Blood Circulating miRNA Pairs as a Robust Signature for Early Detection of Esophageal Cancer.
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ABSTRACT:
SUBMITTER: Song Y
PROVIDER: S-EPMC8343071 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The early detection of lung cancer continues to be a major clinical challenge. Using whole-transcriptome next-generation sequencing to analyze lung tumor and the matched noncancerous tissues, we previously identified 54 lung cancer-associated microRNAs (miRNAs). The objective of this study was to investigate whether the miRNAs could be used as plasma biomarkers for lung cancer. We determined expressions of the lung tumor-miRNAs in plasma of a development cohort of 180 subjects by using reverse transcription PCR to develop biomarkers. The development cohort included 92 lung cancer patients and 88 cancer-free smokers. We validated the biomarkers in a validation cohort of 64 individuals comprising 34 lung cancer patients and 30 cancer-free smokers. Of the 54 miRNAs, 30 displayed a significant different expression level in plasma of the lung cancer patients vs. cancer-free controls (all P < 0.05). A plasma miRNA signature (miRs-126, 145, 210, and 205-5p) with the best prediction was developed, producing 91.5% sensitivity and 96.2% specificity for lung cancer detection. Diagnostic performance of the plasma miRNA signature had no association with stage and histological type of lung tumor, and patients' age, sex, and ethnicity (all p > 0.05). The plasma miRNA signature was reproducibly confirmed in the validation cohort. The plasma miRNA signature may provide a blood-based assay for diagnosing lung cancer at the early stage, and thereby reduce the associated mortality and cost.
| S-EPMC5762367 | biostudies-literature
Project description:Bladder cancer is the 9th leading cause of cancer death worldwide. The major problem in bladder cancer is primarily the high recurrence rate after drug treatment and resection. Although conventional screening methods, such as cystoscopy, urinary cytology and ultrasound sonography, have become widely used in clinical settings, the diagnostic performance of these modalities is unsatisfactory due to low accuracy or high invasiveness. Because circulating micro RNA (miRNA) profiles have recently been reported as an attractive tool for liquid biopsy in cancer screening, here, we performed global miRNA profiling of 392 serum samples of bladder cancer patients with 100 non-cancer samples and 480 samples of other types of cancer as controls. We randomly classified the bladder cancer and control samples into 2 cohorts, a training set (N = 486) and a validation set (N = 486). By comparing both controls, we identified specific miRNA, such as miR-6087, for diagnosing bladder cancer in the training and validation sets. Furthermore, we found that a combination of 7 miRNA (7-miRNA panel: miR-6087, miR-6724-5p, miR-3960, miR-1343-5p, miR-1185-1-3p, miR-6831-5p and miR-4695-5p) could discriminate bladder cancer from non-cancer and other types of tumors with the highest accuracy (AUC: .97; sensitivity: 95%; specificity: 87%). The diagnostic accuracy was high, regardless of the stage and grade of bladder cancer. Our data demonstrated that the 7-miRNA panel could be a biomarker for the specific and early detection of bladder cancer.
| S-EPMC6317958 | biostudies-literature
Project description:A serum miRNA combination could be a powerful classifier for the detection of patients with bladder cancer.
2018-11-06 | GSE113486 | GEO
Project description:Esophageal cancer is one of the deadliest cancers worldwide. It typically has a poor overall prognosis because of diagnosis in advanced stages. Sensitive biomarkers for the early detection of esophageal cancer are urgently needed to reduce the high mortality of this disease. Circulating microRNAs (miRNAs) are emerging as a novel non-invasive biomarker for cancer diagnosis due to its high stability and specificity. In this study, we profiled circulating miRNAs in serum of patients with esophageal adenocarcinoma (EAC) using the Solexa sequencing analysis. The analysis demonstrated marked differences of more than 195 circulating miRNAs including 96 of upregulated and 99 of downregulated miRNA in EAC patients compared with healthy subjects. Quantitative reverse transcription PCR verified that the concentrations of circulating miR-25-3p and miR-151a-3p were significantly elevated, while the concentrations of miR-100-5p and miR-375 were significantly decreased in EAC patients compared with healthy controls. These data indicate the profile of these 4 miRNAs may potentially serve as a serum biomarker to identify patients with EAC, and circulating miRNA profiling may be clinically useful for early detection or treatment response in EAC patients.
