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Low levels of cell-free circulating miR-361-3p and miR-625* as blood-based markers for discriminating malignant from benign lung tumors.

Roth C, Stückrath I, Pantel K, Izbicki JR, Tachezy M, Schwarzenbach H - PLoS ONE (2012)

Bottom Line: Microarray profiling showed that miR-361-3p and miR-625* were significantly down-regulated in serum of lung cancer patients.Moreover, the levels of miR-625* were significantly lower in patients with large cell lung cancer (LCLC, p = 0.014) and smoking patients (p = 0.030) than in patients with adenocarcinoma and non-smoking patients, respectively.A rise in the levels of both miRs was observed in the postoperative samples compared with the preoperative levels (p = 0.0001).

View Article: PubMed Central - PubMed

Affiliation: Department of Tumor Biology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

ABSTRACT
The high mortality rate of lung cancer patients is mainly due to the late stage at which lung cancer is diagnosed. For effective cancer prevention programs and early diagnosis, better blood-based markers are needed. Hence, blood-based microarray profiling of microRNA (miR) expression was performed in preoperative serum of 21 non-small cell lung cancer (NSCLC) patients and 11 healthy individuals by microfluid biochips containing 1158 different miRs. Two out of the 30 most dysregulated miRs were further validated in serum of 97 NSCLC patients, 20 patients with benign lung diseases and 30 healthy individuals by TaqMan MicroRNA Assays. Microarray profiling showed that miR-361-3p and miR-625* were significantly down-regulated in serum of lung cancer patients. Their further evaluation by quantitative RT-PCR showed that the levels of miR-361-3p and miR-625* were lower in NSCLC than in benign disease (p = 0.0001) and healthy individuals (p = 0.0001, p = 0.0005, respectively). Moreover, the levels of miR-625* were significantly lower in patients with large cell lung cancer (LCLC, p = 0.014) and smoking patients (p = 0.030) than in patients with adenocarcinoma and non-smoking patients, respectively. A rise in the levels of both miRs was observed in the postoperative samples compared with the preoperative levels (p = 0.0001). Functional analyses showed that Smad2 and TGFß1 are not dysregulated by miR-361-3p and miR-625* in the lung cell line A549, respectively. Our present pilot study suggests that miR-361-3p and miR-625* might have a protective influence on the development of NSCLC, and the quantitative assessment of these miRs in blood serum might have diagnostic potential to detect NSCLC, in particular in smokers.

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Related in: MedlinePlus

Evaluation of the diagnostic relevance of levels of total RNA and miRs in serum of healthy individuals, patients with benign lung disease and NSCLC patients.The box plots show the different, relative amounts of total RNA (A), miR-361-3p (B) and miR-625* (C) which circulate in blood of healthy individuals (n = 30), patients with benign lung disease (n = 20) and NSCLC patients (n = 97). The relative transcript levels of miRs were determined by the low cycle threshold (Ct) values. As determined by Mann and Whitney-U test, the significant p values of the statistical evaluations of serum RNA and miR levels are indicated. The ROC analysis shows the profile of sensitivity and specificity of miR-361-3p and miR-625* concentrations to discriminate NSCLC patients from patients with benign disease and healthy individuals (D). The AUC values and confidence intervals are indicated.
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pone-0038248-g002: Evaluation of the diagnostic relevance of levels of total RNA and miRs in serum of healthy individuals, patients with benign lung disease and NSCLC patients.The box plots show the different, relative amounts of total RNA (A), miR-361-3p (B) and miR-625* (C) which circulate in blood of healthy individuals (n = 30), patients with benign lung disease (n = 20) and NSCLC patients (n = 97). The relative transcript levels of miRs were determined by the low cycle threshold (Ct) values. As determined by Mann and Whitney-U test, the significant p values of the statistical evaluations of serum RNA and miR levels are indicated. The ROC analysis shows the profile of sensitivity and specificity of miR-361-3p and miR-625* concentrations to discriminate NSCLC patients from patients with benign disease and healthy individuals (D). The AUC values and confidence intervals are indicated.

Mentions: The concentrations of miR-361-3p and miR-625* were further evaluated in blood serum of 97 NSCLC patients, 20 patients with benign lung disease and 30 healthy individuals. The box plots in Fig. 2 compare the relative levels of total RNA and miRs in healthy individuals and patients with benign or malignant lung disease. Patients with benign (p = 0.0001) and malignant disease (p = 0.0001) displayed significant higher concentrations of total RNA in their blood than healthy individuals (Fig. 2A). In contrast, the levels of miR-361-3p was significantly decreased in NSCLC patients in comparison to healthy individuals (p = 0.0001) and patients with benign lung disease (p = 0.0001), whereas the levels of this miR were similar in healthy individuals and patients with benign lung disease (Fig. 2B). Surprisingly, the relative transcript levels of miR-625* was significant higher in serum of patients with benign lung disease than in healthy individuals (p = 0.0001) and NSCLC patients (p = 0.0001) (Fig. 2C). However, the levels of this miR were significantly lower in NSCLC than in benign disease (p = 0.0001) and healthy individuals (p = 0.0005, Fig. 2C).


