microRNAs In Plasma Of Patients Research Articles

Evaluation of Micro RNAs in Aplastic Anemia Patients Presenting at Tertiary Care Hospital LUMHS, Hyderabad

Background: Bone marrow failure that results in pancytopenia causes aplastic anemia clinically. Aim: To determine the frequency of positive microRNAs in plasma of patients with aplastic anemia. Study Design: Descriptive cross-sectional study. Methodology: Aplastic patients were assessed for microRNAs level and patients were considered positive if the level was ≥2 Results: Majority 20(66.7%) of the patients was aged ≤30 years with only 10(33.3%) patients aged above 30 years. There were 22(73.3%) male and 8(26.7%) female patients with a male to female ratio of 2.8:1. Severe, very severe and non-severe aplastic anemia was recorded in 18(60%), 4(13.3%) and 8(26.7%) patients respectively. Taking a cut-off value of ≥27 IU/mL, 15(50%) patients were positive for microRNAs. Conclusion: It was concluded that a substantial proportion of patients with aplastic anemia were positive for microRNAs and the observed frequency increased with increasing severity of disease which suggested potential role of microRNAs in the diagnostic workup and management of aplastic patients. Keywords: Aplastic Anemia and Micro-RNAs.

Circulating plasma microRNA in patients with ACTH-dependent cushing's syndrome.

Circulating plasma microRNA in patients with ACTH-dependent cushing's syndrome.

Circulating Plasma MicroRNA in Patients With Active Acromegaly.

Excessive production of growth hormone causes marked multiorgan changes in patients with acromegaly, which may involve epigenetic mechanisms. To evaluate differences in circulating microRNAs (miRNAs) associated with chronic growth hormone overproduction in adults. A cross-sectional case-control study was conducted at a tertiary medical center. We enrolled 12 consecutive patients with acromegaly along with 12 age- and sex-matched controls in the discovery phase of the study and then extended this cohort to 47 patients with acromegaly and 28 healthy controls for the validation study. Plasma miRNAs were quantified by next-generation sequencing (NGS) in the discovery phase. Levels of selected miRNAs were validated on extended cohorts using reverse transcription quantitative polymerase chain reaction (RT-qPCR), compared between groups, and correlated with clinical parameters. Based on NGS data, we selected 3 plasma miRNAs downregulated in patients with acromegaly compared to healthy controls: miR-4446-3p -1.317 (P = 0.001), miR-215-5p -3.040 (P = 0.005), and miR-342-5p -1.875 (P = 0.013) without multiplicity correction for all 3 miRNAs. These results were confirmed by RT-qPCR in the validation phase for 2 miRNAs out of 3: miR-4446-3p (P < 0.001, Padjusted < 0.001), area under the receiver-operator curve (AUC) 0.862 (95% CI 0.723-0.936; P < 0.001) and miR-215-5p (P < 0.001, Padjusted < 0.001), AUC 0.829 (95% CI 0.698-0.907; P < 0.001) to differentiate patients with acromegaly from healthy controls. In a 2-phase experiment using 2 different techniques we found and validated the downregulation of plasma miR-4446-3p and miR-215-5p in patients with acromegaly compared to healthy subjects, which makes them promising biomarkers for further research.

Negative pressure wound therapy affects circulating plasma microRNAs in patients with diabetic foot ulceration

AimsNegative pressure wound therapy (NPWT) is commonly used in diabetic foot ulceration (DFU). The molecular mechanisms of NPWT action, particularly outside of the wound site, have not been described. We assessed NPWT’s effect on circulating miRNA expression levels in type 2 diabetes (T2DM) patients with DFU. MethodsWe examined 34 T2DM patients treated with either NPWT (n = 24) or standard therapy (ST, n = 10). The group assignment was based on clinical criteria and local practice. Next-generation sequencing-based microRNA expression was determined on the patient’s plasma collected before therapy and after 8 days. ResultsNPWT patients were similar to the ST group in terms of age, BMI, and HbA1c level; however, they differed by mean wound area (12.6 cm2 vs. 1.1 cm2 p = 0.0005). First, we analyzed the change of miRNA after NPWT or ST and observed an upregulation of let-7f-2 only in the NPWT group. Then, we analyzed the differential expression between NPWT and ST groups, looking at possible wound size effects. We found 12 differentially expressed miRNAs in pre-treatment comparison, including let-7f-2, while in post-treatment analysis we identified 28 miRNAs. The pathway enrichment analysis suggests that identified miRNAs may be involved in wound healing, particularly through angiogenesis. ConclusionWe found initial evidence that NPWT in T2DM patients with DFU affects miRNA expression in plasma. Additionally, some differences in plasma miRNA expression may be related to wound size.

