Diagnostic Accuracy Of miRNAs Research Articles

Diagnostic accuracy of circulating microRNAs for hepatitis C virus-associated hepatocellular carcinoma: a systematic review and meta-analysis

AimsThe purpose of this study was to perform an assessment of circulating microRNAs (miRNAs) as promising biomarker for hepatitis C virus (HCV)-associated hepatocellular carcinoma (HCV-HCC) through a meta-analysis.MethodsA comprehensive literatures search extended up to March 1, 2020 in PubMed, Cochrane library, Embase, Web of Science, Scopus and Ovid databases. The collected data were analyzed by random-effects model, the pooled sensitivity (SEN), specificity (SPE), positive and negative likelihood ratios (PLR and NLR), diagnostic odds ratio (DOR), and area under the curve (AUC) were used to explore the diagnostic performance of circulating miRNAs. Meta-regression and subgroup analysis were further carried out to explore the heterogeneity.ResultsA total of 16 articles including 3606 HCV-HCC patients and 3387 HCV patients without HCC were collected. The pooled estimates indicated miRNAs could distinguish HCC patients from chronic hepatitis C (CHC) and HCV-associated liver cirrhosis (HCV-LC), with a SEN of 0.83 (95% CI, 0.79–0.87), a SPE of 0.77 (95% CI, 0.71–0.82), a DOR of 17 (95% CI, 12–28), and an AUC of 0.87 (95% CI, 0.84–0.90). The combination of miRNAs and AFP showed a better diagnostic accuracy than each alone. Subgroup analysis demonstrated that diagnostic accuracy of miRNAs was better for plasma types, up-regulated miRNAs, and miRNA clusters. There was no evidence of publication bias in Deeks’ funnel plot.ConclusionsCirculating miRNAs, especially for miRNA clusters, have a relatively high diagnostic value for HCV-HCC from CHC and HCV-LC.

Non-Coding RNAs as Circulating Biomarkers for the Diagnosis of Intracranial Aneurysm: A Systematic Review and Meta-Analysis

BackgroundEarly diagnosis of intracranial aneurysm (IA) is arduous in the current situation, and no biomarker is available for the screening of IA. We here systematically evaluate the diagnostic value of circulating non-coding RNA (ncRNA) for the diagnosis of IA. MethodsWe searched PubMed, Web of Science, Embase, Scopus and Cochrane Library databases from inception to June 2020. We included studies that investigated the diagnostic performance of circulating ncRNAs for the diagnosis of IA. We performed Random-effect meta-analyses for the diagnostic test accuracy to calculate pooled estimates. Subgroup analyses and sensitivity analyses were conducted to explore the source of heterogeneity. ResultsThirteen studies, including 1,105 patients and 28 ncRNAs, were included. The pooled sensitivity and specificity were 0.80 (95% confidence interval [CI], 0.76–0.83) and 0.80 (95% CI, 0.76-0.84), respectively, and the area under the hierarchical summary receiver operating characteristic curve was 0.87 (95% CI, 0.84-0.89). The pooled positive and negative likelihood ratios were 3.97 (95% CI, 3.17-4.98) and 0.25 (95% CI, 0.21-0.31), corresponding with a diagnostic odds ratio of 15.63 (95% CI, 10.41-23.47). Subgroup analyses revealed that the diagnostic accuracy of miRNA, lncRNA and circRNA were not significantly different (p > 0.05). Circulating ncRNAs showed higher diagnostic accuracy for patients with unruptured IA than those with ruptured IA (p = 0.0122). ConclusionCurrent evidence suggests that the circulating ncRNA test could be an effective method for universal IA screening. Future clinical studies need to confirm the diagnostic role of specific ncRNAs.

Diagnostic value of microRNA panel in endometrial cancer: A systematic review.

Purpose: We conducted a systematic review to evaluate the overall diagnostic accuracy of miRNAs in detecting endometrial cancer.Materials and Methods: A systematic search of Medline, Embase, Cinahl and the Cochrane Controlled Register of Trials was performed to identify studies reporting on the diagnostic value of miRNA in EC patients. Included were diagnostic studies looking at miRNA expression in women diagnosed with endometrial cancer. Two reviewers independently selected studies and assessed quality of studies using the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) score system. Data extraction was completed and the vote-counting strategy was used to rank miRNAs.Results: 26 studies were included with a total number of 1,400 EC patients reporting on 106 differentially expressed miRNAs. The most frequently found up-regulated miRNA was miR-205 followed by miR-200c, -223, -182, -183 and -200a. In addition, miR-135b, miR-429, miR-141 and miR-200b were also frequently up-regulated. There was less consensus on down-regulated miRNAs.Conclusions: miRNAs yield a promising diagnostic biomarker potential in endometrial cancer, especially miR-205, the miR-200 family and miR-135b, -182, -183 and -223. However, no sufficient high quality data are available to draw hard conclusions. More research is needed to validate the diagnostic potential of these miRNAs in larger studies. In addition, the potential of urine as a non-invasive biofluid should be investigated in more detail.

