Detection of increased serum miR-122-5p and miR-455-3p levels before the clinical diagnosis of liver cancer in people with type 2 diabetes.
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ABSTRACT:
SUBMITTER: Lee HM
PROVIDER: S-EPMC8660865 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Breast cancer is one of the most malignant diseases in women worldwide. Serum microRNAs (miRNAs), with the characteristics of high sensitivity and specificity, have recently attracted more attentions to serve as potential biomarkers for tumor diseases. In this study, 194 breast cancer patients' serum samples were collected before surgery and enrolled into different groups based on their diagnostic information. To search for breast cancer diagnostic biomarkers, serum miRNAs were screened by microarray in pooled samples of healthy volunteers and breast cancer patients in different clinical stages. The miRNAs were further verified in each individual patient's serum samples in diagnostic and predictive sets. The serum level of miR-1915-3p was upregulated and miR-455-3p was downregulated significantly in breast cancer patients compared with healthy volunteers. Furthermore, the patients with infiltrating carcinoma or lymph node metastasis had a higher serum level of miR-1915-3p and lower serum level of miR-455-3p than patients with the carcinoma in situ or patients without lymph node metastasis. ROC analysis suggested that miR-1915-3p and miR-455-3p had the potential as a promising serum diagnostic and predictive biomarkers of breast cancer. miR-1915-3p was over-expressed in certain human breast cancer cells. Functional experiments in vitro showed that miR-1915-3p enhanced cell proliferative and migrational abilities. Overexpression of miR-1915-3p repressed target gene DUSP3 and activated ERK1/2. Collectively, this study provided a new insight that miR-1915-3p might play a role in the development of breast cancer and that serum miR-1915-3p and miR-455-3p could serve as diagnostic and predictive biomarkers for breast cancer.
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Project description:BACKGROUND:In this study, we discovered and validated candidate microRNA (miRNA) biomarkers for coronary artery disease (CAD). METHOD:Candidate tissue-derived miRNAs from atherosclerotic plaque material in patients with stable coronary artery disease (SCAD) (n=14) and unstable coronary artery disease (UCAD) (n=25) were discovered by qPCR-based arrays. We validated differentially expressed miRNAs, along with seven promising CAD-associated miRNAs from the literature, in the serum of two large cohorts (n=395?and n=1000) of patients with SCAD and UCAD and subclinical atherosclerosis (SubA) and controls, respectively. RESULT:From plaque materials (discovery phase), miR-125b-5p and miR-193b-3p were most upregulated in SCAD, whereas miR-223-3p and miR-142-3p were most upregulated in patients with UCAD. Subsequent validation in serum from patients with UCAD, SCAD, SubA and controls demonstrated significant upregulation of miR-223-3p, miR-133a-3p, miR-146-3p and miR-155-5p. The ischaemia-related miR-499-5p was also highly upregulated in patients with UCAD compared with the other groups (SCAD OR 20.63 (95% CI 11.16 to 38.15), SubA OR 96.10 (95% CI 40.13 to 230.14) and controls OR 15.73 (95% CI 7.80 to 31.72)). However, no significant difference in miR-499-5p expression was observed across SCAD, SubA and controls. MiR-122-5p was the only miRNA to be significantly upregulated in the serum of both patients with UCAD and SCAD. CONCLUSION:In conclusion, miR-122-5p and miR-223-3p might be markers of plaque instability.
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Project description:This is a prospective-retrospective study to determine if the expression of the miRNA’s miR-31-3p and miR-31-5p are prognostic of patient outcomes or predictive of the benefit from anti-EGFR therapy in stage III Colon Cancer. The present study will utilize FFPE tumor samples collected from patients enrolled in the PETACC-8 study conducted by the Fédération Francophone de Cancérologie Digestive (FFCD). This phase 3 clinical trial prospectively randomized fully resected stage III colon cancer patients to receive adjuvant treatment with either FOLFOX-4 plus cetuximab or FLOFOX-4 alone.
