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Diagnostic Value of Serum miR-182, miR-183, miR-210, and miR-126 Levels in Patients with Early-Stage Non-Small Cell Lung Cancer.

Zhu W, Zhou K, Zha Y, Chen D, He J, Ma H, Liu X, Le H, Zhang Y - PLoS ONE (2016)

Bottom Line: Blood-circulating miRNAs could be useful as a biomarker to detect lung cancer early.The data showed that the serum levels of miR-182, miR-183, and miR-210 were significantly upregulated and that the miR-126 level was significantly downregulated in NSCLC patients, compared with the healthy controls.Data from the current study validated that the four serum miRNAs could serve as a tumor biomarker for NSCLC early diagnosis.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Cytobiology and Molecular Biology, Zhoushan Hospital of Wenzhou Medical University, Zhoushan, Zhejiang, 316021, China.

ABSTRACT
Blood-circulating miRNAs could be useful as a biomarker to detect lung cancer early. We investigated the serum levels of four different miRNAs in patients with non-small cell lung cancer (NSCLC) and assessed their diagnostic value for NSCLC. Serum samples from 112 NSCLC patients and 104 controls (20 current smokers without lung cancer, 23 pneumonia patients, 21 gastric cancer patients, and 40 healthy controls) were subjected to Taqman probe-based quantitative reverse transcription-polymerase chain reaction (RT-PCR). The data showed that the serum levels of miR-182, miR-183, and miR-210 were significantly upregulated and that the miR-126 level was significantly downregulated in NSCLC patients, compared with the healthy controls. Further receiver operating characteristic (ROC) curve analysis revealed that the serum miR-182, miR-183, miR-210, or miR-126 level could serve as a diagnostic biomarker for NSCLC early detection, with a high sensitivity and specificity. The combination of these four miRNAs with carcinoembryonic antigen (CEA) further increased the diagnostic value, with an area under the curve (AUC) of 0.965 (sensitivity, 81.3%; specificity, 100.0%; and accuracy, 90.8%) using logistic regression model analysis. In addition, the relative levels of serum miR-182, miR-183, miR-210, and miR-126 could distinguish NSCLC or early-stage NSCLC from current tobacco smokers without lung cancer and pneumonia or gastric cancer patients with a high sensitivity and specificity. Data from the current study validated that the four serum miRNAs could serve as a tumor biomarker for NSCLC early diagnosis.

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ROC curves to assess the value of serum miRNA and CEA levels in NSCLC patients compared to 40 healthy controls.The P values of serum miR-182, miR-183, miR-210, miR-126, and CEA as well as the predictive value of logistic regression were < 0.0001, 0.0091, 0.0121, < 0.0001, < 0.0001, and < 0.0001, respectively.
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pone.0153046.g003: ROC curves to assess the value of serum miRNA and CEA levels in NSCLC patients compared to 40 healthy controls.The P values of serum miR-182, miR-183, miR-210, miR-126, and CEA as well as the predictive value of logistic regression were < 0.0001, 0.0091, 0.0121, < 0.0001, < 0.0001, and < 0.0001, respectively.

Mentions: Next, we performed ROC curve analysis to evaluate the diagnostic value of these four serum- circulating miRNAs and CEA. First, we identified a cut-off value that distinguished 112 NSCLC patients from 40 healthy sex- and age-matched controls. The ROC curve data showed that all four of these miRNAs could distinguish the NSCLC patients from the controls. Specifically, the serum level of miR-182 had a sensitivity of 63.4% and a specificity of 80.0% to differentiate the NSCLC patients from the healthy controls, with an AUC of 0.734 at the optimal cut-off point (P < 0.0001, 95% confidence interval [CI]: 0.657–0.803). miR-183 had a sensitivity of 41.1% and a specificity of 82.5%, with an AUC of 0.626 (P = 0.0091, 95% CI: 0.544–0.703). miR-210 had a sensitivity of 33.9% and a specificity of 100.0%, with an AUC of 0.616 (P = 0.0121, 95% CI: 0.534–0.694). miR-126 had a sensitivity of 60.7% and a specificity of 92.5%, with an AUC of 0.793 (P < 0.0001, 95% CI: 0.719–0.854). CEA had a sensitivity of 55.4% and a specificity of 77.5%, with an AUC of 0.711 (P < 0.0001, 95% CI: 0.632–0.782; Fig 3). Clinically, the serum CEA level is routinely used for cancer detection. Thus, we compared the AUC of CEA with that of the four miRNAs and found that the diagnostic value of CEA was not significantly different from those of miR-182, miR-183, miR-210, and miR-126 (P = 0.7290, 0.2056, 0.1818, and 0.1271, respectively). However, the predicted values of logistic regression analysis showed that the combined ROC analysis of these four miRNAs plus CEA revealed an increased AUC value of 0.965, with a sensitivity of 81.3%, a specificity of 100.0%, and an accuracy of 90.8% (P < 0.0001, 95% CI: 0.923–0.988; Fig 3 and Table 2). The multivariate logistic regression analysis of the ROC curve of these four miRNAs plus CEA is shown in S1 Table.


