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BACKGROUND & AIMS: Early-onset colorectal cancer (EOCRC) is a distinct clinical and molecular entity with poor survival outcomes compared with late-onset CRC. Although the incidence of EOCRC is rising, current CRC screening strategies have several limitations in diagnostic performance for EOCRC. In view of this clinical challenge, novel and robust biomarkers for detection of EOCRC are necessary. The aim of this study was to develop a circulating micro RNA (miRNA) signature for the diagnosis of patients with EOCRC. METHODS: A systematic discovery approach by analyzing a large, publicly available, noncoding RNA expression profiling dataset (GSE115513) was used. A panel of miRNAs was identified, which was subsequently validated in blood samples from patients with EOCRC in 2 independent cohorts (n = 149) compared with controls (n = 110) and pre/postoperative plasma specimens (n = 22) using quantitative reverse-transcription polymerase chain reaction assays. RESULTS: In the discovery phase, 4 miRNAs were found to be expressed in blood samples. A combination signature of these 4 miRNAs (miR-193a-5p, miR-210, miR-513a-5p, and miR-628-3p) yielded an area under the curve of 0.92 (95% confidence interval, 0.85-0.96) for identification of EOCRC in the training cohort. The miRNA panel performance was then confirmed in an independent validation cohort (area under the curve, 0.88; 95% confidence interval, 0.82-0.93). Moreover, the miRNA panel robustly identified patients with early-stage EOCRC (P < .001). The decreased expression of miRNAs in postsurgery plasma specimens indicated their tumor specificity. CONCLUSIONS: Our novel miRNA signature for the diagnosis of EOCRC has the potential to identify patients with EOCRC with high accuracy for clinical application in the noninvasive diagnosis of EOCRC.

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BACKGROUND: Liquid biopsy is a rapidly growing field, for it may provide a minimally invasive way to acquire pathological data for personalized medicine. This study developed a systemic strategy to discover an effective salivary biomarker for early detection of patients with head-neck squamous carcinoma (HNSC) and oral precancer lesion (OPC). METHODS: A total of 10 miRNAs were examined in parallel with multiple independent cohorts. These included a training set of salivary samples from HNSC patients, the TCGA-HNSC and GSE31277 cohorts to differentiate miRNAs between tumor and normal tissues, and groups of salivary samples from healthy individuals, patients with HNSC and OPC. RESULTS: The combined results from the salivary training set and the TCGA-HNSC cohort showed that four miRNAs (miR-148b, miR-155, miR-196b, and miR-31) consistently increased in HNSC patients. Further integration with the GSE31277 cohort, two miRNAs (miR-31 and miR-196b) maintained at high significances. Further assessment showed that salivary miR-196b was a prominent diagnostic biomarker, as it remarkably discriminated between healthy individuals and patients with HNSC (p < 0.0001, AUC = 0.767, OR = 5.64) or OPC (p < 0.0001, AUC = 0.979, OR = 459). CONCLUSION: Salivary miR-196b could be an excellent biomarker for diagnosing OPC and early detection of HNSC. This molecule may be used for early screening high-risk groups of HNSC.

