Serum microRNAs have been identified as potential cancer biomarkers. However, the detailed mechanism by which expression of microRNAs contributes to the development and diagnosis of NSCLC remains unknown. This study was to identify specific miRNAs for diagnosing or predicting the prognosis of NSCLC patients and their correlation between miRNA expression in tissues and serums. Six matched cancer and noncancerous tissues from NSCLC patients were analyzed by miRNA microarray. Among these, three miRNAs (miR-21, miR-141, and miR-200c) were examined in 70 NSCLC paired samples (cancer, normal tissue, and serum) and 44 serum samples of normal volunteers by quantitative reverse transcription polymerase chain reaction (qRT-PCR). Consisting with the microarray results, the expression levels of miR-21, miR-141, and miR-200c in NSCLC were higher than those in normal tissues. While the level of serum miR-21 was increased in cancer patients as compared with that in normal counterpart, expression of miR-141 and miR-200c showed lower levels in serums from cancer patients. Overexpression of serum miR-21 was strongly associated with lymph node metastasis and advanced clinical stage of NSCLC. Finally, log-rank and Cox regression tests demonstrated that high expressions of tumor miR 21 and miR-200c or serum miR-21 were associated with a poor survival in NSCLC patients. Our results suggest that tumor miR-21, miR-141, miR-200c, and serum miR-21 may be potential novel biomarkers for the diagnosis of NSCLC. In addition, this study, for the first time, identifies a significant role of the tumor miR-200c played in predicting prognosis in patients with NSCLC.

BackgroundAltered 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).MethodsmiRNA 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.ResultsLevels 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.ConclusionsThe 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.

Blood-circulating miRNAs could be useful as a biomarker to detect lung cancer early. We investigated the serum levels of four different miRNAs in patients with non-small cell lung cancer (NSCLC) and assessed their diagnostic value for NSCLC. Serum samples from 112 NSCLC patients and 104 controls (20 current smokers without lung cancer, 23 pneumonia patients, 21 gastric cancer patients, and 40 healthy controls) were subjected to Taqman probe-based quantitative reverse transcription–polymerase chain reaction (RT-PCR). The data showed that the serum levels of miR-182, miR-183, and miR-210 were significantly upregulated and that the miR-126 level was significantly downregulated in NSCLC patients, compared with the healthy controls. Further receiver operating characteristic (ROC) curve analysis revealed that the serum miR-182, miR-183, miR-210, or miR-126 level could serve as a diagnostic biomarker for NSCLC early detection, with a high sensitivity and specificity. The combination of these four miRNAs with carcinoembryonic antigen (CEA) further increased the diagnostic value, with an area under the curve (AUC) of 0.965 (sensitivity, 81.3%; specificity, 100.0%; and accuracy, 90.8%) using logistic regression model analysis. In addition, the relative levels of serum miR-182, miR-183, miR-210, and miR-126 could distinguish NSCLC or early-stage NSCLC from current tobacco smokers without lung cancer and pneumonia or gastric cancer patients with a high sensitivity and specificity. Data from the current study validated that the four serum miRNAs could serve as a tumor biomarker for NSCLC early diagnosis.

BackgroundLung cancer is the leading cause of cancer-related deaths worldwide. Early detection is considered critical for lung cancer treatment. MicroRNAs (miRNAs) have shown promise as diagnostic and prognostic indicators. This study was to identify specific miRNAs with diagnostic and prognostic value for patients with lung cancer, and to explore the correlation between expression profiles of miRNAs and patient survival.MethodsGene expression of members of the miR-183 family (miR-96, miR-182, and miR-183) were examined in 70 paired samples from lung cancer patients (primary cancer and non-cancerous tissues and sera), as well as 44 serum samples from normal volunteers and lung cancer cell lines by quantitative real-time reverse transcription polymerase chain reaction (RT-qPCR). The correlation between the expression of miRNAs in tissues, sera, and patient overall survival were also examined by log-rank and Cox regression analysis.ResultsExpression levels of members of the miR-183 family in lung cancer tumor and sera were higher than that of their normal counterparts. The miR-96 expression in tumors was positively associated with its expression in sera. Log-rank and Cox regression analyses demonstrated that high expression of tumor and serum miRNAs of the miR-183 family were associated with overall poor survival in patients with lung cancer.ConclusionsOur results suggest that the expressions of miR-96, miR-182, and miR-183 in tumor and sera may be considered potential novel biomarkers for the diagnosis and prognosis of lung cancer.

