• Lung adenocarcinoma
• RBM10
• miR-224-5p
• p53

• CRISPR/Cas13a
• DNAzyme
• Electrochemiluminescence biosensor
• Magnetic electrochemiluminescence nanoparticle
• miRNA

• Luminescent Measurements
• DNA, Catalytic
• Reproducibility of Results
• Metal Nanoparticles
• Biosensing Techniques
• DNA
• MicroRNAs
• Magnetic Phenomena
• Electrochemical Techniques
• Metallocenes
• Ferrous Compounds

• Biomarkers
• diagnostic odds ratio
• lung cancer
• metabolites
• micro-RNA
• sensitivity
• specificity

• Humans
• MicroRNAs/genetics
• Lung Neoplasms/diagnosis
• Lung Neoplasms/genetics
• Prospective Studies
• Biomarkers
• Biopsy
• Biomarkers, Tumor/genetics

• Benign and malignant
• Circulating miRNA
• Diagnosis
• Meta-analysis
• Pulmonary nodules

• Humans
• MicroRNAs
• Databases, Factual
• ROC Curve
• Software

• Humans
• Female
• MicroRNAs
• Carcinoma, Hepatocellular
• Prognosis
• Carcinoma, Squamous Cell
• Mouth Neoplasms
• Pancreatic Neoplasms
• Lung Neoplasms
• Breast Neoplasms
• Leukemia
• Liver Neoplasms
• Biomarkers, Tumor/metabolism

• early detection
• lung cancer
• microRNA
• protein biomarkers

• U01 CA086368 NCI NIH HHS
• U01 CA167462 NCI NIH HHS
• U01 CA213285 NCI NIH HHS
• U24 CA086368 NCI NIH HHS

• Diagnosis
• MicroRNA-21
• Prognosis
• meta analysis

• Biomarkers, Tumor/genetics
• Biomarkers, Tumor/metabolism
• Humans
• Lung Neoplasms/diagnosis
• Lung Neoplasms/genetics
• MicroRNAs/genetics
• MicroRNAs/metabolism
• Prognosis
• Proportional Hazards Models

• Lung cancer
• NSCLC
• diagnostic biomarker
• early diagnosis
• microRNA

• Area Under Curve
• Biomarkers, Tumor/genetics
• Carcinoma, Non-Small-Cell Lung/diagnosis
• Carcinoma, Non-Small-Cell Lung/genetics
• Humans
• Lung Neoplasms/diagnosis
• Lung Neoplasms/genetics
• MicroRNAs/metabolism

To investigate the diagnostic performance of microRNA‐21 detected in serum or sputum as a biomarker for lung carcinoma identification through pooling the open published data.

Clinical diagnostic studies related to microRNA‐21 as a biomarker for lung carcinoma identification were electronically searched in the databases of Pubmed, EMBASE, Cochrane Library, Chinese National Knowledge Infrastructure, Wanfang, and Google Scholar. The data of the included studies was extracted and made pooling of diagnostic sensitivity, specificity, diagnostic odds ratio (DOR), area under the summary receiver operating characteristic curve (ROC) (AUC) for microRNA‐21 expression in serum or sputum as a biomarker for lung carcinoma identification. The publication bias was evaluated by Deek's funnel plot.

Seventeen diagnostic studies were finally included and made data pooling. For the included 17 studies, 4 investigated the microRNA‐21 expression in sputum and 13 studies in serum. The pooled diagnostic sensitivity and specificity were 0.73 (95% CI, 0.67–0.78) and 0.81 (95% CI, 0.75–0.85), respectively, under random effect model. The combined DOR was 9.65 (95% CI, 6.64–14.03) with the AUC of 0.84 (95% CI, 0.80–0.87). Given a pre‐test probability of 50%, the post‐test positive probability and post‐test negative probability were 79% and 25%, respectively, by using microRNA‐21 as a biomarker for lung carcinoma diagnosis. Deek's funnel was obviously asymmetry and indicated significant publication bias (p < 0.05).

MicroRNA‐21 in serum or sputum was a promising biomarker for lung cancer identification with relative high diagnostic sensitivity and specificity.