Diagnostic Value of Serum miR-182, miR-183, miR-210, and miR-126 Levels in Patients with Early-Stage Non-Small Cell Lung Cancer.

Zhu W, Zhou K, Zha Y, Chen D, He J, Ma H, Liu X, Le H, Zhang Y - PLoS ONE (2016)

ROC curves to assess the value of serum miRNA and CEA levels in NSCLC patients compared to 40 healthy controls.The P values of serum miR-182, miR-183, miR-210, miR-126, and CEA as well as the predictive value of logistic regression were < 0.0001, 0.0091, 0.0121, < 0.0001, < 0.0001, and < 0.0001, respectively.
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4836744&req=5

pone.0153046.g003: ROC curves to assess the value of serum miRNA and CEA levels in NSCLC patients compared to 40 healthy controls.The P values of serum miR-182, miR-183, miR-210, miR-126, and CEA as well as the predictive value of logistic regression were < 0.0001, 0.0091, 0.0121, < 0.0001, < 0.0001, and < 0.0001, respectively.
Mentions: Next, we performed ROC curve analysis to evaluate the diagnostic value of these four serum- circulating miRNAs and CEA. First, we identified a cut-off value that distinguished 112 NSCLC patients from 40 healthy sex- and age-matched controls. The ROC curve data showed that all four of these miRNAs could distinguish the NSCLC patients from the controls. Specifically, the serum level of miR-182 had a sensitivity of 63.4% and a specificity of 80.0% to differentiate the NSCLC patients from the healthy controls, with an AUC of 0.734 at the optimal cut-off point (P < 0.0001, 95% confidence interval [CI]: 0.657–0.803). miR-183 had a sensitivity of 41.1% and a specificity of 82.5%, with an AUC of 0.626 (P = 0.0091, 95% CI: 0.544–0.703). miR-210 had a sensitivity of 33.9% and a specificity of 100.0%, with an AUC of 0.616 (P = 0.0121, 95% CI: 0.534–0.694). miR-126 had a sensitivity of 60.7% and a specificity of 92.5%, with an AUC of 0.793 (P < 0.0001, 95% CI: 0.719–0.854). CEA had a sensitivity of 55.4% and a specificity of 77.5%, with an AUC of 0.711 (P < 0.0001, 95% CI: 0.632–0.782; Fig 3). Clinically, the serum CEA level is routinely used for cancer detection. Thus, we compared the AUC of CEA with that of the four miRNAs and found that the diagnostic value of CEA was not significantly different from those of miR-182, miR-183, miR-210, and miR-126 (P = 0.7290, 0.2056, 0.1818, and 0.1271, respectively). However, the predicted values of logistic regression analysis showed that the combined ROC analysis of these four miRNAs plus CEA revealed an increased AUC value of 0.965, with a sensitivity of 81.3%, a specificity of 100.0%, and an accuracy of 90.8% (P < 0.0001, 95% CI: 0.923–0.988; Fig 3 and Table 2). The multivariate logistic regression analysis of the ROC curve of these four miRNAs plus CEA is shown in S1 Table.

Bottom Line: Blood-circulating miRNAs could be useful as a biomarker to detect lung cancer early.The data showed that the serum levels of miR-182, miR-183, and miR-210 were significantly upregulated and that the miR-126 level was significantly downregulated in NSCLC patients, compared with the healthy controls.Data from the current study validated that the four serum miRNAs could serve as a tumor biomarker for NSCLC early diagnosis.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Cytobiology and Molecular Biology, Zhoushan Hospital of Wenzhou Medical University, Zhoushan, Zhejiang, 316021, China.

ABSTRACT
Blood-circulating miRNAs could be useful as a biomarker to detect lung cancer early. We investigated the serum levels of four different miRNAs in patients with non-small cell lung cancer (NSCLC) and assessed their diagnostic value for NSCLC. Serum samples from 112 NSCLC patients and 104 controls (20 current smokers without lung cancer, 23 pneumonia patients, 21 gastric cancer patients, and 40 healthy controls) were subjected to Taqman probe-based quantitative reverse transcription-polymerase chain reaction (RT-PCR). The data showed that the serum levels of miR-182, miR-183, and miR-210 were significantly upregulated and that the miR-126 level was significantly downregulated in NSCLC patients, compared with the healthy controls. Further receiver operating characteristic (ROC) curve analysis revealed that the serum miR-182, miR-183, miR-210, or miR-126 level could serve as a diagnostic biomarker for NSCLC early detection, with a high sensitivity and specificity. The combination of these four miRNAs with carcinoembryonic antigen (CEA) further increased the diagnostic value, with an area under the curve (AUC) of 0.965 (sensitivity, 81.3%; specificity, 100.0%; and accuracy, 90.8%) using logistic regression model analysis. In addition, the relative levels of serum miR-182, miR-183, miR-210, and miR-126 could distinguish NSCLC or early-stage NSCLC from current tobacco smokers without lung cancer and pneumonia or gastric cancer patients with a high sensitivity and specificity. Data from the current study validated that the four serum miRNAs could serve as a tumor biomarker for NSCLC early diagnosis.

Show MeSH
Related in: MedlinePlus