 14 microRNAs differentiated infections of Beijing/W from non-Beijing/W strains (P<0.05). A unique signature of 11 microRNAs in human macrophages was identified to differentiate active MTB disease from LTBI and healthy controls. Pathway analyses of these differentially expressed miRNAs suggest that the immune-regulatory interactions involving TGF-β signalling pathway take part in the dysregulation of critical TB processes in the macrophages, resulting in active expression of both cell communication and signalling transduction systems.Conclusion
We showed for the first time that the Beijing/W TB strains repressed a number of miRNAs expressions which may reflect their virulence characteristics in altering the host response. The unique signatures of 11 microRNAs may deserve further evaluation as candidates for biomarkers in the diagnosis of MTB and Beijing/W infections. 相似文献16.
Xian Wei Su Anna Ho Yin Chan Gang Lu Marie Lin Johnny Sze Jing Ye Zhou Wai Sang Poon Qiang Liu Vera Zhi Yuan Zheng George Kwok Chu Wong 《PloS one》2015,10(12)
Background
Aneurysmal subarachnoid hemorrhage (SAH) is a highly morbid and fatal condition with high rate of cognitive impairment and negative impact in quality of life among survivors. Delayed cerebral infarction (DCI) is one the major factors for these negative outcomes. In this study we compared the circulating microRNA profiles of SAH patients and healthy individuals, and the circulating microRNA profiles of SAH patients with and without DCI.Methods
Peripheral blood samples on Day 7 after the onset of SAH were subjected to microarray analysis with Affymetrix miRNA 3.0 array and quantitative PCR analysis. SAH patients with (N = 20) and without DCI (N = 20) and Healthy controls (N = 20) were included for analyses.Results
We demonstrated that 99 miRNAs were found to be dysregulated in the SAH patient group with DCI. 81 miRNAs were upregulated and 18 were downregulated. Findings from KEGG pathway analysis showed that miRNAs and target genes for axon guidance and TGF-beta signaling were involved, implying that the resulted differential miRNA expression pattern reflect the results of SAH instead of etiology of the disease. miR-132-3p and miR-324-3p showed distinctive upregulations in qPCR [miR-132: 9.5 fold (95%CI: 2.3 to 16.7) in DCI group and 3.4 fold (95%CI: 1.0 to 5.8) in Non-DCI group; miR-324: 4924 fold (95%CI: 2620 to 7228) in DCI group and 4545 fold (95%CI: 2408 to 6683) in non-DCI group]. However, there were no significant differences in fold changes between SAH patients with and without DCI [fold change ratios (mean+/-SD): 2.7+/-4.2 and 1.1+/-1.1 for miRNA-132 and miRNA-324].Conclusion
Our study demonstrated that as compared to healthy control, miR-132 and miR-324 showed a upregulation in both SAH DCI and Non-DCI groups. However, the differences between the SAH DCI and non-DCI groups were not statistically significant. 相似文献17.
18.
Objective
Plasma miRNAs represent potential minimally invasive biomarkers to monitor and predict outcomes from chemotherapy. The primary goal of the current study—consisting of patients with recurrent, platinum-resistant ovarian cancer—was to identify the changes in circulating miRNA concentrations associated with decitabine followed by carboplatin chemotherapy treatment. A secondary goal was to associate clinical response with changes in circulating miRNA concentration.Methods
We measured miRNA concentrations in plasma samples from 14 patients with platinum-resistant, recurrent ovarian cancer enrolled in a phase II clinical trial that were treated with a low dose of the hypomethylating agent (HMA) decitabine for 5 days followed by carboplatin on day 8. The primary endpoint was to determine chemotherapy-associated changes in plasma miRNA concentrations. The secondary endpoint was to correlate miRNA changes with clinical response as measured by progression free survival (PFS).Results
Seventy-eight miRNA plasma concentrations were measured at baseline (before treatment) and at the end of the first cycle of treatment (day 29). Of these, 10 miRNAs (miR-193a-5p, miR-375, miR-339-3p, miR-340-5p, miR-532-3p, miR-133a-3p, miR-25-3p, miR-10a-5p, miR-616-5p, and miR-148b-5p) displayed fold changes in concentration ranging from -2.9 to 4 (p<0.05), in recurrent platinum resistant ovarian cancer patients, that were associated with response to decitabine followed by carboplatin chemotherapy. Furthermore, lower concentrations of miR-148b-5p after this chemotherapy regimen were associated (P<0.05) with the PFS.Conclusions
This is the first report demonstrating altered circulating miRNA concentrations following a combination platinum plus HMA chemotherapy regiment. In addition, circulating miR-148b-5p concentrations were associated with PFS and may represent a novel biomarker of therapeutic response, with this chemotherapy regimen, in women with recurrent, drug-resistant ovarian cancer. 相似文献19.
Background
Circulating microRNAs (miRNAs) are emerging as promising biomarkers for human cancer. Osteosarcoma is the most common human primary malignant bone tumor in children and young adults. The objective of this study was to investigate whether circulating miRNAs in plasma could be a useful biomarker for detecting osteosarcoma and monitoring tumor removal dynamics.Methods
Plasma samples were obtained from 90 patients before surgery, 50 patients after one month of surgery, and 90 healthy individuals. The study was divided into three steps: First, initial screening of the profiles of circulating miRNAs in pooled plasma samples from healthy controls and pre-operative osteosarcoma patients using a TaqMan low density array (TLDA). Second, evaluation of miRNA concentration in individual plasma samples from 90 pre-operative osteosarcoma patients and 90 healthy controls by a quantitative real time PCR (qRT-PCR) assay. Third, evaluation of miRNA concentration in paired plasma samples from 50 pre- and post-operative osteosarcoma patients by qRT-PCR assay.Results
Four plasma miRNAs including miR-195-5p, miR-199a-3p, miR-320a, and miR-374a-5p were significantly increased in the osteosarcoma patients. Receiver operating characteristics curve analysis of the combined populations demonstrated that the four-miRNA signature could discriminate cases from controls with an area under the curve of 0.9608 (95% CI 0.9307-0.9912). These 4 miRNAs were markedly decreased in the plasma after operation. In addition, circulating miR-195-5p and miR-199a-3p were correlated with metastasis status, while miR-199a-3p and miR-320a were correlated with histological subtype.Conclusions
Our data suggest that altered levels of circulating miRNAs might have great potential to serve as novel, non-invasive biomarkers for osteosarcoma. 相似文献20.
Ilona Hromadnikova Katerina Kotlabova Lucie Hympanova Jindrich Doucha Ladislav Krofta 《PloS one》2014,9(12)