• biomarker
• diagnosis
• lung carcinoma
• meta-analysis
• microRNA-21

• Lung cancer
• adenocarcinoma
• cancer biomarker
• carboxypeptidase E

Early identification of epidermal growth factor receptor (EGFR) and Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations is crucial for selecting a therapeutic strategy for patients with non-small-cell lung cancer (NSCLC). We proposed a machine learning-based model for feature selection and prediction of EGFR and KRAS mutations in patients with NSCLC by including the least number of the most semantic radiomics features. We included a cohort of 161 patients from 211 patients with NSCLC from The Cancer Imaging Archive (TCIA) and analyzed 161 low-dose computed tomography (LDCT) images for detecting EGFR and KRAS mutations. A total of 851 radiomics features, which were classified into 9 categories, were obtained through manual segmentation and radiomics feature extraction from LDCT. We evaluated our models using a validation set consisting of 18 patients derived from the same TCIA dataset. The results showed that the genetic algorithm plus XGBoost classifier exhibited the most favorable performance, with an accuracy of 0.836 and 0.86 for detecting EGFR and KRAS mutations, respectively. We demonstrated that a noninvasive machine learning-based model including the least number of the most semantic radiomics signatures could robustly predict EGFR and KRAS mutations in patients with NSCLC.

• EGFR mutation
• KRAS mutation
• eXtreme Gradient Boosting
• feature selection
• genetic algorithm
• low-dose computed tomography
• machine learning
• non-small-cell lung carcinoma
• radiogenomics

• Aged
• Aged, 80 and over
• Algorithms
• Biomarkers
• Carcinoma, Non-Small-Cell Lung/diagnostic imaging
• Carcinoma, Non-Small-Cell Lung/genetics
• Carcinoma, Non-Small-Cell Lung/pathology
• ErbB Receptors/genetics
• Female
• Humans
• Lung Neoplasms/diagnostic imaging
• Lung Neoplasms/genetics
• Lung Neoplasms/pathology
• Machine Learning
• Male
• Middle Aged
• Mutation
• Neoplasm Staging
• Proto-Oncogene Proteins p21(ras)/genetics
• ROC Curve
• Reproducibility of Results
• Supervised Machine Learning
• Tomography, X-Ray Computed

Circulating miRNAs are ideal diagnostics and prognostics biomarkers in cancer since altered levels of specific miRNAs have been associated to development/progression of several cancers. Physical activity is a recognized preventive strategy against several cancers, but it may also modify the baseline levels of cancer-associated miRNAs and, hence, may act as a confounding pre-analytical variable. This study aimed at understanding whether physical activity-dependent changes in cancer-associated circulating miRNAs profile could act as a confounding variable. A panel comprising 179 miRNAs was assayed in plasma from 20 highly trained and 10 sedentary men. RT-qPCR data were analyzed with the 2^−2ΔΔCT methods and normalized on hsa-miR-320d, as determined by bioinformatics analysis. miRNAs associated with the diagnosis of the most prevalent cancers were considered. Only those miRNAs, relevantly associated with cancers, found ≥2-fold up- or downregulated in highly trained subjects compared to sedentary were disclosed. The results reveal that chronic physical activity determined modifications altering the baseline level of several cancer-associated miRNAs and, hence, their diagnostic and prognostic potential. In conclusion, based on our results, a physically active status emerges as an important pre-analytical variable able to alter the basal level of circulating miRNAs, and these alterations might be considered as potentially misleading the analytical output.

• cancer biomarkers
• circulating miRNAs
• physical activity
• pre-analytical variables

• Epithelial ovarian cancer
• Exosomal miRNA profiling
• Exosomes
• miR-4732-5p
• microRNAs

• Adult
• Aged
• Biomarkers, Tumor/metabolism
• Carcinoma, Ovarian Epithelial/diagnosis
• Carcinoma, Ovarian Epithelial/genetics
• Exosomes/metabolism
• Female
• Humans
• MicroRNAs/metabolism
• Middle Aged

• 2016R1D1A1B04932862 National Research Foundation of Korea
• 2018M3A9E8021512 National Research Foundation of Korea

• MiR-21
• PI3K/AKT signal pathway
• acute lung injury
• asthma
• idiopathic pulmonary fibrosis
• lung cancer