| S-EPMC5126285 | biostudies-literature
Project description:ObjectivesPancreatic ductal adenocarcinoma (PDAC) presents the lowest survival rate of all cancers because only 6% of patients reach five-year survival. Alterations in the expression of several microRNAs (miRNAs) occur in the tumor of PDAC and in preneoplastic lesions as the called intraductal papillary mucinous neoplasm (IPMN). Here, we aimed at identifying which miRNAs are significantly altered in liquid biopsies from patients with PDAC and IPMN to find new noninvasive biomarkers for early detection of PDAC.MethodsWe analyzed by real-time quantitative reverse transcription-PCR (qRT-PCR) the expression of 17 circulating miRNAs, previously found to be significantly overexpressed in tissue pancreatic neoplasms, in a set of 182 plasma samples (94 PDAC, 19 IPMN, 18 chronic pancreatitis, and 51 disease-free controls). Then, we analyzed CA19.9 levels in the same plasma set, and we assessed the diagnostic values of differentially expressed miRNAs, CA19.9, and all possible combinations.ResultsOf note, 16, 14, and 9 miRNAs were significantly increased in PDAC, IPMN, and chronic pancreatitis, respectively, compared with control plasmas. miR-21-5p, miR-33a-3p, miR-320a, and miR-93-5p showed the highest discriminating capacity for pancreatic neoplasia (PDAC or IPMN) with an area under the receiver operating characteristic curve (AUC) of 0.86, 0.85, 0.85, and 0.80, respectively. 2-miRNA combinations improved these performances reaching AUC = 0.90 for "miR-33a-3p+miR-320a." Addition of CA19.9 increased the diagnostic potential of miRNA signatures even further achieving an AUC of 0.95 (93% sensitivity and 85% specificity) for the combination of "miR-33a-3p+miR-320a+CA19.9."ConclusionsNovel signatures combining miRNAs and CA19.9 could be used as noninvasive biomarkers for early detection of PDAC.
| S-EPMC6602779 | biostudies-literature
Project description:We previously developed three microRNAs (miRs-21, 210, and 486-5p), two long noncoding RNAs (lncRNAs) (SNHG1 and RMRP), and two fucosyltransferase (FUT) genes (FUT8 and POFUT1) as potential plasma biomarkers for lung cancer. However, the diagnostic performance of the individual panels is not sufficient to be used in the clinics. Given the heterogeneity of lung tumors developed from multifactorial molecular aberrations, we determine whether integrating the different classes of molecular biomarkers can improve diagnosis of lung cancer. By using droplet digital PCR, we analyze expression of the seven genes in plasma of a development cohort of 64 lung cancer patients and 33 cancer-free individuals. The panels of three miRNAs (miRs-21, 210, and 486-5p), two lncRNAs (SNHG1 and RMRP), and two FUTs (FUT8 and POFUT1) have a sensitivity of 81-86% and a specificity of 84-87% for diagnosis of lung cancer. From the seven genes, an integromic plasma signature comprising miR-210, SNHG1, and FUT8 is developed that produces higher sensitivity (95.45%) and specificity (96.97%) compared with the individual biomarker panels (all p<0.05). The diagnostic value of the signature was confirmed in a validation cohort of 40 lung cancer patients and 29 controls, independent of stage and histological type of lung tumor, and patients' age, sex, and smoking status (all p>0.05). The integration of the different categories of biomarkers might improve diagnosis of lung cancer.
| S-EPMC5973873 | biostudies-other
Project description:INTRODUCTION: MicroRNAs (miRNAs, miRs) are a class of small, non-coding RNA molecules with relevance as regulators of gene expression thereby affecting crucial processes in cancer development. MiRNAs offer great potential as biomarkers for cancer detection due to their remarkable stability in blood and their characteristic expression in many different diseases. We investigated whether microarray-based miRNA profiling on whole blood could discriminate between early stage breast cancer patients and healthy controls. METHODS: We performed microarray-based miRNA profiling on whole blood of 48 early stage breast cancer patients at diagnosis along with 57 healthy individuals as controls. This was followed by a real-time semi-quantitative Polymerase Chain Reaction (RT-qPCR) validation in a separate cohort of 24 early stage breast cancer patients from a breast cancer screening unit and 24 age matched controls using two differentially expressed miRNAs (miR-202, miR-718). RESULTS: Using the significance level of p<0.05, we found that 59 miRNAs were differentially expressed in whole blood of early stage breast cancer patients compared to healthy controls. 13 significantly up-regulated miRNAs and 46 significantly down-regulated miRNAs in our microarray panel of 1100 miRNAs and miRNA star sequences could be detected. A set of 240 miRNAs that was evaluated by radial basis function kernel support vector machines and 10-fold cross validation yielded a specificity of 78.8%, and a sensitivity of 92.5%, as well as an accuracy of 85.6%. Two miRNAs were validated by RT-qPCR in an independent cohort. The relative fold changes of the RT-qPCR validation were in line with the microarray data for both miRNAs, and statistically significant differences in miRNA-expression were found for miR-202. CONCLUSIONS: MiRNA profiling in whole blood has potential as a novel method for early stage breast cancer detection, but there are still challenges that need to be addressed to establish these new biomarkers in clinical use.