Expression of plasma microRNA in patients with acromegaly

microRNA is a class of small non-coding RNA molecules involved in posttranscriptional regulation of gene expression. MicroRNAs are detectable in blood in stable concentrations, which makes them promising biomarkers for various diseases. to assess plasma microRNA expression in patients with active acromegaly compared with healthy controls. single-center, case-control study: assessment of plasma microRNA in patients with acromegaly compared with healthy controls. Fasting blood samples were drawn and centrifuged at +5С temperature and 3000 rpm for 20 minutes, then aliquoted and frozen at 80C until further analysis. MicroRNA extraction and library preparation was done according to manufacturers instructions. Expression analysis was performed on NextSeq sequencer. Bioinformatic analysis using atropos (adapted deletion), STAR (aligning), FastQC (quality control), seqbuster/seqcluster/miRge2 (microRNA annotation, isomiR and new microRNA search, expression analysis). Primary endpoint of the study differential expression of plasma microRNA in patients with acromegaly compared with healthy controls. we included 12 patients with acromegaly age 33.1 [20; 47], BMI 29.3 kg/m2 [24.0; 39.6], IGF-1 686.1 ng/mL [405.9; 1186.0] and 12 healthy subjects age 36.2 [26; 44], BMI 26.7 kg/m2 [19.5; 42.5], IGF-1 210.4 ng/mL [89.76; 281.90]; gender ratio for both groups 4 males, 8 females. The groups did not differ in gender (p=0.666), age (p=0.551) and BMI (p=0.378). We found decreased expression of four microRNAs in patients with acromegaly: miR-4446-3p 1.317 (p=0.001), miR-215-5p 3.040 (p=0.005), miR-342-5p 1.875 (p=0.013) and miR-191-5p 0.549 (p=0.039). However, none of these changes were statistically significant after adjustment for multiple comparisons (q 0.1). we found four microRNAs, which could potentially be downregulated in plasma of patients with acromegaly. The result need to be validated using different measurement method with larger sample size.

631-P: Negative Pressure Wound Therapy May Affect Circulating Plasma MicroRNAs in Patients with Diabetic Foot Ulceration

