APRIL promotes non-small cell lung cancer growth and metastasis by targeting ERK1/2 signaling.

Non-small-cell lung cancer (NSCLC) is the major subtype of lung cancer, which is the most common cause of cancer-related mortality in the world. It is a complex disease involving multiple genetic alterations. As a cytokine belonging to the Tumor Necrosis Factor-α (TNF- α) family, the - a proliferation-inducing ligand (APRIL) expression and its signaling have been studied in many human solid tumor types, but the data on APRIL signaling in NSCLC are lacking. The aim of this study was to evaluate the APRIL expression and investigate its signaling in NSCLC. The expression of APRIL and its receptors, B cell maturation antigen (BCMA) and transmembrane activator and calcium-modulatorand cyclophilin ligand interactor (TACI), was analyzed by using immunohistochemistry in NSCLC samples. Quantitative RT-PCR was performed to evaluate mRNA expression of APRIL, BCMA and TACI in human lung adenocarcinoma cell lines A549, H1299, and H1650. Cell proliferation was measured by using the cell proliferation and cytotoxicity assay kit 8 (CCK8) assay, cell migration by using wound healing assay, and cell invasion by using transwall assay. The protein level of APRIL, BCMA and TAC, and the activation of extracellular regulated protein kinases 1/2 (ERK1/2) signaling, were determined by western blot. Our results indicated, APRIL and its receptors BCMA and TACI, were overexpressed in most of human NSCLC samples and cell lines; APRIL promoted tumor proliferation, migration and metastasis in A549 and H1299 cells via BCMA and TACI. Furthermore, ERK1/2 activation was involved in APRIL signaling through TACI but not BCMA in A549 and H1299 cells. APRIL might serve as a potential prognostic biomarker for NSCLC, and APRIL related signaling pathway could be a therapeutic target for NSCLC.

APRIL, BCMA and TACI proteins are abnormally expressed in non-small cell lung cancer.

Lung cancer is the leading cause of cancer-associated mortality. Non-small cell lung cancer (NSCLC) accounts for >80% of lung cancers. The overall survival for NSCLC is dismal, with a 5-year survival of <5% for patients. Thus, identifying an effective biomarker for early diagnosis of lung cancer is the first essential step to reduce mortality. It has been recognized that certain inflammatory and immune responses are important in lung cancer development and prevention. The present study demonstrated that, in NSCLC, a proliferation-inducing ligand (APRIL), B-cell maturation antigen (BCMA)and transmembrane activator and CAML interactor (TACI) proteins are abnormally expressed by immunohistochemistry, reverse transcription-quantitative polymerase chain reaction and western blotting. In addition, the expression of APRIL, BCMA and TACI were observed to be involved in extracellular signal-regulated kinase (ERK)1/2 activation in A549 cells. Overall, the present study provides evidence that APRIL and its receptors, BCMA and TACI, may play roles in the biological processes of NSCLC tumors through the ERK1/2 signaling pathway.

Decreased plasma let-7c and miR-152 as noninvasive biomarker for non-small-cell lung cancer.

BACKGROUND: Non-small-cell lung cancer (NSCLC) is one of the leading causes of death. The aim of the present study was to compare the expression of let-7c and miR-152 in surgically resected NSCLC cases and healthy cases to evaluate their diagnostic impact. METHODS: This hospital-based case-control study included 120 NSCLC patients and 360 healthy controls. The miRNA levels were measured via quantitative reverse transcription-polymerase chain reaction and their association with NSCLC was assessed by statistical data analysis and receiver operating characteristic curves. RESULTS: The expression of let-7c and miR-152 in plasma were found to be downregulated in the patients with NSCLC. Advanced studies showed that the plasma let-7c and miR-152 were correlated with the clinicopathological features such as histological classifications, differentiation status, lymph node metastasis and stage classifications. The ROC curves for the miRNAs revealed a strong diagnostic performance. ROC curve analyses revealed that both plasma let-7c and miR-152 could serve as valuable biomarkers for NSCLC cases from healthy controls with an AUC of 0.714 and 0.845. CONCLUSION: It was found that let-7c and miR-152 are significantly reduced in plasma samples of NSCLC patients. These findings suggest that detection of circulating let-7c and miR-152 can be developed into a noninvasive and rapid diagnostic tool for the individuals with NSCLC.

