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Clinical biomarkers of pulmonary carcinoid tumors in never smokers via profiling miRNA and target mRNA.

ABSTRACT: BACKGROUND:miRNAs play key regulatory roles in cellular pathological processes. We aimed to identify clinically meaningful biomarkers in pulmonary carcinoid tumors (PCTs), a member of neuroendocrine neoplasms, via profiling miRNAs and mRNAs. RESULTS:From the total of 1145 miRNAs, we obtained 16 and 17 miRNAs that showed positive and negative fold changes (FCs, tumors vs. normal tissues) in the top 1% differentially expressed miRNAs, respectively. We uncovered the target genes that were predicted by at least two prediction tools and overlapped by at least one-half of the top miRNAs, which yielded 44 genes (FC<-2) and 56 genes (FC>2), respectively. Higher expressions of CREB5, PTPRB and COL4A3 predicted favorable disease free survival (Hazard ratio: 0.03, 0.19 and 0.36; P value: 0.03, 0.03 and 0.08). Additionally, 79 mutated genes have been found in nine PCTs where TP53 was the only repeated mutation. CONCLUSION:We identified that the expressions of three genes have clinical implications in PCTs. The biological functions of these biomarkers warrant further studies.

SUBMITTER: Deng B

PROVIDER: S-EPMC4124500 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Clinical biomarkers of pulmonary carcinoid tumors in never smokers via profiling miRNA and target mRNA.

Deng Bo B Molina Julian J Aubry Marie C MC Sun Zhifu Z Wang Liang L Eckloff Bruce W BW Vasmatzis George G You Ming M Wieben Eric D ED Jen Jin J Wigle Dennis A DA Yang Ping P

Cell & bioscience 20140709

<h4>Background</h4>miRNAs play key regulatory roles in cellular pathological processes. We aimed to identify clinically meaningful biomarkers in pulmonary carcinoid tumors (PCTs), a member of neuroendocrine neoplasms, via profiling miRNAs and mRNAs.<h4>Results</h4>From the total of 1145 miRNAs, we obtained 16 and 17 miRNAs that showed positive and negative fold changes (FCs, tumors vs. normal tissues) in the top 1% differentially expressed miRNAs, respectively. We uncovered the target genes that ...[more]

PMID: 25105010

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Project description:BackgroundChronic obstructive pulmonary disease (COPD) is significantly underdiagnosed in Kazakhstan, and there is no previously conducted study on COPD prevalence in the country.ObjectiveThe purpose of this study is to assess the prevalence of COPD among individuals aged 40 to 59 years based on results of spirometry before and after bronchodilator, presence of structural changes in the lungs (emphysema, inflammatory changes, and thickening of the walls of the large and small airways) detected by computer tomography, and the symptoms of COPD. The study has 3 study groups: smokers of conventional cigarettes, those who had quit smoking 1 to 5 years ago, and those who haven't smoked cigarettes.MethodsThis is an observational study with a cross-sectional design among individuals aged 40 to 59 years in Almaty, Kazakhstan. The sample of 900 individuals of both sexes contains 500 smokers, 200 ex-smokers, and 200 never-smokers. Study measures include spirometry, chest computed tomography, electrocardiography, physical exams, laboratory testing of serum, anthropometry, and 6-minute walk test. Data are collected by computer-assisted personal interviewing with tablets. The questionnaire was designed to explore possible COPD risk factors including history of smoking, current smoking, level of smoking exposure (in pack-years), passive smoking, occupational and environmental hazards, and covariates: age, gender, ethnicity, education, occupation, and self-reported morbidity. COPD Assessment Test (CAT) is used to collect information about COPD symptoms.ResultsWe have completed the participant recruitment and study procedures. Currently, we are working on data processing and data analysis. The authors anticipate the preliminary results should be available by September 2017. Study results will be published in peer-reviewed scientific journals.ConclusionsThis is the first study in Kazakhstan that assesses prevalence of COPD and its comorbidities in the adult population aged 40 to 59 years. The results of the study will be useful for improving COPD preventive measures, better COPD screening, identification, and registration. Findings of the study will also contribute to global knowledge on the epidemiology of COPD.Trial registrationClinicalTrials.gov NCT02926534; https://clinicaltrials.gov/ct2/show/NCT02926534 (Archived by WebCite at http://www.webcitation.org/6rjwGsPOZ).

Project description:Background and objectiveLung cancer is the leading cause of cancer-related mortality worldwide, partially attributed to late-stage diagnoses. In order to mitigate this, lung cancer screening (LCS) of high-risk patients is performed using low dose computed tomography (CT) scans, however this method is burdened by high false-positive rates and radiation exposure for patients. Further, screening programs focus on individuals with heavy smoking histories, and as such, never-smokers who may otherwise be at risk of lung cancer are often overlooked. To resolve these limitations, biomarkers have been posited as potential supplements or replacements to low-dose CT, and as such, a large body of research in this area has been produced. However, comparatively little information exists on their clinical efficacy and how this compares to current LCS strategies.MethodsHere we conduct a search and narrative review of current literature surrounding biomarkers of lung cancer to supplement LCS, and biomarkers of lung cancer in never-smokers (LCINS).Key content and findingsMany potential biomarkers of lung cancer have been identified with varying levels of sensitivity, specificity, clinical efficacy, and supporting evidence. Of the markers identified, multi-target panels of circulating microRNAs, lipids, and metabolites are likely the most clinically efficacious markers to aid current screening programs, as these provide the highest sensitivity and specificity for lung cancer detection. However, circulating lipid and metabolite levels are known to vary in numerous systemic pathologies, highlighting the need for further validation in large cohort randomised studies.ConclusionsLung cancer biomarkers is a fast-expanding area of research and numerous biomarkers with potential clinical applications have been identified. However, in all cases the level of evidence supporting clinical efficacy is not yet at a level at which it can be translated to clinical practice. The priority now should be to validate existing candidate markers in appropriate clinical contexts and work to integrating these into clinical practice.

Dataset Information

Clinical biomarkers of pulmonary carcinoid tumors in never smokers via profiling miRNA and target mRNA.

Publications

Clinical biomarkers of pulmonary carcinoid tumors in never smokers via profiling miRNA and target mRNA.

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