Regulation of miRNAs as new tool for cutaneous vitality lesions demonstration in ligature marks in deaths by hanging

This study aims to demonstrate that the application of miRNA expression in forensic pathology, in cases of hanging, applying the method on skin samples. The proposed investigative protocol allowed us to highlight a different miRNA expression in the skin ligature marks of subjects who died by hanging compared to healthy skin control samples. The results obtained showed an increase in the expression of miRNAs recognized as regulators of the inflammatory response in skin lesions such as miR125a-5p and miR125b-5p. Furthermore, overexpression of additional miRNAs – miR214a-3p, miR128-3p, miR130a-3p, and miR92a-3p – with anti-inflammatory activity was highlighted. It was possible to document a statistical significance to control skin samples only for miR103a-3p (p < 0.05), miR214-3p and miR92a-3p (p < 0.01) The upregulation of miR222-3p and miR150-5p, respectively related to mast-cell activation and neutrophils after the application of traumatic stimuli supports the immunohistochemical data showed in literature. The diagnostic accuracy of miRNAs could expand the range of diagnostic tools available in the assessment of the vitality of a lesion.

A restricted signature of serum miRNAs distinguishes glioblastoma from lower grade gliomas.

BackgroundMalignant gliomas are the most common primary brain tumors in adults and challenging cancers for diagnosis and treatment. They remain a disease for which non-invasive, diagnostic and/or prognostic novel biomarkers are highly desirable. Altered microRNA (miRNA) profiles have been observed in tumor tissues and biological fluids. To date only a small set of circulating/serum miRNA is found to be differentially expressed in brain tumors compared to normal controls.Here a restricted signature of circulating/serum miRNA including miR-15b*,-23a, −99a, −125b, −133a, −150*, −197, −340, −497, −548b-5p and let-7c were investigated as potential non-invasive biomarkers in the diagnosis of glioma patients.MethodsSerum and tissues miRNAs expression in patients with brain cancers (n = 30) and healthy controls (n = 15) were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Relative expression was calculated using the comparative Ct method. Statistical significance (p ≤ 0,05) was determined using the Mann–Whitney rank sum and Fisher’s exact test. Diagnostic accuracy of miRNAs in distinguishing glioblastoma multiforme (GBM) from lower grade cancer was assessed by the Receiver Operating Characteristic (ROC) curve analysis.To validate the role of the identified miRNAs in cancer a comprehensive literature search was conducted using PubMed, Web of Science (Core Collection) and Scopus databases.ResultsWe observed a decrease of miR-497 and miR-125b serum levels depending on tumor stages with reduced level in GBM than lower grade tumors. The ROC curve analysis distinguishing GBM from lower grade cases yielded an area under the curve (AUC) of 0.87 (95 % confidence interval (CI) = 0.712–1) and of 0.75 (95 % CI = 0.533–0.967) for miR-497 and -125b, respectively. GBM patients are more likely to show a miR-497 and -125b down-regulation than the lower grade group (p = 0.002 and p = 0.024, respectively). These results were subsequently compared with evidence from 19 studies included in the final systematic review.ConclusionsAlthough multiple biomarkers are currently leveraged in the clinic to detect specific cancer types, no such standard blood biomolecules are used as yet in gliomas. Our data suggest that serum miR-497 and -125b could be a novel diagnostic markers with good perspectives for future clinical applications in patients with glioma.

The expression and clinical significance of microRNAs in colorectal cancer detecting.

MicroRNAs (miRNAs) are small non-coding RNAs which regulate gene expressions post-transcriptionally. Nowadays, various miRNAs have been found to be sensitive and specific biomarkers for the early diagnosis of colorectal cancer (CRC); however, there are different, even conflicting results in different publications concerning the diagnostic accuracy of miRNA. Therefore, we aim to conduct a meta-analysis of the relevant publications to comprehensively evaluate the diagnostic value of miRNAs in CRC detection. Several public databases such as PubMed, Embase, and Google Scholar were retrieved up to July 13, 2014. Sensitivity was applied to plot the summary receiver operator characteristic (SROC) curve against specificity. The area under the SROC curve (AUC) was calculated to assess the classified effects. STATA 12.0 software was used to perform all statistic analyses. A total of 29 articles, including 80 studies, were involved in our meta-analysis, 55 of which focus on single-miRNA assays and the other 25 on multiple-miRNA assays. Our results suggested that multiple-miRNA assays show a better diagnostic accuracy compared with single-miRNA assays. In addition, blood-based miRNA assays were more accurate than feces-based miRNA assays in CRC diagnosis. Our results also showed that miRNA diagnosis appear to be more accurate in Asians than in Caucasians. However, further researches are needed to validate our results and the feasibility of miRNAs as biomarkers in routine clinical diagnosis of CRC.