Meta-analysis: diagnostic accuracy of anti-cyclic citrullinated peptide antibody for juvenile idiopathic arthritis.

OBJECTIVE: To estimate the diagnostic accuracy of the anti-CCP test in JIA and to evaluate factors associated with higher accuracy. METHODS: Two investigators performed an extensive search of the literature published between January 2000 and January 2014. The included articles were assessed by the Quality Assessment of Diagnostic Accuracy Studies tool. The meta-analysis was performed using a summary ROC (SROC) curve and a bivariate random-effect model to estimate sensitivity and specificity across studies. RESULTS: The bivariate meta-analysis yielded a pooled sensitivity and specificity of 10% (95% confidence interval (CI): 6.0%-15.0%) and 99.0% (95% CI: 98.0%-100.0%). The area under the SROC curve was 0.96. Sensitivity estimates were highly heterogeneous, which was partially explained by the higher sensitivity in the rheumatoid factor-positive polyarthritis (RF+ PA) subtype (48.0%; 95% CI: 31.0%-65.0%) than in the other subtypes (17.0%; 95% CI: 14.0%-20.0%) and the higher sensitivity of the Inova assay (17.0%; 95% CI: 14.0%-20.%%) than the other assays (0.05%; 95% CI: 2.0%-11.0%). CONCLUSIONS: Anti-CCP antibody test has a high specificity for the diagnosis of JIA. The sensitivity of this test is low and varies across populations but is higher in RF+ PA than in other JIA subtypes.

Diagnostic accuracy of fecal lactoferrin for inflammatory bowel disease: a meta-analysis.

OBJECTIVE: To do a systematic review using meta-analysis to assess the diagnostic accuracy of fecal lactoferrin (FL) in patients with inflammatory bowel disease (IBD). METHODS: We performed a literature review and systematically searched the Medline and EMBASE databases for eligible studies. The quality of the included studies was assessed using the QUADAS tool. The sensitivity, specificity, and other diagnostic indexes of FL were pooled using a random-effects model. RESULTS: Seven studies, involving 1816 patients, met the inclusion criteria. In all studies, the pooled FL sensitivity and pooled specificity were 0.82 (95% confidence interval [CI]: 0.72, 0.89) and 0.95 (95% CI: 0.88, 0.98), respectively. The positive and negative likelihood ratios were 16.63 and 0.18, respectively. The area under the summary receiver-operating characteristic curve (SROC) was 0.95 (95% CI: 0.93, 0.97), and the diagnostic odds ratio was 90.04 (95% CI: 37.01, 219.02). The pooled FL sensitivity and specificity for Crohn's disease (CD) diagnosis (sensitivity =75%, specificity =100%) was not as good as it was for ulcerative colitis (UC) diagnosis (sensitivity =82%, specificity =100%). CONCLUSION: FL, as a noninvasive and screening marker, has a high specificity and a modest specificity during the diagnosis of suspected IBD.

The angiotensin-converting enzyme (ACE) I/D polymorphism in Parkinson's disease.