• AD = adenocarcinoma
• AUC-ROC curve = area under the receiver operating characteristics curve
• BSC = best supportive care
• CEA = carcinoembryonic antigen
• CYFRA21-1 = cytokeratin 19 fragment 21-1
• ICIs = immune checkpoint inhibitors
• LCC = large cell carcinoma
• LC = lung cancer
• LDCT = low-dose CT
• NSCLC = non–small cell lung cancer
• PBMC = peripheral blood mononuclear cell
• PD-1 = programmed cell death-1
• PD-L1 = programmed cell death-ligand 1
• PET = positron emission tomography
• PNs = pulmonary nodules
• SCC = squamous cell carcinoma antigen
• SCLC = small cell lung cancer
• SQ = squamous cell carcinoma
• TMB = tumor mutation burden
• ddPCR = droplet digital PCR

• biomarkers
• exosome
• extracellular vesicles
• lung cancer
• miRNA
• plasma
• serum

The prognosis of lung cancer patients with different clinical stages is significantly different. The 5-year survival of stage IA groups can exceed 90%, while patients with stage IV can be less than 10%. Therefore, early diagnosis is extremely important for lung cancer patients. This research focused on various diagnosis methods of early lung cancer, including imaging screening, bronchoscopy, and emerging potential liquid biopsies, as well as volatile organic compounds, autoantibodies, aiming to improve the early diagnosis rate and explore feasible and effective early diagnosis strategies.

• LDCT
• bronchoscopy
• diagnosis
• liquid biopsy
• lung cancer

• Pdcd4
• Reck
• asbestos
• cancer
• lung
• microRNA

• Animals
• Apoptosis Regulatory Proteins/genetics
• Asbestos/toxicity
• Asbestos, Crocidolite/administration & dosage
• Asbestos, Serpentine/administration & dosage
• Disease Models, Animal
• Down-Regulation
• GPI-Linked Proteins/genetics
• Gene Expression/drug effects
• Lung/pathology
• Male
• Mice
• Mice, Inbred ICR
• MicroRNAs/genetics
• Microarray Analysis
• RNA-Binding Proteins/genetics
• Up-Regulation

• 23659328 Ministry of Education, Culture, Sports, Science and Technology, Japan
• 24390153 Ministry of Education, Culture, Sports, Science and Technology, Japan
• 15H04784 Ministry of Education, Culture, Sports, Science and Technology, Japan
• 18H03038 Ministry of Education, Culture, Sports, Science and Technology, Japan
• Grants-in-Aid for Scientific Research

• NSCLC
• diagnostic test
• meta-analysis
• miR-145

• Biomarkers
• early detection
• miR-21
• miR-23a
• non-small-cell lung cancer
• tumor.

• Indeterminate pulmonary nodules (IPNs)
• biomarkers
• management
• prediction

• Exosomes
• Intercellular communication
• MicroRNAs

Commonly used miRNA detection methods cannot be applied for high-throughput analyses. However, this study was aimed to performed a liquid bead array detection system (LBAS) to detect tissue 6 miRNAs in non-small cell lung cancer (NSCLC).

In this study, evaluation of LBAS was performed to observe the precision, specificity, limitation and stability. Then, a total of 52 primary NSCLC patients who received resection operation without preoperative radiotherapy and chemotherapy between June 2013 and March 2014 were selected, and then the total RNA of the tissues were extracted. We prepared six NSCLC-related miRNAs for LBAS. After optimization and evaluation, LBAS was verified by detecting the relative expression levels of 6 microRNAs in the pathological tissues and corresponding normal tissues of 52 NSCLC patients.

The results of evaluation of LBAS showed that the Mean Fluorescence Intensity (MFI) of the reaction only added with chimeric probes and beads showed no significant change after 180 days (P > 0.05). And the intra-assay Coefficient of Variation (CV) was between 1.57 and 3.5%, while the inter-assay CV was between 4.24 and 11.27%, indicating this system was ideal for diagnostic reagents. In addition, only the beads corresponding to the additional miRNAs showed high MFIs from 8426 to 18,769, whereas the fluorescence values of the other beads were under background levels (MFIs = 20 to 55) in each reaction, indicating no cross reactivity among the miRNAs. The limit of detection of miR-21, miR-210, miR-125b, miR-155, miR-375, and miR-31 were 5.27, 1.39, 1.85, 2.01, 1.34, and 2.73 amol/μL, respectively, showing that the lowest detection limit of miRNA by this system was under pM level. Then, the relative expression levels of miR-21, miR-210, miR-125b, miR-155, miR-375, and miR-31 by using this system were significantly correlated with NSCLC (P < 0.05). And the results of AUC method indicated that specific of the LBAS system was 94.2%.

