ROC analysis of miRNA expression.

<p>Receiving Operator Characteristic (ROC) curves for individual miRNAs and combination of miR-19b and miR-183. (A)–(E) Individual miRNAs; (F) Binary logistic regression of miR-19b and miR-183. ROC curves discriminate squamous cell carcinoma (SCC), adenocarcinoma (AD) and total study population of lung cancer patients (LC) from healthy individuals (HD).</p

MiRNA expression in age groups.

<p>Box plots of relative miRNA expression levels in plasma of lung cancer patients divided into three age groups: <60 years, 60–70 years, >70 years. The expression levels of miRNAs were normalized to miR-16 using dCq method. *P = 0.004; **P = 0.007 (One-way ANOVA).</p

Plasma miR-19b and miR-183 as Potential Biomarkers of Lung Cancer

<div><p>Lung cancer is a complex disease that often manifests at the point when treatment is not effective. Introduction of blood-based complementary diagnostics using molecular markers may enhance early detection of this disease and help reduce the burden of lung cancer. Here we evaluated the diagnostic potential of seven plasma miRNA biomarkers (miR-21, -19b, -126, -25, -205, -183, -125b) by quantitative reverse transcription PCR. Influence clinical and demographical characteristics, including age, tumor stage and cancer subtype on miRNA levels was investigated. Four miRNAs were significantly dysregulated (miR-19b, -21, -25, -183) in lung cancer patients. Combination of miR-19b and miR-183 provided detection of lung cancer with 94.7% sensitivity and 95.2% specificity (AUC = 0.990). Thus, miRNAs have shown the potential to discriminate histological subtypes of lung cancer and reliably distinguish lung cancer patients from healthy individuals.</p></div

Targets and functions of selected miRNAs.

<p>Targets and functions of selected miRNAs.</p

Dynamic changes in circulating miRNA levels in response to antitumor therapy of lung cancer

<p><b>Purpose:</b> Expression levels of cancer-associated microRNAs were reported to be altered in serum/plasma samples from lung cancer patients compared with healthy subjects. The purpose of this study was to estimate the value of five selected miRNAs plasma levels as markers of response to antitumor therapy in lung cancer patients. <b>Materials and Methods:</b> Expression levels of miR-19b, miR-126, miR-25, miR-205, and miR-125b have been evaluated by quantitative reverse transcription PCR versus control miR-16 in blood plasma samples from 23 lung cancer (LC) patients. Plasma samples were obtained from LC patients before treatment (untreated-UT), within 30 days after completing two courses of chemotherapy (postchemotherapy-PC) and 15 days after surgery (postoperative-PO). <b>Results:</b> Repeated Measures ANOVA demonstrated that miR-19b expression levels were decreased in PC and increased in PO samples. These changes were characterized by a significant quadratic trend (<i>p</i> = 0.03). Expression levels of miR-125b increased both after chemotherapy and again after surgery and demonstrated a significant linear trend (<i>p</i> = 0.03). The miR-125b/miR-19b ratio changed during the course of the antitumor treatment with a significant linear trend (<i>p</i> = 0.04). Individual analysis in the groups of patients with partial response to chemotherapy and patients with stable or progressive disease showed different trends for miR-19b, miR-125b, and miR-125b/miR-19b ratio between the groups. The Kaplan–Meier survival curves demonstrated an association of miR-125b/miR-19b ratio value with the survival time without the tumor relapse (<i>p</i> < 0.1). <b>Conclusions:</b> Dynamic change of trends for miR-19b and miR-125b expression levels and miR-125b/miR-19b ratio in the blood plasma have shown a potentiality to discriminate types of response to antitumor therapy in lung cancer patients. Further in-depth investigation is needed to establish a direct link the miRNAs expression levels in blood plasma with therapy response and patient's survival.</p

Survival analysis of LC patients.

<p>Kaplan-Meier survival analysis of lung cancer patients. (A)–(D) Expression of miRNAs and survival of lung cancer patients. The ‘High’ and ‘Low’ miRNA expression groups were delimited by group median dCq value for each miRNA.</p

Overview of the study population.

<p>Overview of the study population.</p