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Project description:Cardiogenic shock (CS) is a life-threatening emergency. New biomarkers are needed in order to detect patients at greater risk of adverse outcome. Our aim was to assess the characteristics of miR-21-5p, miR-122-5p, and miR-320a-3p in CS and evaluate the value of their expression levels in risk prediction. Circulating levels of miR-21-5p, miR-122-5p, and miR-320a-3p were measured from serial plasma samples of 179 patients during the first 5-10 days after detection of CS, derived from the CardShock study. Acute coronary syndrome was the most common cause (80%) of CS. Baseline (0 h) levels of miR-21-5p, miR-122-5p, and miR-320a-3p were all significantly elevated in nonsurvivors compared to survivors (p < 0.05 for all). Above median levels at 0h of each miRNA were each significantly associated with higher lactate and alanine aminotransferase levels and decreased glomerular filtration rates. After adjusting the multivariate regression analysis with established CS risk factors, miR-21-5p and miR-320a-3p levels above median at 0 h were independently associated with 90-day all-cause mortality (adjusted hazard ratio 1.8 (95% confidence interval 1.1-3.0), p = 0.018; adjusted hazard ratio 1.9 (95% confidence interval 1.2-3.2), p = 0.009, respectively). In conclusion, circulating plasma levels of miR-21-5p, miR-122-5p, and miR-320a-3p at baseline were all elevated in nonsurvivors of CS and associated with markers of hypoperfusion. Above median levels of miR-21-5p and miR-320a-3p at baseline appear to independently predict 90-day all-cause mortality. This indicates the potential of miRNAs as biomarkers for risk assessment in cardiogenic shock.
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Project description:The burden of pancreatic cancer (PanC) requires innovation in the current diagnostic approach. This study aimed to uncover new circulating microRNAs (miRNAs) that would distinguish patients with PanC from healthy subjects (HS) compared with the cancer antigen 19-9 (CA 19-9), and predict patients' clinical phenotypes and outcomes. MiRNA expression profiles in plasma were investigated by using a two-stage process. In a discovery phase, miRNAs levels were analyzed using the GeneChip™ miRNA 4.0 Affymetrix assay in 10 pools of plasma samples from PanC patients and HS; in a validation phase, significantly altered miRNAs were re-tested in independent cohorts of cancer patients and controls by droplet digital PCR (ddPCR). The diagnostic performance of the resulting miRNAs was compared to CA 19-9 determinations, and the associations of miRNAs plasma levels with patients' clinical phenotypes and outcomes were also taken into account. Bioinformatics selection of miRNAs differentially expressed in plasma uncovered miR-18a-5p, miR-122-5p, miR-1273g-3p, and miR-6126 as candidate oncogenic miRNAs in PanC. The ddPCR technology confirmed the significant over-expression of miR-122-5p, miR-1273g-3p, and miR-6126 in PanC compared to HS, in line with the trend of the CA 19-9 levels. Plasma levels of miR-1273g-3p, in combination with CA 19-9, showed higher power in distinguishing PanC patients from HS compared to the CA 19-9 tested alone, with a gain in both sensitivity and negative predictive value indicating a low false-negative rate (SE = 90.2% and NPV = 92.3% vs. SE = 82.1% and NPV = 87.9%). None of the oncogenic miRNAs were able to distinguish between a neoplastic and a proliferative/inflammatory disease of the pancreas, and were not able to stratify subjects according to the clinical risk for the disease. The only valuable association in PanC patients was found between miR-1273g-3p and tumor stage, and increased miR-122-5p levels emerged as independent negative prognostic factor for PanC patients (HR = 1.58, 95% CI = 1.03-2.43, p = 0.037). Our data highlighted a role for circulating miR-1273g-3p and miR-122-5p as new diagnostic and prognostic biomarkers for PanC.
