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Identification of a three-miRNA signature as a blood-borne diagnostic marker for early diagnosis of lung adenocarcinoma.

Oncotarget. 2016 Mar 27;

Authors: Wang Y, Zhao H, Gao X, Wei F, Zhang X, Su Y, Wang C, Li H, Ren X

Abstract
BACKGROUND: The subtypes of NSCLC have unique characteristics of pathogenic mechanism and responses to targeted therapies. Thus, non-invasive markers for diagnosis of different subtypes of NSCLC at early stage are needed.
RESULTS: Based on the results from the screening and validation process, 3 miRNAs (miR-532, miR-628-3p and miR-425-3p) were found to display significantly different expression levels in early-stage lung adenocarcinoma, as compared to those in healthy controls. ROC analysis showed that the miRNA-based biomarker could distinguish lung adenocarcinoma from healthy controls with high AUC (0.974), sensitivity (91.5%), and specificity (97.8%). Importantly, these three miRNAs could also distinguish lung adenocarcinoma from lung benigh diseases and other subtypes of lung cancer.
METHODS: Two hundreds and one early-stage lung adenocarcinoma cases and one hundreds seventy eight age- and sex-matched healthy controls were recruited to this study. We screened the differentially expressed plasma miRNAs using TaqMan Low Density Arrays (TLDA) followed by three-phase qRT-PCR validation. A risk score model was established to evaluate the diagnostic value of the plasma miRNA profiling system.
CONCLUSIONS: Taken together, these findings suggest that the 3 miRNA-based biomarker might serve as a novel non-invasive approach for diagnosis of early-stage lung adenocarcinoma.

PMID: 27036025 [PubMed - as supplied by publisher]

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Tuberculosis is the leading infectious cause of death worldwide, with 9·6 million cases and 1·5 million deaths reported in 2014. WHO estimates 480 000 cases of these were multidrug resistant (MDR). Less than half of patients who entered into treatment for MDR tuberculosis successfully completed that treatment, mainly due to high mortality and loss to follow-up. These in turn illustrate weaknesses in current treatment regimens and national tuberculosis programmes, coupled with operational treatment challenges.

In this Review we provide an update on recent developments in the tuberculosis drug-development pipeline (including new and repurposed antimicrobials and host-directed drugs) as they are applied to new regimens to shorten and improve outcomes of tuberculosis treatment. Several new or repurposed antimicrobial drugs are in advanced trial stages for MDR tuberculosis, and two new antimicrobial drug candidates are in early-stage trials. Several trials to reduce the duration of therapy in MDR and drug-susceptible tuberculosis are ongoing. A wide range of candidate host-directed therapies are being developed to accelerate eradication of infection, prevent new drug resistance, and prevent permanent lung injury. As these drugs have been approved for other clinical indications, they are now ready for repurposing for tuberculosis in phase 2 clinical trials. We assess risks associated with evaluation of new treatment regimens, and highlight opportunities to advance tuberculosis research generally through regulatory innovation in MDR tuberculosis. Progress in tuberculosis-specific biomarkers (including culture conversion, PET and CT imaging, and gene expression profiles) can support this innovation.

Several global initiatives now provide unique opportunities to tackle the tuberculosis epidemic through collaborative partnerships between high-income countries and middle-income and low-income countries for clinical trials training and research, allowing funders to coordinate several national and regional programmes for greatest overall effect.

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BACKGROUND AND OBJECTIVE: We conducted a systematic review and meta-analysis to compare the accuracy of the interferon-gamma release assays (IGRAs) and the tuberculin skin test (TST) for the diagnosis of Mycobacterium tuberculosis infection.

METHODS: We systematically searched PubMed, Embase, Cochrane library, and Web of Science databases for relevant published studies in recent decades and calculated pooled estimated sensitivities, specificities, DOR, and SROC curve of the QFT-IT, T-SPOT and TST. Random-effects models were used to assess estimates from studies with significant heterogeneity. Moreover, area under the curve was used to evaluate the accuracy of the tests.

RESULTS: Overall, 9 studies for QFT-IT, 12 studies for T-SPOT, and 16 studies for TST involving 3586 participants were included in this analysis. We found that sensitivities of the QFT-IT, T-SPOT, and TST were respectively 0.842 (95 % CI 0.811-0.870), 0.840 (95 % CI 0.814-0.864), and 0.665 (CI 0.635-0.693); specificities were respectively 0.745 (95 % CI 0.715-0.775), 0.658 (95 % CI 0.621-0.693), and 0.633 (CI 0.605-0.661); positive likelihood ratios were respectively 3.652 (95 % CI 2.180-6.117), 2.196 (95 % CI 1.727-2.794), and 1.825 (95 % CI 1.351-2.464); negative likelihood ratios were respectively 0.212 (95 % CI 0.109-0.414), 0.246 (95 % CI 0.161-0.377), and 0.556 (95 % CI 0.385-0.804); the SROC curves were 19.205, 10.397, and 3.810.

CONCLUSIONS: The two IGRAs showed better performance than TST for the diagnosis of the tuberculosis. However, neither of them showed stability in the diagnosis of TB.