Dataset Information

Serum microRNA Signature Is Capable of Early Diagnosis for Non-Small Cell Lung Cancer.

ABSTRACT: Despite decades of efforts, non-small-cell lung cancer (NSCLC) remains the leading cause of cancer mortality globally primarily due to the challenge in early detection of the cancer. Being an important player in cancer development, the dysregulated miRNAs have been shown promising values as non-invasive diagnostic and prognostic biomarkers for NSCLC. The aim of our study is to access the efficacy and reliability of a potential circulating miRNA panel in early diagnosis of NSCLC. We first selected eight candidate miRNAs, miR-146b, miR-205, miR-29c, miR-31, miR-30b, miR-337, miR-411, and miR-708, which have been shown frequently aberrant in primary NSCLC patients based on our previous studies and other reports. The serum level of each of these miRNAs was evaluated by quantitative real-time PCR (qRT-PCR) in training and testing sets. We found that 5 out of 8 miRNAs (miR-146b, miR-205, miR-29c, miR-30b, and miR-337) were significantly up-regulated in NSCLCs patients compared to healthy or cancer-free controls in both training and testing sets. Based on the logistic regression model, a 4-miRNAs set (miR-146b, miR-205, miR-29c and miR-30b) was picked out of the 5 miRNAs owing to its excellent diagnostic power for NSCLC patients in the training set (AUC=0.99, accuracy=95.00%), the testing set (AUC=0.93, accuracy=89.69%), and the training-testing combined set ( AUC=0.96, accuracy=92.00%). When pathological subtypes of NSCLC are compared, this 4-miRNA panel carried a relatively higher prediction power and higher sensitivity for adenocarcinoma (AC) (AUC=0.98, sensitivity=99.10%) than for squamous cell carcinoma (SCC) (AUC=0.93, sensitivity=90.32%). Additionally, this panel demonstrated a comparable diagnostic capacity for stage I (AUC=0.96) and stage II-III (AUC=0.95) of NSCLC, suggesting its role in reflecting the tumor load. Importantly, the high levels of miR-146b and miR-29c in serum were significantly associated with poor 5-year overall survival (OS) (both p=0.04). Further survival analysis showed that high level of miR-146b in serum is specifically correlated with poor survival rate in SCC patients (p=0.0035) but not in AC patients (p=0.83), consistent with our previous finding that the high tissue expression of miR-146b in lung cancer specimen is indicative of a poor prognosis for SCC patients. Altogether, our study demonstrated that the 4-miRNA panel is a novel, sensitive and non-invasive serum marker for the early diagnosis of NSCLC.

SUBMITTER: Yang X

PROVIDER: S-EPMC6643220 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Serum microRNA Signature Is Capable of Early Diagnosis for Non-Small Cell Lung Cancer.

Yang Xia X Zhang Qiuhong Q Zhang Ming M Su Wenmei W Wang Zhuwen Z Li Yali Y Zhang Jie J Beer David G DG Yang Shuanying S Chen Guoan G

International journal of biological sciences 20190610 8

Despite decades of efforts, non-small-cell lung cancer (NSCLC) remains the leading cause of cancer mortality globally primarily due to the challenge in early detection of the cancer. Being an important player in cancer development, the dysregulated miRNAs have been shown promising values as non-invasive diagnostic and prognostic biomarkers for NSCLC. The aim of our study is to access the efficacy and reliability of a potential circulating miRNA panel in early diagnosis of NSCLC. We first selecte ...[more]

PMID: 31360113

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Project description:PURPOSE:To assess the utility of circulating serum microRNAs (c-miRNAs) to predict response to high-dose radiation therapy for locally advanced non-small cell lung cancer (NSCLC). METHODS AND MATERIALS:Data from 80 patients treated from 2004 to 2013 with definitive standard- or high-dose radiation therapy for stages II-III NSCLC as part of 4 prospective institutional clinical trials were evaluated. Pretreatment serum levels of 62 miRNAs were measured by quantitative reverse transcription-polymerase chain reaction array. We combined miRNA data and clinical factors to generate a dose-response score (DRS) for predicting overall survival (OS) after high-dose versus standard-dose radiation therapy. Elastic net Cox regression was used for variable selection and parameter estimation. Model assessment and tuning parameter selection were performed through full cross-validation. The DRS was also correlated with local progression, distant metastasis, and grade 3 or higher cardiac toxicity using Cox regression, and grade 2 or higher esophageal and pulmonary toxicity using logistic regression. RESULTS:Eleven predictive miRNAs were combined with clinical factors to generate a DRS for each patient. In patients with low DRS, high-dose radiation therapy was associated with significantly improved OS compared to treatment with standard-dose radiation therapy (hazard ratio 0.22). In these patients, high-dose radiation also conferred lower risk of distant metastasis and local progression, although the latter association was not statistically significant. Patients with high DRS exhibited similar rates of OS regardless of dose (hazard ratio 0.78). The DRS did not correlate with treatment-related toxicity. CONCLUSIONS:Using c-miRNA signature and clinical factors, we developed a DRS that identified a subset of patients with locally advanced NSCLC who derive an OS benefit from high-dose radiation therapy. This DRS may guide dose escalation in a patient-specific manner.

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.

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Serum microRNA Signature Is Capable of Early Diagnosis for Non-Small Cell Lung Cancer.

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Serum microRNA Signature Is Capable of Early Diagnosis for Non-Small Cell Lung Cancer.

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