Low levels of cell-free circulating miR-361-3p and miR-625* as blood-based markers for discriminating malignant from benign lung tumors.

Roth C, Stückrath I, Pantel K, Izbicki JR, Tachezy M, Schwarzenbach H - PLoS ONE (2012)

Evaluation of the diagnostic relevance of levels of total RNA and miRs in serum of healthy individuals, patients with benign lung disease and NSCLC patients.The box plots show the different, relative amounts of total RNA (A), miR-361-3p (B) and miR-625* (C) which circulate in blood of healthy individuals (n = 30), patients with benign lung disease (n = 20) and NSCLC patients (n = 97). The relative transcript levels of miRs were determined by the low cycle threshold (Ct) values. As determined by Mann and Whitney-U test, the significant p values of the statistical evaluations of serum RNA and miR levels are indicated. The ROC analysis shows the profile of sensitivity and specificity of miR-361-3p and miR-625* concentrations to discriminate NSCLC patients from patients with benign disease and healthy individuals (D). The AUC values and confidence intervals are indicated.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3366929&req=5

pone-0038248-g002: Evaluation of the diagnostic relevance of levels of total RNA and miRs in serum of healthy individuals, patients with benign lung disease and NSCLC patients.The box plots show the different, relative amounts of total RNA (A), miR-361-3p (B) and miR-625* (C) which circulate in blood of healthy individuals (n = 30), patients with benign lung disease (n = 20) and NSCLC patients (n = 97). The relative transcript levels of miRs were determined by the low cycle threshold (Ct) values. As determined by Mann and Whitney-U test, the significant p values of the statistical evaluations of serum RNA and miR levels are indicated. The ROC analysis shows the profile of sensitivity and specificity of miR-361-3p and miR-625* concentrations to discriminate NSCLC patients from patients with benign disease and healthy individuals (D). The AUC values and confidence intervals are indicated.
Mentions: The concentrations of miR-361-3p and miR-625* were further evaluated in blood serum of 97 NSCLC patients, 20 patients with benign lung disease and 30 healthy individuals. The box plots in Fig. 2 compare the relative levels of total RNA and miRs in healthy individuals and patients with benign or malignant lung disease. Patients with benign (p = 0.0001) and malignant disease (p = 0.0001) displayed significant higher concentrations of total RNA in their blood than healthy individuals (Fig. 2A). In contrast, the levels of miR-361-3p was significantly decreased in NSCLC patients in comparison to healthy individuals (p = 0.0001) and patients with benign lung disease (p = 0.0001), whereas the levels of this miR were similar in healthy individuals and patients with benign lung disease (Fig. 2B). Surprisingly, the relative transcript levels of miR-625* was significant higher in serum of patients with benign lung disease than in healthy individuals (p = 0.0001) and NSCLC patients (p = 0.0001) (Fig. 2C). However, the levels of this miR were significantly lower in NSCLC than in benign disease (p = 0.0001) and healthy individuals (p = 0.0005, Fig. 2C).

Bottom Line: Microarray profiling showed that miR-361-3p and miR-625* were significantly down-regulated in serum of lung cancer patients.Moreover, the levels of miR-625* were significantly lower in patients with large cell lung cancer (LCLC, p = 0.014) and smoking patients (p = 0.030) than in patients with adenocarcinoma and non-smoking patients, respectively.A rise in the levels of both miRs was observed in the postoperative samples compared with the preoperative levels (p = 0.0001).

View Article: PubMed Central - PubMed

Affiliation: Department of Tumor Biology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

ABSTRACT
The high mortality rate of lung cancer patients is mainly due to the late stage at which lung cancer is diagnosed. For effective cancer prevention programs and early diagnosis, better blood-based markers are needed. Hence, blood-based microarray profiling of microRNA (miR) expression was performed in preoperative serum of 21 non-small cell lung cancer (NSCLC) patients and 11 healthy individuals by microfluid biochips containing 1158 different miRs. Two out of the 30 most dysregulated miRs were further validated in serum of 97 NSCLC patients, 20 patients with benign lung diseases and 30 healthy individuals by TaqMan MicroRNA Assays. Microarray profiling showed that miR-361-3p and miR-625* were significantly down-regulated in serum of lung cancer patients. Their further evaluation by quantitative RT-PCR showed that the levels of miR-361-3p and miR-625* were lower in NSCLC than in benign disease (p = 0.0001) and healthy individuals (p = 0.0001, p = 0.0005, respectively). Moreover, the levels of miR-625* were significantly lower in patients with large cell lung cancer (LCLC, p = 0.014) and smoking patients (p = 0.030) than in patients with adenocarcinoma and non-smoking patients, respectively. A rise in the levels of both miRs was observed in the postoperative samples compared with the preoperative levels (p = 0.0001). Functional analyses showed that Smad2 and TGFß1 are not dysregulated by miR-361-3p and miR-625* in the lung cell line A549, respectively. Our present pilot study suggests that miR-361-3p and miR-625* might have a protective influence on the development of NSCLC, and the quantitative assessment of these miRs in blood serum might have diagnostic potential to detect NSCLC, in particular in smokers.

Show MeSH
Related in: MedlinePlus