Our findings suggest that LBAS was simple, high-throughput, and freely combined with absolute quantification. Thus, this system could be applied for tumor miRNAs detection.

• Liquid bead array
• Lung cancer
• Tumor tissue
• miRNAs

• Biomarker
• Diagnosis
• Lung cancer
• Prognosis
• miR-155

• Biomarkers, Tumor/genetics
• Disease-Free Survival
• Gene Expression Regulation, Neoplastic
• Humans
• Lung Neoplasms/genetics
• Lung Neoplasms/pathology
• MicroRNAs/genetics
• Prognosis

• 81874230 the Natural Science Foundation of China

• biomarkers
• breast cancer
• circulating miRNAs
• extraanalytical variability, sensitivity and specificity
• lung cancer
• miRNA signature
• osteosarcoma
• prostate cancer

• Lung cancer (LC)
• diagnosis
• microRNA (miRNA)
• serum

• P30 CA046592 NCI NIH HHS
• R01 CA154365 NCI NIH HHS
• R21 CA205414 NCI NIH HHS
• U01 CA157715 NCI NIH HHS

• Biomarker
• Early diagnosis
• Hepatocellular carcinoma
• microRNAs

Early diagnosis of colon cancer (CC) is clinically important, as it can significantly improve patients’ survival rate and quality of life. Although the potential role for small extracellular vesicles (sEVs) in early detection of many diseases has been repeatedly mentioned, systematic screening of plasma sEVs derived early CC specific biomarkers has not yet been reported. In this work, plasma sEVs enriched fractions were derived from 15 early-stage (TisN0M0) CC patients and 10 normal controls (NC). RNA sequencing identified a total number of 95 sEVs enriched fraction derived miRNAs with differential expression between CC and NC, most of which (60/95) was in well accordance with tissue results in the Cancer Genome Atlas (TCGA) dataset. Among those miRNAs, we selected let-7b-3p, miR-139-3p, miR-145-3p, and miR-150-3p for further validation in an independent cohort consisting of 134 participants (58 CC and 76 NC). In the validation cohort, the AUC of 4 individual miRNAs ranged from 0.680 to 0.792. A logistic model combining two miRNAs (i.e. let-7b-3p and miR-145-3p) achieved an AUC of 0.901. Adding the 3rd miRNA into this model can further increase the AUC to 0.927. Side by side comparison revealed that sEVs miRNA profile outperformed cell-free plasma miRNA in the diagnosis of early CC. In conclusion, we suggested that circulating sEVs enriched fractions have a distinct miRNA profile in CC patients, and sEVs derived miRNA could be used as a promising biomarker to detect CC at an early stage.

• Extracellular vesicles
• biomarker
• early colon cancer
• miRNAs

• AUC
• diagnosis
• lung neoplasms
• microRNAs
• sensitivity and specificity

• Prostate cancer (PCa)
• epithelial-mesenchymal transition (EMT)
• miR-200c-3p/ZEB2 loop
• tumor progression

• East Asian populations
• early detection
• lung cancer
• miRNA

In recent years, with the increase in cancer mortality caused by metastasis, and with the development of individualized and precise medical treatment, early diagnosis with precision becomes the key to decrease the death rate. Since detecting tumour biomarkers in body fluids is the most non‐invasive way to identify the status of tumour development, it has been widely investigated for the usage in clinic. These biomarkers include different expression or mutation in microRNAs (miRNAs), circulating tumour DNAs (ctDNAs), proteins, exosomes and circulating tumour cells (CTCs). In the present article, we summarized and discussed some updated research on these biomarkers. We overviewed their biological functions and evaluated their multiple roles in human and small animal clinical treatment, including diagnosis of cancers, classification of cancers, prognostic and predictive values for therapy response, monitors for therapy efficacy, and anti‐cancer therapeutics. Biomarkers including different expression or mutation in miRNAs, ctDNAs, proteins, exosomes and CTCs provide more choice for early diagnosis of tumour detection at early stage before metastasis. Combination detection of these tumour biomarkers may provide higher accuracy at the lowest molecule combination number for tumour early detection. Moreover, tumour biomarkers can provide valuable suggestions for clinical anti‐cancer treatment and execute monitoring of treatment efficiency.