| S-EPMC3252341 | biostudies-literature
Project description:BackgroundAcute kidney injury (AKI) is a common complication of acute myocardial infarction (AMI), and is associated with adverse outcomes. The study aimed to identify a miRNA signature for the early diagnosis of post-AMI AKI.MethodsA total of 108 patients admitted to a coronary care unit (CCU) were divided into four subgroups: AMI-AKI-, AMI+AKI-, AMI+AKI+, and AMI-AKI+. Thirty-six miRNA candidates were selected based on an extensive literature review. Real-time quantitative RT-PCR analysis was used to determine the expression levels of these miRNAs in the serum collected on the day of CCU admittance. TargetScan 7.1 and miRDB databases were used for target prediction and Metacore 6.13 was used for pathway analysis.ResultsThrough a stepwise selection based on abundance, hemolytic effect and differential expression between four groups, 9 miRNAs were found to have significantly differential expression levels as potential biomarkers for post-AMI AKI specifically. Noticeably, the expression levels of miR-24, miR-23a and miR-145 were significantly down-regulated in AMI+AKI+ patients compared to those in AMI+AKI- patients. Combination of the three miRNAs as a panel showed the best performance in the early detection of AKI following AMI (AUC = 0.853, sensitivity 95.65%), compared to the analysis of serum neutrophil gelatinase-associated lipocalin (AUC = 0.735, sensitivity 63.16%). Furthermore, bioinformatic analysis indicated that these three miRNAs regulate the transforming growth factor beta signaling pathway and involve in apoptosis and fibrosis in AKI.ConclusionsFor the first time, this study identify a unique circulating miRNA signature (miR-24-3p, miR-23a-3p, miR-145-5p) that can potentially early detect AKI following AMI and may be involved in renal injury and fibrosis in post-AMI AKI pathogenesis.
| S-EPMC6492315 | biostudies-literature
Project description:We describe a new signature definition and analysis method to be used as biomarker for early cancer detection. Our new approach is based on the construction of a reference map of transcriptional signatures of both healthy and cancer affected individuals using circulating miRNA from a large number of subjects. Once such a map is available, the diagnosis for a new patient can be performed by observing the relative position on the map of his/her transcriptional signature. To demonstrate its efficacy for this specific application we report the results of the application of our method to published datasets of circulating miRNA, and we quantify its performance compared to current state-of-the-art methods. A number of additional features make this method an ideal candidate for large-scale use, for example, as a mass screening tool for early cancer detection or for at-home diagnostics. Specifically, our method is minimally invasive (because it works well with circulating miRNA), it is robust with respect to lab-to-lab protocol variability and batch effects (it requires that only the relative ranking of expression value of miRNA in a profile be accurate not their absolute values), and it is scalable to a large number of subjects. Finally we discuss the need for HPC capability in a widespread application of our or similar methods.
| S-EPMC4087284 | biostudies-literature
Project description:Patients with locally advanced rectal cancer (LARC) are recommended to receive preoperative chemoradiotherapy (PCRT) followed by surgery. Response to PCRT varies widely: 60%-70% of patients with LARC do not derive therapeutic benefit from PCRT, whereas 15%-20% of patients achieve pathologic complete response (pCR). We sought to develop a liquid biopsy assay for identifying response to PCRT in patients with LARC. MATERIALS AND METHODS:We analyzed two genome-wide microRNA (miRNA) expression profiling data sets from tumor tissue samples for in silico discovery (GSE68204) and validation (GSE29298). We prioritized biomarkers in pretreatment plasma specimens from clinical training (n = 41; 15 responders and 26 nonresponders) and validation (n = 65; 29 responders and 36 nonresponders) cohorts of patients with LARC. We developed an integrated miRNA panel and established a risk assessment model, which was combined with the miRNA panel and carcinoembryonic antigen levels. RESULTS:Our comprehensive discovery effort identified an 8-miRNA panel that robustly predicted response to PCRT, with an excellent accuracy in the discovery (area under the curve [AUC] = 0.95) and validation (AUC = 0.92) cohorts. We successfully established a circulating miRNA panel with remarkable diagnostic accuracy in the clinical training (AUC = 0.82) and validation (AUC = 0.81) cohorts. Moreover, the predictive accuracy of the panel was significantly superior to conventional clinical factors in both cohorts (P < .01) and the risk assessment model was superior (AUC = 0.83). Finally, we applied our model to detect patients with pathologic complete response and showed that it was dramatically superior to currently used pathologic features (AUC = 0.92). CONCLUSION:Our novel risk assessment signature for predicting response to PCRT has a potential for clinical translation as a liquid biopsy assay in patients with LARC.
| S-EPMC8668014 | biostudies-literature