Identification of serum MiRNAs as candidate biomarkers for non-small cell lung cancer diagnosis.

BACKGROUND: Lung cancer is one of the most common solid tumors worldwide and the leading cause of cancer-associated death. Non-small cell lung cancer (NSCLC) is accounts for approximately 85% of all the lung cancers and lung squamous carcinoma (SCC) and adenocarcinoma (ADC) are the main subtypes of NSCLC. Early diagnose using serum biomarkers could improve the overall survival of patients. In this study, we aimed to identify miRNAs from serum with clinical utility in the diagnosis of NSCLC. METHODS: Ten patients with SCC, ten patients with ADC and five noncancerous individuals were enrolled in the screening cohort. miRNA expression levels in serum were measured by microarray analysis. Candidate miRNAs were validated by real-time quantitative polymerase chain reaction analysis in a validation cohort of 78 NSCLC patients and 44 noncancerous individuals. Receiver operating characteristic curves were used to assess the diagnostic performance of serum miRNAs for NSCLC. Logistic regression was used to evaluate the diagnostic value of the combination of markers. RESULTS: Six candidate miRNAs were differentially expressed between NSCLC patients and noncancerous individuals in the screening set (fold change > 2, p < 0.05). Among them, expression levels of miR-3149 and miR-4769.3p were confirmed to be significantly increased in tumor serum in the validation set. The area under the curve values of miR-3149 and miR-4769.3p in distinguishing NSCLC patients from noncancerous controls were 0.830 and 0.735, respectively. When combined with tumor markers CEA and Cyfra21-1, the joint diagnostic model increased the area under the curve to 0.898. CONCLUSION: Serum miRNAs miR-3149 and miR-4769.3p were up-regulated in NSCLC and may be potential biomarkers for early diagnosis of lung cancer.

The isocitrate dehydrogenase 1 is a potential prognostic indicator for non-small cell lung cancer patients.

BACKGROUND: The serum isocitrate dehydrogenase 1(IDH1) level is significantly elevated in patients with non-small cell lung cancer (NSCLC) and has important clinical value as a marker for early diagnosis. This study examined the dynamic changes of serum IDH1 levels of patients with NSCLC undergoing surgery or medical treatment, to evaluate its potential prognostic value. METHODS: The study cohort included 83 NSCLC patients who underwent surgery, 37 NSCLC patients who underwent medical treatment, 50 healthy controls, and 52 disease controls. Serum levels of IDH1 were assayed by enzyme-linked immunoassay. Tumor biomarkers including carcinoembryonic antigen, squamous cell carcinoma, neuron-specific enolase, CYFRA21-1, and pro-gastrin-releasing peptide-which are currently used in clinical practice-were measured by automatic immunoanalyzers. RESULTS: Serum IDH1 was significantly higher in patients with NSCLC compared with healthy people or patients with benign lung diseases (p < 0.001). The area under the receiver operating characteristic curve for diagnosis and differential diagnosis were 0.897 and 0.879, respectively, which were superior to the five tumor markers. Serum IDH1 levels decreased in most patients after surgery, with the most dramatic changes in patients with stage I tumors compared with stage II and III. Analyses of changes in the serum IDH1 level of patients after receiving chemotherapy or targeted therapy revealed that for patients with progressive disease, serum IDH1 increased significantly after treatment; for patients with partial response or stable disease, it decreased steadily. CONCLUSION: IDH1 has potential prognostic value and may be used as a marker for the monitoring of treatment efficacy.

The Clinical Significance of Serum MASP-2 and IDH1 in the Early Diagnosis of Non-Small Cell Lung Cancer.

BACKGROUND: The lack of effective means for the early diagnosis of non-small cell lung cancer (NSCLC) is the leading cause of the high mortality of NSCLC. This study aims to evaluate the clinical significance of serum mannan-binding lectin associated serine protease (MASP)-2 and isocitrate dehydrogenase 1 (IDH1) in the early diagnosis of NSCLC. METHODS: The serum levels of MASP-2 and IDH1 were detected in 139 NSCLC patients, 46 patients with benign lung diseases and 61 healthy controls, using an enzyme linked immunosorbent method. The diagnostic significance in NSCLC of the two tumor markers were analyzed by receiver operating characteristic (ROC) curves. In addition, we compared the two markers with the current commonly used tumor marker cytokeratin 19 fragment (Cy¬fra21-1). RESULTS: The serum levels of MASP-2 and IDH1 in the NSCLC patients were significantly higher than those of healthy controls and patients with benign lung diseases. The differences were statistically significant (p < 0.01). The combined sensitivity of MASP-2, IDH1, and Cyfra21-1 in the NSCLC was 68.3%, which was significantly higher than that of the single tumor marker (p < 0.01). The sensitivities of MASP-2 and IDH1 in detecting early NSCLC (stage I and stage II) were 39.0% and 41.5%, which were significantly higher than that of Cyfra21-1 (p < 0.05). The area under the ROC curves (AUCs) of MASP-2 and IDH1 in the diagnosis of NSCLC were 0.621, and 0.840, which were higher than that of Cyfra21-1 (AUC = 0.606). CONCLUSIONS: Serum MASP-2 and IDH1 may be used as potential tumor markers for the auxiliary diagnosis and early diagnosis of NSCLC.

Prognostic Significance of Serum miR-22, miR-125b, and miR-15b in Non-Small Cell Lung Cancer Patients.

BACKGROUND: Studies have shown that miRNA (miR) can be stably detected in serum, and aberrant expression of various miRNAs has shown diagnostic value in non-small cell lung cancer (NSCLC) patients. However, the role of miRNA in the context of prognosis has not been extensively investigated. Our previous study reported that miR-22, miR-125b, and miR-15b in serum had potential for use as tumor markers for auxiliary diagnosing of NSCLC. Therefore, the objective of this study was to detect the levels of miR-22, miR-125b, and miR-15b in serum from NSCLC patients and explore the potential prognostic significance of the three selected miRNAs. METHODS: The relative expression of miR-22, miR-125b, and miR-15b in 74 patients with advanced NSCLC in pre- and post-chemotherapy were detected by real-time quantitative polymerase chain reaction. RESULTS: Serum level of miR-125b significantly decreased after chemotherapy (p < 0.05) and the levels of miR-15b significantly increased (p < 0.01), while there was no change in the level of serum miR-22 (Z = 0.716, p > 0.05). Compared with pre-chemotherapy, serum miR-125b expression in advanced NSCLC patients of responders (CR + PR) were significantly decreased post-chemotherapy (p < 0.05); serum miR-15b expression in advanced NSCLC patients of responders (CR + PR) were increased (p < 0.01). The chemotherapy sensitivity of advanced NSCLC patients with high expression of miR-125b was lower than that of NSCLC patients with low expression (p < 0.05). The chemotherapy sensitivity of advanced NSCLC patients with high expression of miR-15b was higher than that of NSCLC patients with low expression (p < 0.05). High levels of serum miR-125b and low levels of serum miR-15b were related to poor overall survival (p < 0.05). CONCLUSIONS: The serum levels of miR-125b and miR-15b in advanced NSCLC patients were changed pre- and post-chemotherapy and these changes were associated with chemotherapeutic response. Serum miR-125b and miR-15b have certain potential clinical value for chemotherapeutic response in advanced NSCLC. The serum levels of miR-125b and miR-15b in patients with advanced NSCLC before treatment may be used to estimate the overall survival.