| S-EPMC7010806 | biostudies-literature
Project description:Ischemic event in one arterial territory increases the risk of a subsequent ischemic event. Circulating microRNAs (miRs) emerge as a potential clinical tool to assess risk of subsequent atherothrombotic events such as cardiovascular death (CVD), myocardial infarction (MI) and ischemic stroke (IS). In this prospective study, we searched for athero-specific miRs related to cardiovascular event risk in patients with symptomatic coronary, carotid lesion, or both territories involvements. The choice of particular miRs was based on database research (Pub-Med, Bethesda, MD, USA) taking into consideration the relationship with development of atherosclerosis and potential prognostic value. Levels of circulating miRs (miR-1-3p, miR-16-5p, miR-34a-5p, mir-122-5p, miR-124-3p, miR-133a-3p, miR-133b, miR-134-5p, miR-208b-3p, miR-375 and miR-499-5p) were compared in 142 patients with an acute ischemic event resulting from carotid and/or coronary artery stenosis, who underwent revascularization for symptomatic lesion. A 6-year prospective evaluation of CVD/MI/IS risk was performed. Patients with two-territory as compared to single-territory involvement differed in levels of miR-1-3p (p = 0.016), miR-16-5p (p < 0.001), miR-34a-5p (p = 0.018), miR-122-5p (p = 0.007), miR-124-3p (p < 0.001) and miR-499-5p (p < 0.001). During follow-up, 62 (43.7%) episodes of CVD/MI/IS occurred. In multivariate Cox analysis, miR-122-5p (HR = 1.0006, 95%CI = 1.0001-1.0011) and peripheral artery disease (PAD) (HR = 2.16, 95%CI = 1.26-3.70) were associated with CVD/MI/IS risk; miR-1-3p (HR = 2.73, 95%CI = 1.22-6.12) and PAD (HR = 3.47, 95%CI = 1.88-6.41) with CVD; miR-122-5p (HR = 1.0001, 95%CI = 1.000-1.0002) and creatinine level (HR = 1.02, 95%CI = 1.01-1.04) with IS, and miR-16-5p (HR = 1.0004, 95%CI = 1.0001-1.0008) with MI. Expression of miR-1-3p, miR-16-5p and miR-122-5p during incident ischemia may be possible risk factors of secondary cardiovascular event(s).
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Project description:Polycystic ovarian syndrome (PCOS) is one of the most common gynecological endocrine disorders. MicroRNAs (miRNAs) play extensive roles in the pathogenesis of PCOS and can serve as potential diagnostic markers. However, most studies focused on the regulatory mechanisms of individual miRNAs, and the combined regulatory effects of multiple miRNAs remain unclear. The aim of this study was to identify the common targets of miR-223-3p, miR-122-5p, and miR-93-5p; and assess the transcript levels of some of these targets in PCOS rat ovaries. Transcriptome profiles of granulosa cells from PCOS patients were obtained from the Gene Expression Omnibus (GEO) database to identify differentially expressed genes (DEGs). A total of 1,144 DEGs were screened, 204 of which were upregulated and 940 were downregulated. According to the miRWalk algorithm, 4,284 genes were targeted by all three miRNAs at the same time, and intersection with DEGs was used to obtain candidate target genes. A total of 265 candidate target genes were screened, and the detected target genes were subjected to Gene ontology (GO) and KEGG pathway enrichment, followed by PPI network analysis. Then, qRT-PCR was used to determine the levels of 12 genes in PCOS rat ovaries. The expressions of 10 of these genes were found to be consistent with our bioinformatics results. In conclusion, JMJD1C, PLCG2, SMAD3, FOSL2, TGFB1, TRIB1, GAS7, TRIM25, NFYA, and CALCRL may participate in the development of PCOS. Our findings contribute to the identification of biomarkers that may promote the effective prevention and treatment of PCOS in the future.
