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Early detection of lung adenocarcinoma in sputum by a panel of microRNA markers.

ABSTRACT: Adenocarcinoma is the most common type of lung cancer, the leading cause of cancer deaths in the world. Early detection is the key to improve the survival of lung adenocarcinoma patients. We have previously shown that microRNAs (miRNAs) were stably present in sputum and could be applied to diagnosis of lung cancer. The aim of our study was to develop a panel of miRNAs that can be used as highly sensitive and specific sputum markers for early detection of lung adenocarcinoma. Our study contained 3 phases: (i) marker discovery using miRNA profiling on paired normal and tumor lung tissues from 20 patients with lung adenocarcinoma; (ii) marker optimization by real-time reverse transcription-quantitative polymerase chain reaction on sputum of a case-control cohort consisting of 36 cancer patients and 36 health individuals and (iii) validation on an independent set of 64 lung cancer patients and 58 cancer-free subjects. From the surgical tissues, 7 miRNAs with significantly altered expression were identified, of which "4" were overexpressed and "3" were underexpressed in all 20 tumors. On the sputum samples of the case-control cohort, 4 (miR-21, miR-486, miR-375 and miR-200b) of the 7 miRNAs were selected, which in combination produced the best prediction in distinguishing lung adenocarcinoma patients from normal subjects with 80.6% sensitivity and 91.7% specificity. Validation of the marker panel in the independent populations confirmed the sensitivity and specificity that provided a significant improvement over any single one alone. The sputum markers demonstrated the potential of translation to laboratory settings for improving the early detection of lung adenocarcinoma.

SUBMITTER: Yu L

PROVIDER: S-EPMC3545471 | biostudies-literature | 2010 Dec

REPOSITORIES: biostudies-literature

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Early detection of lung adenocarcinoma in sputum by a panel of microRNA markers.

Yu Lei L Todd Nevins W NW Xing Lingxiao L Xie Ying Y Zhang Howard H Liu Zhenqiu Z Fang Hongbin H Zhang Jian J Katz Ruth L RL Jiang Feng F

International journal of cancer 20101201 12

Adenocarcinoma is the most common type of lung cancer, the leading cause of cancer deaths in the world. Early detection is the key to improve the survival of lung adenocarcinoma patients. We have previously shown that microRNAs (miRNAs) were stably present in sputum and could be applied to diagnosis of lung cancer. The aim of our study was to develop a panel of miRNAs that can be used as highly sensitive and specific sputum markers for early detection of lung adenocarcinoma. Our study contained ...[more]

PMID: 21351266

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Project description:Background: We previously identified a 12-microRNA (miRNA) panel (miRNA-17, miRNA-146a, miRNA-200b, miRNA-182, miRNA-155, miRNA-221, miRNA-205, miRNA-126, miRNA-7, miRNA-21, miRNA-145, and miRNA-210) that aided in the early diagnosis of non-small cell lung cancer (NSCLC). We validated the diagnostic value of this miRNA panel and compared it with that of traditional tumor markers and radiological diagnosis. We constructed a nomogram based on the miRNA panel's results to predict the risk of NSCLC. Methods: Eighty-two participants with pulmonary nodules on a CT scan and who underwent a pathological examination and surgical treatment were enrolled in our study. Patients were randomly divided into a training group or a validation group. The miRNA concentrations were quantified by RT-PCR and log-transformed for analysis. The cutoff value was determined in the training group and then applied in the validation group. A comparison between the miRNAs and traditional tumor markers [CEA, NSE, and cytokeratin 19 fragment 21-1 (Cyfra21-1)] and radiological diagnosis was performed. A nomogram based on the miRNA panel's results to predict the risk of NSCLC was constructed. Results: The expression level of these 12 miRNAs was significantly higher in NSCLC patients than in benign patients. In the validation group, the specificity and positive predictive value were 96.4 and 95.8%, respectively, which were significantly higher than those using traditional tumor markers or radiological diagnosis. The sensitivity was 42.6%, which was also higher than that using tumor markers. Moreover, the sensitivity increased to 63.6% when the nodule diameters were larger than 2 cm. The miRNAs and seven clinical factors were integrated into the nomogram, and the calibration curves showed optimal agreement between the predicted and actual probabilities. Conclusions: Our miRNA panel has clinical value for the early detection of NSCLC. A nomogram was constructed and internally validated, and the results indicate that it can assist clinicians in making treatment recommendations in the clinic.

Dataset Information

Early detection of lung adenocarcinoma in sputum by a panel of microRNA markers.

Publications

Early detection of lung adenocarcinoma in sputum by a panel of microRNA markers.

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