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Expression of miR-29c, miR-93, and miR-429 as potential biomarkers for detection of early stage non-small lung cancer.

Zhu W, He J, Chen D, Zhang B, Xu L, Ma H, Liu X, Zhang Y, Le H - PLoS ONE (2014)

Bottom Line: Altered expression of miRNA expression contributes to human carcinogenesis.Receiver operating characteristic (ROC) curve analysis showed that at the optimal cut-off point, the areas under the ROC curve for serum levels of miR-29c and miR-429 were 0.723 and 0.727, respectively, levels which are higher than that of carcinoma embryonic antigen (0.534) in diagnosis of stage I NSCLC.The results of the current study suggest that detection of serum miR-29c and miR-429 expression should be further evaluated as a novel, non-invasive biomarker for early stage NSCLC.

View Article: PubMed Central - PubMed

Affiliation: Department of Joint Immunogenomics Laboratory, Zhoushan Hospital, Zhoushan, Zhejiang, China.

ABSTRACT

Background: Altered expression of miRNA expression contributes to human carcinogenesis. This study was designed to detect aberrant miRNA expressions as a potential biomarker for early detection and prognosis prediction of non-small cell lung cancer (NSCLC).

Methods: miRNA array was used to profile differentially expressed miRNAs and Taqman-based quantitative RT-PCR assays were used to analyze levels of miR-29c, miR-93, and miR-429 expression in NSCLC tissue samples, corresponding normal tissue samples, and serum samples from 70 NSCLC patients as well as in serum samples from 48 healthy controls.

Results: Levels of miR-29c and miR-93 expression were upregulated in NSCLC tissues, while serum levels of miR-29c were also upregulated, but levels of serum miR-429 were decreased in NSCLC. Moreover, the levels of miR-429 expression in NSCLC tissues were associated with those in serum samples. Receiver operating characteristic (ROC) curve analysis showed that at the optimal cut-off point, the areas under the ROC curve for serum levels of miR-29c and miR-429 were 0.723 and 0.727, respectively, levels which are higher than that of carcinoma embryonic antigen (0.534) in diagnosis of stage I NSCLC. In addition, serum levels of miR-429 were associated with poor overall survival of NSCLC patients. Both univariate and multivariate analyses showed that serum miR-429 level was an independent prognostic predictor for NSCLC.

Conclusions: The results of the current study suggest that detection of serum miR-29c and miR-429 expression should be further evaluated as a novel, non-invasive biomarker for early stage NSCLC.

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ROC curves for serum miRNA and CEA levels in NSCLC patients.A, miR-29c; B, miR-429; C, CEA showed ROC curves and an AUC with diagnostic power to distinguish NSCLC patients from healthy controls. D, miR-29c; E, miR-429; F, CEA showed ROC curves and an AUC with diagnostic power to distinguish stage I NSCLC patients from healthy controls.
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pone-0087780-g002: ROC curves for serum miRNA and CEA levels in NSCLC patients.A, miR-29c; B, miR-429; C, CEA showed ROC curves and an AUC with diagnostic power to distinguish NSCLC patients from healthy controls. D, miR-29c; E, miR-429; F, CEA showed ROC curves and an AUC with diagnostic power to distinguish stage I NSCLC patients from healthy controls.

Mentions: We next investigated associations between the altered miRNA expression levels (miR-29c and miR-93 in NSCLC and miR-29c and miR-429 in serum) with the clinicopathological characteristics of the NSCLC patients. We found that increased miR-93 expression was strongly associated with NSCLC histology (P = 0.031, Table 2), whereas serum miR-29c expression was associated with abnormal CEA levels (P = 0.030, Table 2). In contrast, no other associations were detected between the expression levels of these miRNAs. Furthermore, we plotted expression data for miR-29c and miR-429 using ROC curves to identify a cut-off value that could distinguish lung cancer patients from healthy controls. ROC curve analysis showed that at the optimal cut-off, serum levels of miR-29c had a sensitivity of 65.7% and a specificity of 74.1% for distinguishing NSCLC patients from healthy controls with an area under the curve (AUC) of 0.676 (P = 0.0004, 95% confidence interval [CI]: 0.584–0.759, Figure 2A). In addition, serum levels of miR-429 had a sensitivity of 54.3% and a specificity of 81.2% for distinguishing NSCLC patients from healthy controls with an AUC of 0.713 (P<0.0001, 95% CI: 0.623–0.793, Figure 2B). Because the blood CEA test is a widely used marker for NSCLC, we compared CEA results with the miRNA expression levels and found that CEA had an AUC of 0.576 (P = 0.1493, 95% CI: 0.482–0.666, Figure 2C). However, for the combination of miR-29c expression and CEA, the data showed an AUC of 0.712 (P<0.0001, 95% CI: 0.622–0.792); for the combination of miR-429 expression and CEA, the AUC was 0.707 (P = 0.0007, 95% CI: 0.616–0.787); and for the combination of miR-29c expression and miR-429 with CEA, the AUC was 0.797 (P<0.0001, 95% CI: 0.713–0.865).