Background: Negative pressure wound therapy (NPWT) has been successfully used as treatment for diabetic foot ulceration (DFU). However, the molecular mechanisms of its action, especially outside of the wound bed, are not fully understood. We assessed the effect of NPWT on levels of circulating plasma microRNAs in patients with type 2 diabetes (T2DM) and DFU. Methods: We included 33 patients with T2DM and DFU - 23 individuals were assigned to NPWT and 10 to standard treatment (ST). Assignment to NWPT was based on routine clinical recommendations and not random. MicroRNAs enriched RNA was extracted from plasma at two time points: before treatment and after 8±1 days of treatment. Prepared small RNA libraries were sequenced on the NextSeq 500 sequencer (Illumina). Generated reads were aligned to mirBase 21 using Bowtie and counted using miRDeep2 software. Statistical analysis of differentially expressed microRNAs was performed via the edgeR package in the R environment. Results: The NPWT and ST groups were similar in terms of basic clinical characteristics, such as age (67.8 vs. 67.8 years, p=0.95) and HbA1c level (7% vs. 7.8%, p=0.15). We identified three miRNAs - miR-6842, miR-3690 and miR-11400 - that were expressed at a higher level post-treatment in the NPWT group as compared to the ST group. Interestingly, miR-3690 has been previously predicted to target mRNA of T-cell surface glycoprotein CD3 gamma chain (CD3G), therefore, it may be hypothesized that it affects the expression of CD3 and modulate the immune response. Additionally, in the NPWT group we observed a downregulation of miR-9 as compared to the initial level. MiR-9 is expressed in human monocytes and neutrophils upon activation. Thus, it may regulate the synthesis of proinflammatory mediators. Conclusions: We found initial evidence that short-term NPWT use in T2DM patients with DFU may affect miRNA expression in plasma and act through promoting immune system factors in the wound bed. Disclosure P. Kapusta: None. J. Hohendorff: Other Relationship; Self; Abbott, Ascensia Diabetes Care, Novo Nordisk A/S, Sanofi-Aventis. J. Zuranska: None. S. Borys: None. P. Konieczny: None. B.M. Kiec-Wilk: None. P.P. Wolkow: None. M. Malecki: Advisory Panel; Self; Abbott Laboratories, AstraZeneca, Bioton, Boehringer Ingelheim Pharmaceuticals, Inc., Lilly Diabetes, Merck Sharp &amp; Dohme Corp., Novartis Pharmaceuticals Corporation, Novo Nordisk Inc., Sanofi-Aventis. Speaker's Bureau; Self; Merck &amp; Co., Inc. Funding National Science Centre of Poland (2013/11/B/NZ5/03298)

Detection of Epstein-Barr virus (EBV)-encoded microRNAs in plasma of patients with nasopharyngeal carcinoma.

Nasopharyngeal carcinoma (NPC) latently infected by Epstein-Barr virus (EBV) expresses 40 EBV BART microRNAs (miRNAs). Difference in diagnostic efficacy of these miRNAs on NPC detection was observed. Here, we performed a comprehensive evaluation on the efficacy of these miRNAs. Quantitative polymerase chain reaction was performed on plasma nucleic acid isolated from patients with NPC and noncancer donors. For primary NPC, BART2-5P, BART6-3P, BART7-3P, BART7-5P, BART9-5P, BART11-3P, BART17-5P, and BART19-5P were significantly elevated. For recurrent NPC, plasma levels of BART2-3P, BART2-5P, BART5-3P, BART5-5P, BART6-3P, BART8-3P, BART9-5P, BART17-5P, BART19-3P, and BART20-3P were significantly increased. Area under curve (AUC) analysis showed that BART19-5P had the best performance to identify NPC which was serologically EBV DNA undetectable. For recurrent NPC, BART8-3P and BART10-3P had highest AUC value for identifying cancer in EBV DNA undetectable plasma. Our data supported the use of circulating EBV miRNAs in NPC and recurrent NPC detection.

Expression pattern of plasma microRNA in patients with precancerous diseases of colorectal cancer

Expression pattern of plasma microRNA in patients with precancerous diseases of colorectal cancer

Decreased Expression of Plasma MicroRNA in Patients with Methamphetamine (MA) Use Disorder.

Recent research have revealed that circulating miRNAs may offer noninvasive biomarkers for human disease, offering the prospect for earlier diagnosis, and improved precision of diagnoses. The diagnoses of drug use disorders is still mainly based on subjective report and no objective biomarkers available. Many animal and cell studies found that miRNAs were involved in substance use disorders, including alcohol, morphine, cocaine and amphetamine use disorders. However, no study on circulating miRNAs for drug use disorders so far. We investigated the differential expression of plasma miRNAs in 124 patients with methamphetamine (MA) use disorders. Based on the preliminary results from microarray screen, plasma expression of 6 candidate miRNAs were measured by Quantitative real-time RT-PCR. We found that the expression of miR181a, miR15b, miR- let-7e, miR- let-7d in plasma were decreased compared to normal controls. The expression of the altered miRNAs were negative correlated with drug use frequencies in past months. Our findings suggested that miR-181a, miR-15b, miR-let-7e and miR-let-7d may play a potential role in the pathology of MA use disorder, and could serve as a potential peripheral biomarker for MA use disorder when confirmed by future studies. Further study are needed to elucidate the molecular mechanism modulated by miRNAs and explore potential novel intervention targets.

