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Circulating MicroRNA Biomarkers for Lung Cancer Detection in East Asian Populations.

ABSTRACT: BACKGROUND:Lung cancer (LC) is the leading cause of cancer-related death in Eastern Asia. The prognosis of LC highly depends on tumor stages and early detection could substantially reduce LC mortality. Accumulating evidence suggested that circulating miRNAs in plasma or serum may have applications in early LC detection. We thus conducted a systematic literature review on the diagnostic value of miRNAs markers for LC in East Asian populations. METHODS:PubMed and ISI Web of Knowledge were searched to retrieve relevant articles published up to 17 September 2018. Information on study design, population characteristics, investigated miRNAs and diagnostic accuracy (including sensitivity, specificity and area under the curve (AUC)) were independently extracted by two reviewers. RESULTS:Overall, 46 studies that evaluated a total of 88 miRNA markers for LC diagnosis in East Asian populations were identified. Sixteen of the 46 studies have incorporated individual miRNA markers as panels (with 2?20 markers). Three promising miRNA panels with ?90% sensitivity and ?90% specificity were discovered, two of which were externally validated. Diagnostic performance of circulating miRNAs in East Asian populations was comparable to previously summarized performance in Western populations. Forty-four miRNAs were reported in both populations. No major differences in diagnostic performance by ethnicity of the same miRNA was observed. CONCLUSIONS:Circulating miRNAs or miRNA panels, possibly in combination with other promising molecular markers including epigenetic and genetic markers, may be promising candidates for noninvasive LC early detection. However, large studies with samples collected prospectively in true screening settings are required to validate the promising markers or marker panels.

SUBMITTER: Yu H

PROVIDER: S-EPMC6468694 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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Circulating MicroRNA Biomarkers for Lung Cancer Detection in East Asian Populations.

Yu Haixin H Guan Zhong Z Cuk Katarina K Zhang Yan Y Brenner Hermann H

Cancers 20190323 3

<h4>Background</h4>Lung cancer (LC) is the leading cause of cancer-related death in Eastern Asia. The prognosis of LC highly depends on tumor stages and early detection could substantially reduce LC mortality. Accumulating evidence suggested that circulating miRNAs in plasma or serum may have applications in early LC detection. We thus conducted a systematic literature review on the diagnostic value of miRNAs markers for LC in East Asian populations.<h4>Methods</h4>PubMed and ISI Web of Knowledg ...[more]

PMID: 30909610

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Project description:ObjectiveSince the inefficient cancer management is caused by inaccurate diagnoses, there is a need for minimally invasive method to improve the diagnostic accuracy of non-small-cell lung (NSCLC). This study intended to detect miR-340 and miR-450b-5p levels in plasma from NSCLC patients and to assess the potential values for the prediction of tumor development and prognosis.MethodsA GSE64591 dataset included 200 samples (100 early-stage NSCLC patients and 100 noncancer control) aimed to identify a panel of circulating miRNAs in plasma. The levels of miR-340 and miR-450b-5p in plasma from NSCLC patients (n = 120) and healthy controls (n = 120) were detected by quantitative real-time polymerase chain reaction (qRT-PCR). The diagnostic and prognostic value of plasma miR-340 and miR-450b-5p were performed using receiver operating curves (ROC), Kaplan-Meier method, and Cox regression analysis.ResultsmiR-450b-5p and miR-340 in plasma was significant difference between early-stage NSCLC patients and noncancer control by searching the GSE64591 dataset. When compared with the healthy controls, the plasma miR-340 was decreased in the NSCLC patients, but the plasma miR-450b-5p was increased. NSCLC patients could be distinguished accurately from healthy controls by the circulating miR-340 and miR-450b-5p with the AUC of 0.740 (95% CI: 0.677~0.804) and of 0.808 (95% CI: 0.754~0.861), respectively. With these two markers, the specificity and sensitivity were 78.33% and 77.5% with the AUC of 0.862. Patients with advanced T, N, and TNM stage demonstrated lower plasma miR-340 and higher plasma miR-450b-5p, and both of them were correlated with the prognosis of NSCLC patients. Furthermore, plasma miR-340 was also negatively correlated with tumor grade. All clinicopathological variables significantly associated to prognosis were T stage, N stage, TNM stage, tumor grade, and plasma levels of miR-340 and miR-450b-5p in univariate Cox regression analysis. The variables that retained their significance in the multivariate model were T stage, plasma miR-340, and plasma miR-450b-5p.ConclusionThe plasma levels of miR-340 combined with miR-450b-5p potentially define core biomarker signatures for improving the accuracy of NSCLC diagnosis. Moreover, circulating miR-340 and miR-450b-5p are independent biomarkers of survival in nonmetastatic NSCLC patients.

Project description:ImportanceThe overall low survival rate of patients with lung cancer calls for improved detection tools to enable better treatment options and improved patient outcomes. Multivariable molecular signatures, such as blood-borne microRNA (miRNA) signatures, may have high rates of sensitivity and specificity but require additional studies with large cohorts and standardized measurements to confirm the generalizability of miRNA signatures.ObjectiveTo investigate the use of blood-borne miRNAs as potential circulating markers for detecting lung cancer in an extended cohort of symptomatic patients and control participants.Design, setting, and participantsThis multicenter, cohort study included patients from case-control and cohort studies (TREND and COSYCONET) with 3102 patients being enrolled by convenience sampling between March 3, 2009, and March 19, 2018. For the cohort study TREND, population sampling was performed. Clinical diagnoses were obtained for 3046 patients (606 patients with non-small cell and small cell lung cancer, 593 patients with nontumor lung diseases, 883 patients with diseases not affecting the lung, and 964 unaffected control participants). No samples were removed because of experimental issues. The collected data were analyzed between April 2018 and November 2019.Main outcomes and measuresSensitivity and specificity of liquid biopsy using miRNA signatures for detection of lung cancer.ResultsA total of 3102 patients with a mean (SD) age of 61.1 (16.2) years were enrolled. Data on the sex of the participants were available for 2856 participants; 1727 (60.5%) were men. Genome-wide miRNA profiles of blood samples from 3046 individuals were evaluated by machine-learning methods. Three classification scenarios were investigated by splitting the samples equally into training and validation sets. First, a 15-miRNA signature from the training set was used to distinguish patients diagnosed with lung cancer from all other individuals in the validation set with an accuracy of 91.4% (95% CI, 91.0%-91.9%), a sensitivity of 82.8% (95% CI, 81.5%-84.1%), and a specificity of 93.5% (95% CI, 93.2%-93.8%). Second, a 14-miRNA signature from the training set was used to distinguish patients with lung cancer from patients with nontumor lung diseases in the validation set with an accuracy of 92.5% (95% CI, 92.1%-92.9%), sensitivity of 96.4% (95% CI, 95.9%-96.9%), and specificity of 88.6% (95% CI, 88.1%-89.2%). Third, a 14-miRNA signature from the training set was used to distinguish patients with early-stage lung cancer from all individuals without lung cancer in the validation set with an accuracy of 95.9% (95% CI, 95.7%-96.2%), sensitivity of 76.3% (95% CI, 74.5%-78.0%), and specificity of 97.5% (95% CI, 97.2%-97.7%).Conclusions and relevanceThe findings of the study suggest that the identified patterns of miRNAs may be used as a component of a minimally invasive lung cancer test, complementing imaging, sputum cytology, and biopsy tests.

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Circulating MicroRNA Biomarkers for Lung Cancer Detection in East Asian Populations.

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Circulating MicroRNA Biomarkers for Lung Cancer Detection in East Asian Populations.

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