Although circulating microRNAs (miRNAs) were frequently detected in sera of cancer patients, there is still a lack of analysis of the dynamic changes of miRNAs expression in sera of pre- and post-operative lung carcinoma patients. Thus, we conducted quantitative reverse transcription-polymerase chain reaction (qRT-PCR) to examine the expression of four miRNAs (miR-21, miR-205, miR-30d, and miR-24) in the sera of a set of 82 pre-operative lung carcinoma patients and paired 10 days post-operative patients, as well as in 50 normal volunteers. We showed that, compared to that in normal volunteers, the expression of miR-21, miR-205, miR-30d, and miR-24 was increased in lung cancer sera samples, as well as in sera of early stage lung cancer patients according to their clinical-pathological characteristics. The area under roc curves (AUCs) for levels of miR-21, miR-205, miR-30d, and miR-24 in sera were significantly higher than those for Carcinoma embryonic antigen (CEA) (P < 0.05), whereas the AUC for combination of serum levels of miRNA with serum CEA showed no significant difference from that for serum levels of miRNAs only (P > 0.05). The expression levels of miR-21 and miR-24 were significantly decreased in post-operative sera compared with levels in paired pre-operative sera (P = 0.0004 and <0.0001, respectively). In addition, high expressions of miR-21 and miR-30d in pre-operative sera were independently correlated with shorter overall survival in lung cancer patients (log-rank test: P = 0.0498, 0.0019). In summary, our results suggest that miR-21, miR-205, miR-30d, and miR-24 may serve as potential novel non-invasive biomarkers for diagnosis of lung cancer. In addition, miR-21 and miR-24 serum levels were lower in post-operative samples than those in pre-operative samples, suggesting they can potentially be used as biomarkers for disease recurrence after surgery operation.

Lung cancer is the leading cause of cancer-related deaths worldwide and non-small cell lung cancer (NSCLC) accounts for over 80% of lung cancer cases. The RNA binding protein, QKI, belongs to the STAR family and plays tumor-suppressive functions in NSCLC. QKI-5 is a major isoform of QKIs and is predominantly expressed in NSCLC. However, the underlying mechanisms of QKI-5 in NSCLC progression remain unclear. We found that QKI-5 regulated microRNA (miRNA), miR-196b-5p, and its expression was significantly up-regulated in NSCLC tissues. Up-regulated miR-196b-5p promotes lung cancer cell migration, proliferation, and cell cycle through directly targeting the tumor suppressors, GATA6 and TSPAN12. Both GATA6 and TSPAN12 expressions were down-regulated in NSCLC patient tissue samples and were negatively correlated with miR-196b-5p expression. Mouse xenograft models demonstrated that miR-196b-5p functions as a potent onco-miRNA, whereas TSPAN12 functions as a tumor suppressor in NSCLC in vivo. QKI-5 bound to miR-196b-5p and influenced its stability, resulting in up-regulated miR-196b-5p expression in NSCLC. Further analysis showed that hypomethylation in the promoter region enhanced miR-196b-5p expression in NSCLC. Our findings indicate that QKI-5 may exhibit novel anticancer mechanisms by regulating miRNA in NSCLC, and targeting the QKI5∼miR-196b-5p∼GATA6/TSPAN12 pathway may enable effectively treating some NSCLCs.

Using DNA microarrays, we generated both mRNA and miRNA expression data from 6 non-small cell lung cancer (NSCLC) tissues and their matching normal control from adjacent tissues to identify potential miRNA markers for diagnostics. We demonstrated that hsa-miR-96 is significantly and consistently up-regulated in all 6 NSCLCs. We validated this result in an independent set of 35 paired tumors and their adjacent normal tissues, as well as their sera that are collected before surgical resection or chemotherapy, and the results suggested that hsa-miR-96 may play an important role in NSCLC development and has great potential to be used as a noninvasive marker for diagnosing NSCLC. We predicted potential miRNA target mRNAs based on different methods (TargetScan and miRanda). Further classification of miRNA regulated genes based on their relationship with miRNAs revealed that hsa-miR-96 and certain other miRNAs tend to down-regulate their target mRNAs in NSCLC development, which have expression levels permissive to direct interaction between miRNAs and their target mRNAs. In addition, we identified a significant correlation of miRNA regulation with genes coincide with high density of CpG islands, which suggests that miRNA may represent a primary regulatory mechanism governing basic cellular functions and cell differentiations, and such mechanism may be complementary to DNA methylation in repressing or activating gene expression.

In an environment of frequent high Genotype B or C viremia, blood donors vaccinated at birth are frequently but mildly infected: asymptomatic and normal alanine aminotransferase level, identified by anti-HBc seroconversion and boosting of anti-HBs. Low viral load and frequent anti-HBs limit transfusion risk.