Differential expression of microRNAs in plasma of patients with prediabetes and newly diagnosed type 2 diabetes.

MicroRNAs (miRNAs) are present in plasma and have emerged as critical regulators of gene expression at posttranscriptional level, and thus are involved in various human diseases, including diabetes. The objective of this study was to screen and validate differentially expressed plasma miRNAs in prediabetes and newly diagnosed type 2 diabetes (T2D). In this study, we screened differentially expressed plasma miRNAs in prediabetes and newly diagnosed T2D by miRNA microarray analysis, and validated the expression of candidate miRNAs using quantitative reverse transcription polymerase chain reaction assays. Furthermore, we performed gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathway analyses to disclose functional enrichment of genes predicted to be regulated by the differentially expressed miRNAs. Notably, our results revealed that hsa-miR-1249, hsa-miR-320b, and hsa-miR-572 (P<0.05) were differentially expressed among the three groups, which yielded an area under the receiver operator characteristics curve (AUC) of 0.784 [95% confidence interval (CI) 0.685-0.883], 0.946 (95% CI 0.906-0.985), and 0.843 (95% CI 0.766-0.920) discriminating T2D patients from NGT control groups, respectively, while the AUC was 0.887 (95% CI 0.818-0.957), 0.635 (95% CI 0.525-0.744), and 0.69 (95% CI 0.580-0.793) discriminating prediabetes patients from NGT control groups, respectively. In addition, GO and KEGG pathway analyses showed that genes predicted to be regulated by differentially expressed miRNAs were significantly enriched in several related biological processes and pathways, including the development of multicellular organisms, signal transduction, cell differentiation, apoptosis, cell metabolism, ion transport regulation, and other biological functions. Taken together, our results showed differentially expressed miRNAs in T2D and prediabetes. Plasma hsa-miR-1249, hsa-miR-320b, and hsa-miR-572 may serve as novel biomarkers for diagnosis and potential targets for the treatment for prediabetes and T2D.

Circulating Plasma Micro RNAs in Patients with Major Depressive Disorder Treated with Antidepressants: A Pilot Study

ObjectiveSignificant progress was made in the understanding etiopathogenic factors related to MDD, including through research on the role of micro RNAs (miRs). We investigated plasma miRs as potential markers for MDD in patients treated with antidepressants.MethodsAt the initiation and at the end of twelve weeks of treatment, blood samples were collected and a structured diagnostic interview and a standardized depression rating scale for the presence and severity of major depression were done. The average decrease in HAMD score was 76.89%. Plasma miR expression profiling was performed by real time PCR. The lists of up-regulated (cut-off=2) and down-regulated miRs were imported into the miRWalk2.0 algorithm and used for target predictions. KEGG database pathways analysis was used to retrieve the pathways significantly targeted by at least two of the miRs.ResultsOf the 222 miRs detected in plasma samples of MDD patients, 40 were differentially expressed after treatment. Twenty-three miRs were significantly overexpressed with fold changes between 1.85 and 25.42, and 17 miRs were significantly downregulated with fold changes from 0.28 to 0.68. Pathway analysis revealed a list of 29 pathways for up-regulated miRs, and 20 pathways for down-regulated miRs. Six dysregulated miRs are common to all the top five pathways (Wnt signaling, Cancer, Endocytosis, Axon guidance, MAPK signaling): miR-146a-5p, miR-146b-5p, miR-221-3p, miR-24-3p, miR-26a-5p.ConclusionOverall, our miRWalk analysis of changes in plasma microRNAs after treatment of patients with major depression might open a new avenue for the understanding of Escitalopram mode of action and for its side effects.