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BACKGROUND: MicroRNAs(miRNAs) are involved in the formation, maintenance, and metastasis of urologic cancer. Here, we aim to gather and evaluate all of the evidence regarding the potential role of miRNAs as novel predictors of urologic cancer survival. METHODS: A systematic review was performed to identify and score all of the published studies that evaluated the prognostic effects of miRNAs in kidney (KCa), bladder (BCa) or prostate cancer (PCa). Where appropriate, the summary effects of miRNAs on urologic cancer were meta-analysed. The reliability of those results was then further validated by an integrated analysis of the TCGA cohort and miRNA panel. RESULTS: Of 151 datasets, 80 miRNAs were enrolled in this systematic review. A meta-analysis of the prognostic qualities of each miRNA identified an objective association between miRNA and prognosis. miR-21 was identified as an unfavourable miRNA with the overall survival (HR:2.699, 1.76-4.14, P < 0.001) across various prognostic events. Our further meta-analyses, integrating a parallel TCGA analysis, confirmed these partial previous results and further revealed different summary effects, such as the moderate effect of miR-21 in BCa. The refined miRNA panel (KCa-6: miR-27b, -942, -497, -144, -141 and -27a) was more capable of predicting the overall survival than was any single miRNAs included in it (HR: 3.214, 1.971-5.240, P < 0.01). CONCLUSIONS: A miRNA panel may be able to determine the prognosis of urologic tumour more effectively and compensate for the unreliability of individual miRNA in estimating prognosis. More large-scale studies are therefore required to evaluate the unbiased prognostic value of miRNAs in urologic cancer effectively.

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AIM: To evaluate the diagnostic potential of a six microRNAs (miRNAs) panel consisting of miR-21, miR-144, miR-107, miR-342, miR-93 and miR-152 for esophageal cancer (EC) detection. METHODS: The expression of miRNAs was analyzed in EC sera samples using quantitative real-time PCR. Risk score analysis was performed and linear regression models were then fitted to generate the six-miRNA panel. In addition, we made an effort to identify significantly dysregulated miRNAs and mRNAs in EC using the Cancer Genome Atlas (TCGA) miRNAseq and RNAseq datasets, respectively. Further, we identified significantly correlated miRNA-mRNA target pairs by integrating TCGA EC miRNAseq dataset with RNAseq dataset. RESULTS: The panel of circulating miRNAs showed enhanced sensitivity (87.5%) and specificity (90.48%) in terms of discriminating EC patients from normal subjects (area under the curve [AUC] = 0.968). Pathway enrichment analysis for potential targets of six miRNAs revealed 48 significant (P < 0.05) pathways, viz. pathways in cancer, mRNA surveillance, MAPK, Wnt, mTOR signaling, and so on. The expression data for mRNAs and miRNAs, downloaded from TCGA database, lead to identification of 2309 differentially expressed genes and 189 miRNAs. Gene ontology and pathway enrichment analysis showed that cell-cycle processes were most significantly enriched for differentially expressed mRNA. Integrated analysis of TCGA miRNAseq and RNAseq datasets resulted in identification of 53 063 significantly and negatively correlated miRNA-mRNA pairs. CONCLUSION: In summary, a novel and highly sensitive signature of serum miRNAs was identified for EC detection. Moreover, this is the first report identifying miRNA-mRNA target pairs from EC TCGA dataset, thus providing a comprehensive resource for understanding the interactions existing between miRNA and their target mRNAs in EC.

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Lung cancer is the most common cause of cancer deaths all over the world, in which non-small cell lung cancer (NSCLC) accounts for ~85% of cases. It is well known that microRNAs (miRNAs) play a critical role in various cellular processes, mediating post-transcriptional silencing either by mRNA degradation through binding the 3' UTR of target mRNA or by translational inhibition of the protein. In the past decade, miRNAs have also been increasingly identified in biological fluids such as human serum or plasma known as circulating or cell-free miRNAs, and may function as non-invasive diagnostic markers for various cancer types including NSCLC. Circulating tumor cells (CTCs) are those cells that are shed from solid tumors and then migrate into the circulation. However, reports concerning the roles of CTCs are quite rare, which may be attributed to the difficulties in the enrichment and detection of CTCs in the circulation. Although, there have been reassuring advances in identifying circulating miRNA-panels, which are assumed to be of diagnostic value in NSCLC early stage, some issues remain concerning the reliability of using miRNA panels as a diagnostic tool for NSCLC. In the current review, we are aiming at providing insights into the miRNAs biology, the mechanisms of miRNAs release into the bloodstream, cell-free miRNAs as the diagnostic markers for NSCLC and the current limitations of CTCs as diagnostic markers in NSCLC.