• CTCs
• ctDNAs
• exosomes
• miRNAs
• proteins
• tumour biomarkers

• Fine-needle aspirates
• Pancreatic cancer
• Prostate cancer
• Serum
• miRNAs

• circulating miRNAs
• circulating nucleic acids
• environmental health
• lung cancer
• nanobiosensor
• quantum dots
• translational medicine
• translational research

• TaqMan
• biomarkers
• circulating microRNAs
• resection
• reverse transcription-quantitative polymerase chain reaction

(1) Background. Non-small cell lung cancer (NSCLC) has a high mortality rate. MiRNAs have been found to be diagnostic biomarkers for NSCLC. However, controversial results exist. We conducted this meta-analysis to evaluate the diagnostic value of miRNAs for NSCLC. (2) Methods. Databases and reference lists were searched. Pooled sensitivity (SEN), specificity (SPE), and area under the curve (AUC) were applied to examine the general diagnostic efficacy, and subgroup analysis was also performed. (3) Results. Pooled SEN, SPE, and AUC were 85%, 88%, and 0.93, respectively, for 71 studies. Multiple miRNAs (AUC: 0.96) obtained higher diagnostic value than single miRNA (AUC: 0.86), and the same result was found for Caucasian population (AUC: 0.97) when compared with Asian (AUC: 0.91) and Caucasian/African population (AUC: 0.92). MiRNA had higher diagnostic efficacy when participants contained both smokers and nonsmokers (AUC is 0.95 for imbalanced group and 0.91 for balanced group) than when containing only smokers (AUC: 0.90). Meanwhile, AUC was 0.91 for both miR-21 and miR-210. (4) Conclusions. Multiple miRNAs such as miR-21 and miR-210 could be used as diagnostic tools for NSCLC, especially for the Caucasian and nonsmoking NSCLC.

• diagnosis
• metastasis
• microRNA-21
• non-small cell lung cancer
• prognosis

• Lung cancer
• early diagnosis
• lung nodule
• screening

MiR-21 has been identified as one of the most common proto-oncogenes. It is hypothesized that up-regulated miR-21 could be served as a potential biomarker for human cancer diagnosis. However, inconsistencies or discrepancies about diagnostic accuracy of circulating miR-21 still remain. In this sense, miR-21′s diagnostic value needs to be fully validated. In this study, we performed an update meta-analysis to estimate the diagnostic value of circulating miR-21 in various human cancers. Additionally, we conducted a validation test on 50 endometrial cancer patients, 50 benign lesion patients and 50 healthy controls. A systematical literature search for relevant articles was performed in Pubmed, Embase and Cochrane Library. A total of 48 studies from 39 articles, involving 3,568 cancer patients and 2,248 controls, were included in this meta-analysis. The overall sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR) and area under the curve (AUC) were 0.76 (0.71-0.80), 0.82 (0.79-0.85), 4.3 (3.6-5.1), 0.29 (0.24-0.35), 15 (11-20) and 0.86 (0.83-0.89), respectively. In the validation test, the expression levels of serum miR-21 were significantly higher in benign lesion patients (p = 0.003) and endometrial cancer patients (p = 0.000) compared with that of healthy controls. Endometrial cancer patients showed higher miR-21 expression levels (p = 0.000) compared with benign lesion patients. In conclusion, the meta-analysis shows that circulating miR-21 has excellent performance on the diagnosis for various cancers and the validation test demonstrates that serum miR-21 could be served as a novel biomarker for endometrial carcinoma.

• cancers
• diagnosis
• endometrial carcinoma
• meta-analysis
• miR-21

The subtypes of NSCLC have unique characteristics of pathogenic mechanism and responses to targeted therapies. Thus, non-invasive markers for diagnosis of different subtypes of NSCLC at early stage are needed.