Plasma circulating-microRNA profiles are useful for assessing prognosis in patients with cytogenetically normal myelodysplastic syndromes

Myelodysplastic syndromes are a heterogeneous group of clonal bone marrow hematopoietic stem cell disorders characterized by ineffective hematopoiesis and peripheral cytopenias. Chromosomal abnormalities and gene mutations have been shown to have essential roles in pathogenesis and correlate with prognosis. Molecular markers, however, are not integrated into currently used prognostic systems. The goal of this study is to identify plasma microRNAs useful for classification and risk stratification of myelodysplastic syndromes. We applied a novel, high-throughput digital quantification technology (NanoString) to profile microRNA expression in plasma samples of 72 patients with myelodysplastic syndromes and 12 healthy individuals. We correlated these results with overall survival. In patients with myelodysplastic syndromes associated with a diploid karyotype, we identified and validated a 7-microRNA signature as an independent predictor of survival with a predictive power of 75% accuracy (P=0.008), better than those of the International Prognostic Scoring Systems and the MD Anderson Prognostic Lower Risk Prognostic Model. We also identified differentially expressed plasma microRNAs in patients with myelodysplastic syndromes versus healthy individuals and between patients with myelodysplastic syndromes associated with different cytogenetic features. These results validate the utility of circulating-microRNA levels as noninvasive biomarkers that can inform the management of patients with myelodysplastic syndromes. Our findings also shed light on interactions of gene regulation pathways that are likely involved in the pathogenesis of myelodysplastic syndromes.

Circulating miR-323-3p and miR-652: Candidate markers for the presence and progression of acute coronary syndromes

BackgroundThe prognostic utility of circulating plasma microRNA in patients with acute coronary syndromes (ACS) has been proposed but not yet demonstrated. We set out to investigate circulating microRNA levels in patients incurring recent ACS and examined associations with neurohormones, cardiac structure and function, and survival over 5years of follow-up. MethodsAn initial screen of 375 microRNAs was performed in 35 ACS patients and 16 healthy controls. Candidates identified from the initial screen (miR-323-3p, miR-652, miR-27b, miR-103 and miR-208a) were validated in a further cohort of 200 patients at baseline (~30days post-ACS) and at 4 and 12months post-ACS, and compared with 100 controls. ResultsIn the validation cohort, significantly higher levels in patients were replicated for miR-323-3p, miR-652 and miR-27b (10-fold, 2.3-fold and 2.3-fold, respectively, adjusted p<0.05). Lower levels of miR-103 were not replicated and miR-208a was undetectable. From baseline to 4months post-admission, miR-323-3p and miR-652 remained elevated in patients compared to controls (adjusted p<0.01), with no further change in levels between 4 and 12months; whereas miR-27b fell to control levels by 4months. Baseline levels of miR-652 in the lowest tertile were significantly associated with readmission for heart failure (log-rank p<0.001). In combination with NT-proBNP and LVEF, miR-652 significantly improved risk stratification (p<0.001). ConclusionsOur study identifies miR-652 as a novel candidate biomarker for post-ACS prognosis beyond existing biomarkers of LVEF and NT-proBNP. Moreover circulating miR-323-3p was markedly elevated in patients for at least a year post-ACS and may be a stable biomarker for ACS.

Circulating microRNAs: Understanding the Limits for Quantitative Measurement by Real‐Time PCR

Ever since the discovery of small, non-coding RNAs in circulation, microRNAs have gained significant attention as biomarkers or, in some instances, regulators of disease and/or associated complications. Until now, most articles published use real-time quantitative PCR (qPCR) for assessment of

Abstract 18427: Impact of Medication on Quantification of Plasma MicroRNAs in Patients With Cardiovascular Disease