MicroRNAs used as novel biomarkers for detecting cancer metastasis.

The low survival rates of cancers are primarily due to late diagnosis and metastasis. Discriminating the metastasis is a crucial factor for prognosis and improving the survival rate of cancer patients. MicroRNAs (miRNAs) can regulate the expression of hundreds of downstream genes, which has a broad effect on the regulation of the whole cell cycle. Accumulating studies have found that the aberrant expression of miRNAs is associated with cancer genesis. The aim of this study is to evaluate the diagnostic value of miRNAs in detecting cancer metastasis. Medline, PubMed, Embase, and CNKI were searched for relevant articles. Sensitivity, specificity, positive and negative likelihood ratio (PLR, NLR) and diagnostic odds ratio (DOR), the summary receiver operator characteristic (SROC) curve and the calculated AUC (area under the SROC curve) were applied to explore the diagnostic accuracy of miRNAs in metastasis. Seven hundred seventy-one metastatic cancer patients and 552 non-metastatic cancer controls from 14 articles were involved in our meta-analysis. A sensitivity of 0.75 (95% confidence interval (CI), 0.72-0.79) and a specificity of 0.80 (95% CI, 0.76-0.84) were observed from metastatic patients and non-metastatic controls in the combined analysis. And the AUC was 0.83 (95% CI, 0.79-0.86). In addition, results from subgroup analyses suggested that a higher diagnostic value for metastasis was acquired in tissue sample other than blood sample (sensitivity, 0.82 versus 0.73; specificity, 0.84 versus 0.79; PLR, 5.0 versus 3.5; NLR, 0.22 versus 0.34; DOR, 23 versus 10; AUC, 0.88 versus 0.80). In summary, this meta-analysis proved the relatively high diagnostic value of miRNA in metastasis, which might be applied as a novel screening tool to detect metastasis along with other biomarkers. We also illustrated that tissue-based miRNAs may have a better diagnostic accuracy than blood-based miRNAs.

Abstract 1475: Plasma circulating miRNAs: a new potential biomarker for prostate cancer diagnosis

Abstract MicroRNAs (miRNAs) are a class of small, non-coding, single-stranded RNAs that negatively regulate gene expression mainly binding to 3′-untranslated region (UTR) of target mRNAs at the post-transcriptional level. Recent studies have demonstrated that aberrant expressions of miRNAs are closely associated with the development, invasion, metastasis and prognosis of various cancers including prostate cancer (PCa). However, while the majority of miRNAs are found at the intracellular level, a significant number of miRNAs have been observed outside the cells, including various body fluids. Circulating miRNAs act as ‘extracellular communication RNAs’ that could be particularly relevant in the context of neoplastic diseases and may be useful for early diagnosis as well as to predict the clinical outcome and the treatment response. The aim of this study was to investigate the hypothesis that changes in circulating miRNAs represent potentially useful minimally invasive biomarkers for the diagnosis, staging and prediction of outcome in prostate cancer. From 2012 onwards, consecutive men undergoing 12-core prostate biopsy at Sant’Andrea Hospital of Rome were enrolled into a prospective database. Indications for a prostatic biopsy were a PSA value ≥ 4 ng/ml and/or a positive digital rectal examination (DRE). We selected, as a training set, 32 patients with a mean age and PSA of 66.6 years (SD ±7.9) and 14.3 (range to 0,53-185) ng/ml, respectively. Among them 16 patients (50%) have cancer on biopsy; 8 with Gleason score 6; 3 with a Gleason score 7 and 5 with a Gleason score ≥8 and 16 patients (50%) are control individuals with non-neoplastic prostate disease (i.e. prostatitis). Profiling of microRNAs by deep sequencing allowed us to identify a “signature” of 27 microRNAs aberrant expressed in prostate cancer samples. Receiver-operator characteristics (ROC) curve analysis was used to evaluate the diagnostic accuracy of miRNAs for the final histopathological diagnosis of prostate cancer. An AUC of 0.77; 95%CI was observed for the diagnosis of prostate cancer using all 27 microRNAs, which is correlated with the Gleason score of the analyzed samples, while results to be independent from the respective values of serum PSA. Moreover, ROC curve analysis also highlighted a small subgroup consisting of 6 miRNAs with a high predictive power able to discriminate patients with prostate cancer (AUC = 0.805; 95%CI). This signature is under validation in an indipendent cohort of patients. These preliminary observations suggest that circulating miRNAs could represent promising biomarkers for non-invasive diagnosis in prostate cancer unrelated to PSA. Citation Format: Simona Giglio, Cosimo De Nunzio, Roberto Cirombella, Stefano Volinia, Emidio Luciani, Andrea Tubaro, Andrea Vecchione. Plasma circulating miRNAs: a new potential biomarker for prostate cancer diagnosis. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1475. doi:10.1158/1538-7445.AM2014-1475