Based on the results from the screening and validation process, 3 miRNAs (miR-532, miR-628-3p and miR-425-3p) were found to display significantly different expression levels in early-stage lung adenocarcinoma, as compared to those in healthy controls. ROC analysis showed that the miRNA–based biomarker could distinguish lung adenocarcinoma from healthy controls with high AUC (0.974), sensitivity (91.5%), and specificity (97.8%). Importantly, these three miRNAs could also distinguish lung adenocarcinoma from lung benigh diseases and other subtypes of lung cancer.

Two hundreds and one early-stage lung adenocarcinoma cases and one hundreds seventy eight age- and sex-matched healthy controls were recruited to this study. We screened the differentially expressed plasma miRNAs using TaqMan Low Density Arrays (TLDA) followed by three-phase qRT-PCR validation. A risk score model was established to evaluate the diagnostic value of the plasma miRNA profiling system.

Taken together, these findings suggest that the 3 miRNA–based biomarker might serve as a novel non-invasive approach for diagnosis of early-stage lung adenocarcinoma.

• biomarker
• diagnosis
• lung adenocarcinoma
• miRNA
• plasma

• Lung cancer
• Primary miRNA
• Squamous-cell carcinoma
• miRNA

Evidence is accumulating highlighting the importance of extracellular miRNA as a novel biomarker for diagnosing various kinds of malignancies. MiR-21 is one of the most studied miRNAs and is over-expressed in cancer tissues. To explore the clinical implications and secretory mechanisms of extracellular miR-21, we firstly meta-analyzed the diagnostic efficiency of extracellular miR-21 in different cancer types. Eighty-one studies based on 59 articles were finally included. In our study, extracellular miR-21 was observed to exhibit an outstanding diagnostic accuracy in detecting brain cancer (area under the summary receiver operating characteristic curve or AUC = 0.94), and this accuracy was more obvious in glioma diagnosis (AUC = 0.95). Our validation study (n = 45) further confirmed the diagnostic and prognostic role of miR-21 in cerebrospinal fluid (CSF) for glioma. These findings inspired us to explore the biological function of miR-21. We next conducted mechanistic investigations to explain the secretory mechanisms of extracellular miR-21 in glioma. TGF-β/Smad3 signaling was identified to participate in mediating the release of miR-21 from glioma cells. Further targeting TGF-β/Smad3 signaling using galunisertib, an inhibitor of the TGF-β type I receptor kinase, can attenuate the secretion of miR-21 from glioma cells. Taken together, CSF-based miR-21 might serve as a potential biomarker for diagnosing brain cancer, especially for patients with glioma. Moreover, extracellular levels of miR-21 were affected by exogenous TGF-β activity and galunisertib treatment.

• TGF-β/Smad3 signaling
• cerebrospinal fluid
• diagnosis
• extracellular miR-21
• glioma

Many studies have investigated the diagnostic role of circulating microRNAs (miRNAs) in patients with lung cancer; however, the results still remain inconclusive. An updated system review and meta-analysis was necessary to give a comprehensive evaluation of diagnostic role of circulating miRNAs in lung cancer. Eligible studies were searched in electronical databases. The sensitivity and specificity were used to plot the summary receiver operator characteristic (SROC) curve and calculate the area under the curve (AUC). The between-study heterogeneity was evaluated by Q test and I² statistics. Subgroup analyses and meta-regression were further performed to explore the potential sources of heterogeneity. A total of 134 studies from 65 articles (6,919 patients with lung cancer and 7,064 controls) were included for analysis. Overall analysis showed that circulating miRNAs had a good diagnostic performance in lung cancers, with a sensitivity of 0.83, a specificity of 0.84, and an AUC of 0.90. Subgroup analysis suggested that combined miRNAs and Caucasian populations may yield relatively higher diagnostic performance. In addition, we found serum might serve as an ideal material to detecting miRNA as good diagnostic performance. We also found the diagnostic role of miRNAs in early stage lung cancer was still relatively high (the sensitivity, specificity and an AUC of stage I/II was 0.81, 0.82 and 0.88; and for stage I, it was 0.80, 0.81, and 0.88). We also identified a panel of miRNAs such as miR-21-5p, miR-223-3p, miR-155-5p and miR-126-3p might serve as potential biomarkers for lung cancer. As a result, circulating miRNAs, particularly the combination of multiple miRNAs, may serve as promising biomarkers for the diagnosis of lung cancer.

• circulating microRNAs
• diagnostic value
• lung cancer
• meta-analysis