Background: MicroRNAs are small non-coding RNAs that are detectable in the blood. Circulating levels of microRNAs have been measured in various epidemiological studies, but the effects of medication are unclear. To address these uncertainties, we assessed how plasma microRNAs change in response to platelet inhibition and heparin administration. We also correlated plasma levels of microRNAs with existing markers of platelet activation. Methods and Results: 92 microRNAs were assessed in a dose-escalation study with aspirin and prasugrel in healthy volunteers (n=11). Plasma levels of platelet microRNAs, such as miR-223, miR-191 and others decreased on platelet inhibition. Findings were confirmed by individual TaqMan qPCR assays and validated in an independent cohort of patients with symptomatic carotid stenosis (n=33). In a cohort of patients on dual anti-platelet therapy 30 days post myocardial infarction (n=129), plasma levels of most platelet microRNAs were positively correlated to the VASP assay. Levels of miR-126 were also significantly associated with results from the VerifyNow P2Y12 aggregation assay. No association was observed with optical aggregometry with arachidonic acid or ADP. When platelet-poor plasma was collected at different time points from patients undergoing PCI (n=20) or diagnostic angiography with (n=7) and without (n=10) heparin administration, heparin was found to have pronounced effects on the assessment of the exogenous C. elegans spike-in control (decrease by &gt;3 cycles), which disappeared six hours after the heparin bolus. Normalisation of individual microRNAs with the average cycle threshold value of all microRNAs provided a suitable alternative to normalization with exogenous C. elegans spike-in control in this setting. Conclusions: Our studies provide evidence for a correlation of plasma microRNAs with commonly used methods in platelet testing. They also highlight that microRNA levels are sensitive to medication, in particular antiplatelet and anticoagulation therapy. This has to be taken into account when designing studies to investigate the relation of circulating microRNAs to cardiovascular disease.

Differential expression of microRNAs in plasma of patients with laryngeal squamous cell carcinoma: potential early-detection markers for laryngeal squamous cell carcinoma

Altered microRNA (miRNA) expression has been found in many cancers, including lung, breast, prostate, bladder and colorectal cancer. Many recent studies have demonstrated that aberrant plasma miRNAs were also found in various types of cancers. However, the alteration in plasma miRNA expressions in laryngeal squamous cell carcinoma (LSCC) remains unclear. The present study aimed to investigate the alterations in plasma miRNAs in LSCC. In the present study, the expression profiles of 738 miRNAs in plasma from 20 patients and 44 healthy subjects were evaluated using high-throughput real-time quantitative polymerase chain reaction. Our results demonstrated that expression levels of 17 miRNAs were significantly upregulated in patients with LSCCs when compared to control group (p<0.05). Expression levels of nine miRNAs were found significantly downregulated in LSCC patients (p<0.05). In addition, 17 miRNAs were expressed only in LSCC group, and five of these miRNAs (miR-331-3p, 603, 1303, 660-5p and 212-3p) are LSCC specific and never seen before in plasma of any human subject. In conclusion, our study suggests that detecting these LSCC-specific miRNAs in plasma might serve as novel noninvasive biomarkers for LSCC.

Circulating MicroRNA in Digestive Tract Cancers

d t For many decades, cell-free nucleic acids have been known to be present in peripheral blood. Several tudies have identified tumor-specific and/or tumor-assoiated alterations in the circulating nucleic acids of paients with various cancers. In recent years, cell-free miroRNA (miRNA) have been stably detected in the plasma nd serum, like other molecules; their presence in the lood has attracted the attention of researchers due to heir potential use as valuable blood biomarkers.1 MiRNAs are short, noncoding RNAs that play important roles in various physiologic and developmental processes. The mature miRNAs are produced from long primary transcripts through 2 sequential cleavage steps. The long primary miRNA transcript is cleaved by the Drosha complex in the nucleus, generating intermediate precursor miRNA. Precursor miRNA is transported by exportin-5 from the nucleus into the cytoplasm, and then subjected to further cleavage by a Dicer RNAase III enzyme, generating a short double-strand miRNA. One strand (guided strand) of mature miRNA is then incorporated into the RNA-induced silencing complex and subsequently hybridize to the 3=-untranslated region of their target mRNAs to repress translation or degrade these mRNAs. Thus, a single miRNA can influence the expression of hundreds of genes and allow them to function in a coordinated manner. Therefore, miRNAs have been implicated as key molecules in all cellular processes. Numerous studies have shown that alterations in miRNA expression correlate with various diseases, including the development and progression of cancer, and some miRNAs can function as oncogenes or tumor suppressors. These findings have opened up a new and interesting field in the diagnosis of cancer and the treatments of cancer patients. Mitchell et al2 first demonstrated that circulating miRNAs had the potential to be new biomarkers in patients with solid cancers. In recent years, several papers have demonstrated that circulating miRNAs can also be detected in the peripheral blood of patients with digestive tract cancers. Although the origins and physiologic functions of cell-free miRNAs in the blood remain to be fully elucidated, a noninvasive assay for miRNAs should be developed to exploit these molecules as potential diagnostic and prognostic biomarkers. This assay undoubtedly contributes to an improvement in the clinical outcomes of cancer patients. In this article, we review the current state of biological and clinical research regarding circulating miRNAs of digestive tract cancer patients and discuss the future perspectives.