| S-EPMC9977968 | biostudies-literature
Project description:Background:Lung cancer is the leading cause of cancer-related mortality worldwide, and non-small cell lung cancer (NSCLC) accounts for over 80% of all lung cancers. Serum microRNAs (miRNAs), due to their high stability, have the potential to become valuable noninvasive biomarkers. This present study was aimed to identify the serum miRNAs expression signatures for the diagnosis and prognosis of NSCLC using bioinformatics analysis. Methods:A total of 12 miRNAs profiling studies have been identified in Pubmed, Gene Expression Omnibus (GEO), and ArreyExpress databases. Differentially expressed miRNAs (DEmiRNAs) were analyzed according to GEO2R online tool and RRA method from R. Then, prediction of DEmiRNAs' target genes from TargetScan, PicTar, miRDB, Tarbase, and miRanda database. Furthermore, we using reverse transcription- quantitative polymerase chain reaction (RT-qPCR) to evaluate the expression levels of DEmiRNAs in serum samples obtained from NSCLC patients and healthy controls. Subsequently, the clinical significance of the tested miRNAs was determined using receiver operating characteristic (ROC) analysis and Cox regression analysis. Results:A total of 27 DEmiRNAs were identified and 5 of them (miR-1228-3p, miR-1228-5p, miR-133a-3p, miR-1273f, miR-545-3p) were significantly up-regulated and 4 of them (miR-181a-5p, miR-266-5p, miR-361-5p, miR-130a-3p) were significantly down-regulated in NSCLC patients compared with healthy controls. RT-qPCR validated that miR-1228-3p (P?=0.006) and miR-181a-5p (P?=0.030) were significantly differentially expressed in the serum of NSCLC patients and healthy controls. ROC analysis on miR-1228-3p and miR-181a-5p revealed the area under the curve (AUC) of 0.685 (95% confidence interval [CI], 0.563-0.806; P?=0.006) and 0.647 (95% CI, 0.506-0.758; P?=0.049). ROC analysis on miR-1228-3p combined miR-181a-5p revealed the AUC of 0.711 (95% CI, 0.593-0.828; P?=0.002). Multivariate Cox regression analysis demonstrated that the high serum miR-1228-3p level was an independent factor for the poor prognosis of NSCLC patients. Conclusions:Serum miR-1228-3p and miR-181a-5p are potential noninvasive biomarkers for the diagnosis and prognosis of NSCLC patients.
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Project description:Background:MicroRNAs (miRNA) play a relevant role in carcinogenesis, cancer progression, invasion, and metastasis. Thus, they can serve as diagnostic/prognostic biomarkers. The knowledge on circulating miRNAs for clear cell renal cell carcinomas (ccRCC) is limited. Our study was designed to identify novel biomarkers for ccRCC patients. Results:The serum small RNA expression profile was determined in 18 ccRCC and 8 patients with benign renal tumors (BRT) using small RNA sequencing. We detected 29 differentially expressed miRNAs (17 upregulated and 12 downregulated in ccRCC) in the expression profiling cohort. Based on the expression levels, we next validated serum miR-122-5p, miR-193a-5p, and miR-206 levels in an independent cohort (68 ccRCC, 47 BRT, and 28 healthy individuals) using quantitative real-time PCR. Serum expression levels of miR-122-5p and miR-206 were significantly decreased in ccRCC compared to healthy individuals. Both miRNAs were circulating at similar levels in ccRCC and BRT patients. miR-193a-5p expression levels were not different within the study cohort. High serum miR-122-5p and miR-206 levels were associated with adverse clinicopathological parameters: miR-122-5p levels were correlated with metastatic RCC and grade, and miR-206 with pT-stage and metastasis. Furthermore, high miR-122-5p and miR-206 serum levels were associated with a shorter period of progression-free, cancer-specific, and overall survival in patients with ccRCC. Conclusion:We identified serum miR-122-5p and miR-206 as novel non-invasive prognostic biomarkers for patients with ccRCC.
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Project description:Ischemic heart disease including myocardial infarction (MI) is a major cause of mortality and morbidity worldwide. In order to manage the acute myocardial infarction (AMI) outbreaks, novel biomarkers for risk prediction are needed. Recent studies have shown that circulating microRNAs (miRNAs) are promising biomarkers for cardiovascular diseases prediction. This study aimed to determine the possibility of circulating miRNAs used as biomarkers for AMI. The dynamic expression levels of miRNAs were examined before and after percutaneous coronary intervention (PCI) in patients. Circulating miR-17-5p, miR-126-5p, and miR-145-3p were selected and validated in 29 patients with AMI and 21 matched controls by quantitative real-time PCR. The expression levels of plasma miR-17-5p, miR-126-5p, and miR-145-3p were significantly increased in AMI patients. Receiver Operating Characteristic (ROC) analysis indicated that miR-17-5p, miR-126-5p, and miR-145-3p showed considerable diagnostic efficiency for AMI. Furthermore, we demonstrated that the combination of these three miRNAs managed to provide more accurate diagnosing of AMI.
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