Expression of miR-29c, miR-93, and miR-429 as potential biomarkers for detection of early stage non-small lung cancer.

Zhu W, He J, Chen D, Zhang B, Xu L, Ma H, Liu X, Zhang Y, Le H - PLoS ONE (2014)

ROC curves for serum miRNA and CEA levels in NSCLC patients.A, miR-29c; B, miR-429; C, CEA showed ROC curves and an AUC with diagnostic power to distinguish NSCLC patients from healthy controls. D, miR-29c; E, miR-429; F, CEA showed ROC curves and an AUC with diagnostic power to distinguish stage I NSCLC patients from healthy controls.
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
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pone-0087780-g002: ROC curves for serum miRNA and CEA levels in NSCLC patients.A, miR-29c; B, miR-429; C, CEA showed ROC curves and an AUC with diagnostic power to distinguish NSCLC patients from healthy controls. D, miR-29c; E, miR-429; F, CEA showed ROC curves and an AUC with diagnostic power to distinguish stage I NSCLC patients from healthy controls.
Mentions: We next investigated associations between the altered miRNA expression levels (miR-29c and miR-93 in NSCLC and miR-29c and miR-429 in serum) with the clinicopathological characteristics of the NSCLC patients. We found that increased miR-93 expression was strongly associated with NSCLC histology (P = 0.031, Table 2), whereas serum miR-29c expression was associated with abnormal CEA levels (P = 0.030, Table 2). In contrast, no other associations were detected between the expression levels of these miRNAs. Furthermore, we plotted expression data for miR-29c and miR-429 using ROC curves to identify a cut-off value that could distinguish lung cancer patients from healthy controls. ROC curve analysis showed that at the optimal cut-off, serum levels of miR-29c had a sensitivity of 65.7% and a specificity of 74.1% for distinguishing NSCLC patients from healthy controls with an area under the curve (AUC) of 0.676 (P = 0.0004, 95% confidence interval [CI]: 0.584–0.759, Figure 2A). In addition, serum levels of miR-429 had a sensitivity of 54.3% and a specificity of 81.2% for distinguishing NSCLC patients from healthy controls with an AUC of 0.713 (P<0.0001, 95% CI: 0.623–0.793, Figure 2B). Because the blood CEA test is a widely used marker for NSCLC, we compared CEA results with the miRNA expression levels and found that CEA had an AUC of 0.576 (P = 0.1493, 95% CI: 0.482–0.666, Figure 2C). However, for the combination of miR-29c expression and CEA, the data showed an AUC of 0.712 (P<0.0001, 95% CI: 0.622–0.792); for the combination of miR-429 expression and CEA, the AUC was 0.707 (P = 0.0007, 95% CI: 0.616–0.787); and for the combination of miR-29c expression and miR-429 with CEA, the AUC was 0.797 (P<0.0001, 95% CI: 0.713–0.865).

Bottom Line: Altered expression of miRNA expression contributes to human carcinogenesis.Receiver operating characteristic (ROC) curve analysis showed that at the optimal cut-off point, the areas under the ROC curve for serum levels of miR-29c and miR-429 were 0.723 and 0.727, respectively, levels which are higher than that of carcinoma embryonic antigen (0.534) in diagnosis of stage I NSCLC.The results of the current study suggest that detection of serum miR-29c and miR-429 expression should be further evaluated as a novel, non-invasive biomarker for early stage NSCLC.

View Article: PubMed Central - PubMed

Affiliation: Department of Joint Immunogenomics Laboratory, Zhoushan Hospital, Zhoushan, Zhejiang, China.

ABSTRACT

Background: Altered expression of miRNA expression contributes to human carcinogenesis. This study was designed to detect aberrant miRNA expressions as a potential biomarker for early detection and prognosis prediction of non-small cell lung cancer (NSCLC).

Methods: miRNA array was used to profile differentially expressed miRNAs and Taqman-based quantitative RT-PCR assays were used to analyze levels of miR-29c, miR-93, and miR-429 expression in NSCLC tissue samples, corresponding normal tissue samples, and serum samples from 70 NSCLC patients as well as in serum samples from 48 healthy controls.

Results: Levels of miR-29c and miR-93 expression were upregulated in NSCLC tissues, while serum levels of miR-29c were also upregulated, but levels of serum miR-429 were decreased in NSCLC. Moreover, the levels of miR-429 expression in NSCLC tissues were associated with those in serum samples. Receiver operating characteristic (ROC) curve analysis showed that at the optimal cut-off point, the areas under the ROC curve for serum levels of miR-29c and miR-429 were 0.723 and 0.727, respectively, levels which are higher than that of carcinoma embryonic antigen (0.534) in diagnosis of stage I NSCLC. In addition, serum levels of miR-429 were associated with poor overall survival of NSCLC patients. Both univariate and multivariate analyses showed that serum miR-429 level was an independent prognostic predictor for NSCLC.

Conclusions: The results of the current study suggest that detection of serum miR-29c and miR-429 expression should be further evaluated as a novel, non-invasive biomarker for early stage NSCLC.

Show MeSH
Related in: MedlinePlus