Circulating microRNAs in plasma of patients with oesophageal squamous cell carcinoma

Background:Several recent studies demonstrated that microRNAs (miRNAs) are stably detectable in plasma/serum. We hypothesised that plasma miRNAs concentrations contributed to potential biomarkers in patients with oesophageal squamous cell carcinoma (ESCC).Methods:We selected three oncogenic miRNAs (miR-21, miR-184, miR-221) and one tumour suppressive miRNA (miR-375), which are frequently reported in squamous cell carcinoma, as candidate targets for this plasma miRNA assay. This study was divided into three steps: (1) Determination of appropriate plasma miRNAs in preliminary tests. (2) Evaluation of whether the plasma miRNA assays could monitor tumour dynamics. (3) Validation study on the clinical application of plasma miRNA assays in 50 ESCC patients and 20 healthy volunteers.Results:(1) In preliminary tests, the plasma level of miR-21 was significantly higher (P=0.0218) and that of miR-375 (P=0.0052) was significantly lower in ESCC patients than controls. (2) The high plasma miR-21 levels reflected tumour levels in all cases (100%). The plasma level of miR-21 was significantly reduced in postoperative samples (P=0.0058). (3) On validation analysis, the plasma level of miR-21 tended to be higher in ESCC patients (P=0.0649), while that of miR-375 was significantly lower (P<0.0001) and the miR-21/miR-375 ratio was significantly higher (P<0.0001) in ESCC patients than in controls. The value of the area under the receiver-operating characteristic curve (AUC) was 0.816 for the miR-21/miR-375 ratio assay. Patients with a high plasma level of miR-21 tended to have greater vascular invasion (P=0.1554) and to show a high correlation with recurrence (P=0.0164).Conclusion:Detection of circulating miRNAs might provide new complementary tumour markers for ESCC.

Circulating microRNAs in plasma of patients with gastric cancers

Background:We examined plasma microRNA (miRNA) concentrations from patients with gastric cancers (GCs) to assess their clinical application for diagnosing and monitoring diseases.Methods:We initially investigated the appropriateness of plasma miRNA assay, and then compared plasma miRNA results with the expressions in cancer tissues from eight GC patients, and also compared plasma miRNAs between pre- and post-operative paired samples from 10 GC patients. Then, plasma miRNAs (miR-17-5p, miR-21, miR-106a, miR-106b and let-7a) were analysed in 69 GC patients and 30 healthy volunteers in total.Results:The initial analysis showed that miRNAs were stable and detectable in all plasma samples, and the plasma miRNA levels reflected the tumour miRNAs in most cases. The levels of these miRNAs were significantly reduced in post-operative samples. In large-scale analysis, the plasma concentrations of miRNAs (miR-17-5p, miR-21, miR-106a, miR-106b) were significantly higher in GC patients than controls (P=0.05, 0.006, 0.008 and <0.001 respectively), whereas let-7a was lower in GC patients (P=0.002). The values of the area under the receiver-operating characteristic curve were 0.721 for the miR-106b assay and 0.879 for the miR-106a/let-7a ratio assay.Conclusion:Detection of circulating miRNAs might provide new complementary tumour markers for GC.

Differential expression of microRNAs in plasma of patients with colorectal cancer: a potential marker for colorectal cancer screening

Objective:MicroRNAs (miRNAs) have been shown to offer great potential in the diagnosis of cancer. We investigated whether plasma miRNAs could discriminate between patients with and without colorectal cancer (CRC).Methods:This study...