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Analysis of MicroRNAs in sputum to improve computed tomography for lung cancer diagnosis.

ABSTRACT: Computed tomography (CT) plays a central role in lung cancer diagnosis. However, CT has relatively low specificity, presenting a challenge in clinical settings. We previously identified 12 microRNAs (miRNAs) whose expressions in tumor tissues were associated with lung cancer.Using quantitative reverse transcriptase polymerase chain reaction, we aimed to identify miRNA biomarkers in sputum that could complement CT for diagnosis of lung cancer.In a training set consisting of 66 lung cancer patients and 68 cancer-free smokers, 10 of the 12 miRNAs were differentially expressed between the cases and controls (p ? 0.01). From the miRNAs, a logistic regression model was built on the basis of miR-31 and miR-210, both of which had the best prediction for lung cancer, producing an area under receiver operating characteristic curve of 0.83. Combined use of the two miRNAs yielded 65.2% sensitivity and 89.7% specificity, CT had 93.9% sensitivity and 83.8% specificity for lung cancer diagnosis. Notably, combined analysis of the miRNA biomarkers and CT produced a higher specificity than does CT used alone (91.2% versus 83.8%; p < 0.05). The diagnostic performance of the biomarkers was confirmed in a testing set comprising 64 lung cancer patients and 73 cancer-free smokers.The sputum miRNA biomarkers might be useful in improving CT for diagnosis of lung cancer, but further independent validation on an external and prospective cohort of patients is required.

SUBMITTER: Shen J

PROVIDER: S-EPMC4967496 | biostudies-literature | 2014 Jan

REPOSITORIES: biostudies-literature

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Analysis of MicroRNAs in sputum to improve computed tomography for lung cancer diagnosis.

Shen Jun J Liao Jipei J Guarnera Maria A MA Fang HongBin H Cai Ling L Stass Sanford A SA Jiang Feng F

Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer 20140101 1

<h4>Introduction</h4>Computed tomography (CT) plays a central role in lung cancer diagnosis. However, CT has relatively low specificity, presenting a challenge in clinical settings. We previously identified 12 microRNAs (miRNAs) whose expressions in tumor tissues were associated with lung cancer.<h4>Methods</h4>Using quantitative reverse transcriptase polymerase chain reaction, we aimed to identify miRNA biomarkers in sputum that could complement CT for diagnosis of lung cancer.<h4>Results</h4>I ...[more]

PMID: 24305007

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Project description:ImportanceThe American College of Radiology (ACR) has recognized the importance of minimizing radiation doses used for lung cancer screening (LCS) computed tomography (CT). However, without standard protocols, doses could still be unnecessarily high, reducing screening margin of benefit.ObjectiveTo characterize LCS CT radiation doses and identify factors explaining variation.Design, setting, and participantsWe prospectively collected LCS examination dose metrics, from 2016 to 2017, at US institutions in the University of California, San Francisco International Dose Registry. Institution-level factors were collected through baseline survey. Mixed-effects linear and logistic regression models were estimated using forward variable selection. Results are presented as percentage excess dose and odds ratios (ORs) with 95% confidence intervals (CIs). The analysis was conducted between 2018 and 2019.Main outcomes and measuresLog-transformed measures of (1) mean volume CT dose index (CTDIvol, mGy), reflecting the average radiation dose per slice; (2) mean effective dose (ED, mSv), reflecting the total dose received and estimated future cancer risk; (3) proportion of CT scans using radiation doses above ACR benchmarks (CTDIvol >3 mGy, ED >1 mSv); and (4) proportion of CT scans using radiation doses above 75th percentile of registry doses (CTDIvol >2.7 mGy, ED >1.4 mSv).ResultsData were collected for 12 529 patients undergoing LCS CT scans performed at 72 institutions. Overall, 7232 participants (58%) were men, and the median age was 65 years (interquartile range [IQR], 60-70). Of 72 institutions, 15 (21%) had median CTDIvol and 47 (65%) had median ED above ACR guidelines. Institutions allowing any radiologists to establish protocols had 44% higher mean CTDIvol (mean dose difference [MDD], 44%; 95% CI, 19%-69%) and 27% higher mean ED (MDD, 27%; 95% CI, 5%-50%) vs those limiting who established protocols. Institutions allowing any radiologist to establish protocols had higher odds of examinations exceeding ACR CTDIvol guidelines (OR, 12.0; 95% CI, 2.0-71.4), and 75th percentile of registry CTDIvol (OR, 19.0; 95% CI, 1.9-186.7) or ED (OR, 8.5; 95% CI, 1.7-42.9). Having lead radiologists establish protocols resulted in lower odds of doses exceeding ACR ED guidelines (OR, 0.01; 95% CI, 0.001-0.1). Employing external vs internal medical physicists was associated with increased odds of exceeding ACR CTDIvol guidelines (OR, 6.1; 95% CI, 1.8-20.8). Having medical physicists establish protocols was associated with decreased odds of exceeding 75th percentile of registry CTDIvol (OR, 0.09; 95% CI, 0.01-0.59). Institutions reporting protocol updates as needed had 27% higher mean CTDIvol (MDD, 27%; 95% CI, 8%-45%).Conclusions and relevanceFacilities varied in LCS CT radiation dose distributions. Institutions limiting protocol creation to lead radiologists and having internal medical physicists had lower doses.

Project description:ImportanceScreening for lung cancer has the potential to reduce mortality, but in addition to detecting aggressive tumors, screening will also detect indolent tumors that otherwise may not cause clinical symptoms. These overdiagnosis cases represent an important potential harm of screening because they incur additional cost, anxiety, and morbidity associated with cancer treatment.ObjectiveTo estimate overdiagnosis in the National Lung Screening Trial (NLST).Design, setting, and participantsWe used data from the NLST, a randomized trial comparing screening using low-dose computed tomography (LDCT) vs chest radiography (CXR) among 53 452 persons at high risk for lung cancer observed for 6.4 years, to estimate the excess number of lung cancers in the LDCT arm of the NLST compared with the CXR arm.Main outcomes and measuresWe calculated 2 measures of overdiagnosis: the probability that a lung cancer detected by screening with LDCT is an overdiagnosis (PS), defined as the excess lung cancers detected by LDCT divided by all lung cancers detected by screening in the LDCT arm; and the number of cases that were considered overdiagnosis relative to the number of persons needed to screen to prevent 1 death from lung cancer.ResultsDuring follow-up, 1089 lung cancers were reported in the LDCT arm and 969 in the CXR arm of the NLST. The probability is 18.5% (95% CI, 5.4%-30.6%) that any lung cancer detected by screening with LDCT was an overdiagnosis, 22.5% (95% CI, 9.7%-34.3%) that a non-small cell lung cancer detected by LDCT was an overdiagnosis, and 78.9% (95% CI, 62.2%-93.5%) that a bronchioalveolar lung cancer detected by LDCT was an overdiagnosis. The number of cases of overdiagnosis found among the 320 participants who would need to be screened in the NLST to prevent 1 death from lung cancer was 1.38.Conclusions and relevanceMore than 18% of all lung cancers detected by LDCT in the NLST seem to be indolent, and overdiagnosis should be considered when describing the risks of LDCT screening for lung cancer.

Dataset Information

Analysis of MicroRNAs in sputum to improve computed tomography for lung cancer diagnosis.

Publications

Analysis of MicroRNAs in sputum to improve computed tomography for lung cancer diagnosis.

Similar Datasets

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