Low levels of cell-free circulating miR-361-3p and miR-625* as blood-based markers for discriminating malignant from benign lung tumors.
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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, Carina; Stückrath, Isabel; Pantel, Klaus; Izbicki, Jakob R.; Tachezy, Michael; Schwarzenbach, Heidi.
in: PLOS ONE, Jahrgang 7, Nr. 6, 6, 2012, S. 38248.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Low levels of cell-free circulating miR-361-3p and miR-625* as blood-based markers for discriminating malignant from benign lung tumors.
AU - Roth, Carina
AU - Stückrath, Isabel
AU - Pantel, Klaus
AU - Izbicki, Jakob R.
AU - Tachezy, Michael
AU - Schwarzenbach, Heidi
PY - 2012
Y1 - 2012
N2 - 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.
AB - 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.
KW - Adult
KW - Humans
KW - Aged
KW - Middle Aged
KW - Aged, 80 and over
KW - Cohort Studies
KW - Reproducibility of Results
KW - Reverse Transcriptase Polymerase Chain Reaction
KW - Gene Expression Regulation, Neoplastic
KW - Oligonucleotide Array Sequence Analysis
KW - Gene Expression Profiling
KW - Postoperative Care
KW - Preoperative Care
KW - Carcinoma, Non-Small-Cell Lung/blood/diagnosis/genetics/surgery
KW - Cell-Free System
KW - Health
KW - Lung Neoplasms/blood/diagnosis/genetics/surgery
KW - MicroRNAs/blood/genetics/metabolism
KW - Smad2 Protein/metabolism
KW - Smoking/genetics
KW - Transforming Growth Factor beta1/genetics/metabolism
KW - Tumor Markers, Biological/blood/genetics
KW - Adult
KW - Humans
KW - Aged
KW - Middle Aged
KW - Aged, 80 and over
KW - Cohort Studies
KW - Reproducibility of Results
KW - Reverse Transcriptase Polymerase Chain Reaction
KW - Gene Expression Regulation, Neoplastic
KW - Oligonucleotide Array Sequence Analysis
KW - Gene Expression Profiling
KW - Postoperative Care
KW - Preoperative Care
KW - Carcinoma, Non-Small-Cell Lung/blood/diagnosis/genetics/surgery
KW - Cell-Free System
KW - Health
KW - Lung Neoplasms/blood/diagnosis/genetics/surgery
KW - MicroRNAs/blood/genetics/metabolism
KW - Smad2 Protein/metabolism
KW - Smoking/genetics
KW - Transforming Growth Factor beta1/genetics/metabolism
KW - Tumor Markers, Biological/blood/genetics
U2 - 10.1371/journal.pone.0038248
DO - 10.1371/journal.pone.0038248
M3 - SCORING: Journal article
VL - 7
SP - 38248
JO - PLOS ONE
JF - PLOS ONE
SN - 1932-6203
IS - 6
M1 - 6
ER -
