Analysis of MicroRNAs in Sputum to Improve Computed Tomography for Lung Cancer Diagnosis

Abstract

Introduction 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. Methods Using quantitative reverse transcriptase polymerase chain reaction, we aimed to identify miRNA biomarkers in sputum that could complement CT for diagnosis of lung cancer. Results 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. Conclusion 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.

Identification of miRNA biomarkers of pneumonia using RNA-sequencing and bioinformatics analysis

“…miR-200b has an important role in lung cancer development; reportedly, aberrant expression of miR-200b in sputum may be used as a diagnostic marker for lung adenocarcinoma and squamouscell carcinoma (42). In a murine influenza pneumonia model, miR-200b-5p was predicted to be an important miRNA, connecting regulation of gene functions in repair (43).…”

Small non-coding RNA biomarkers in sputum for lung cancer diagnosis

“…We determined expressions of the five ncRNAs (miRs-21, 31, and 210, and snoRDs-66 and 78) by quantitative reverse transcriptase PCR (qRT-PCR) in the sputum samples [18, 23–27]. The panel of three miRNAs (miRs-21, 31, and 210) and panel of two snoRNAs (snoRDs-66 and 78) had a receiver operating characteristic (ROC) curve (AUC) value of 0.90 and 0.86, respectively (Fig.…”

“…There is significant interest in the development of the tumor-related ncRNAs as biomarkers for cancer diagnosis [17]. We have identified a panel of three sputum miRNA biomarkers (miRs-21, 31, and 210) with 82.9 % sensitivity and 87.8 % specificity and a panel of two snoRNA sputum biomarkers (snoRDs-66 and 78) with 74.6 % sensitivity and 83.6 % specificity for lung cancer early detection [18–20]. Since lung cancer is a heterogeneous disease featuring field defects in the airway of smokers [21, 22], a single biomarker type can’t achieve the sensitivity and specificity required for clinically diagnosing NSCLC.…”

Recent advances of microRNA-based molecular diagnostics to reduce false-positive lung cancer imaging

“…The two miRNAs were able to improve specificity of CT from 83.8 to 91.1% [83]. In a very recent article, they include mir-21 in the signature and validate them in two cohorts composed by a total of 143 malignant and 148 benign solitary pulmonary nodules, resulting in 84% positive Figure 3.…”