OBJECTIVE: The angiotensin-converting enzyme (ACE) may be involved in the pathogenesis of Parkinson's disease (PD). There have been several studies investigating the association between ACE gene I/D polymorphism and PD risk, but they reported inconsistent findings. We performed a meta-analysis to investigate the association between ACE gene I/D polymorphism and PD risk. METHODS: Published literature from PubMed and Embase databases were searched for eligible publications. Pooled odds ratios (ORs) with 95% confidence intervals (95% CIs) were calculated using random- or fixed-effects models based on between-study heterogeneity. RESULTS: A total of five studies including 606 cases and 708 controls were finally included in the meta-analysis. Meta-analysis showed that there was no obvious association between ACE gene I/D polymorphism and PD risk under the homogeneous co-dominant model (OR = 1.14, 95% CI = 0.71-1.82), heterogeneous co-dominant model (OR = 0.92, 95% CI = 0.70-1.22), dominant model (OR = 0.99, 95% CI = 0.76-1.28) or recessive model (OR = 1.07, 95% CI = 0.83-1.37). CONCLUSION: The meta-analysis suggests that there is no evidence for the association between ACE gene I/D polymorphism and PD risk.

Hepatitis C virus infection and the risk of Sjögren or sicca syndrome: a meta-analysis.

Previous studies have suggested an association between hepatitis C virus (HCV) infection and the development of Sjögren's syndrome (SS), also known as sicca syndrome. The main objective of this study was to summarize the existing evidence and quantitatively evaluate the association between hepatitis C virus infection and SS/sicca syndrome by performing a meta-analysis of observational studies. MEDLINE and PubMed (January 1980-August 2013) were searched to identify relevant studies in English. Outcomes were calculated and are reported as odds risk (OR) and 95% CIs based on a random-effects model. Heterogeneity was assessed with I(2) statistics. Quality assessment was performed with the Newcastle-Ottawa scale. Based on meta-analysis of five cross-sectional and five cohort studies, a significant positive relationship between HCV infection and development of SS/sicca syndrome was found, the pooled random effects OR being 3.31 (95% CI, 1.46-7.48; P < 0.001). In subset analyses, the studies that used European diagnostic criteria showed a higher summary OR than did studies that adopted other diagnostic criteria. When the data were stratified by source of controls, significant associations were also observed when healthy people (OR = 9.44; 95% CI = 2.67-33.40; P = 0.204) or subjects with hepatitis B virus infection (OR = 6.57; 95% CI = 1.21-35.57; P = 0.5) were used as controls, but not when the controls were hospital-based (OR = 0.99; 95% CI = 0.61-1.61; P = 0.169). In summary, the findings suggest that HCV infection is associated with SS/sicca syndrome. The observed increased risk in studies in which European diagnostic criteria and healthy controls were used and the decreased risk in studies with hospital-based controls may be attributable to selection bias or other unknown factors.

Development of a colloidal gold-based immunochromatographic test strip for the rapid, on-site detection of Pseudomonas aeruginosa in clinical samples.

BACKGROUND: Current procedures for the detection of Pseudomonas aeruginosa require sophisticated equipment, skilled technicians, and a great deal of time. Immunochromatography assays (ICA) are simple and rapid diagnostic procedures that can be performed and interpreted on the spot or at the bedside without a machine. METHODS: We developed a rapid, 1-step immunochromatographic test strip that is well suited to the on-site detection of P. aeruginosa with high sensitivity and specificity. In brief, a monoclonal antibody targeting the outer membrane protein F (OprF) of P. aeruginosa, 3C3B5, was conjugated to colloidal gold and used as a detection antibody. An OprF polyclonal antibody was developed as the capture antibody. Eighty-three clinical samples were examined for P. aeruginosa by rapid 1-step ICA and compared with Multiplex-polymerase chain reaction (M-PCR). RESULTS: The detection limit of this method is 5 × 10(5) CFU/ml for P. aeruginosa and 10 ng/ml for the OprF protein. The immunochromatographic strip test demonstrated a slightly lower sensitivity (84.8%), but a similar specificity (100%), to multi-PCR, which is an accurate method for the detection of P. aeruginosa in the laboratory. We observed no cross-reactivity with non-P. aeruginosa bacterial microbes. The detection of P. aeruginosa by the ICA strip can be completed within 5-10 min and is at least 10-fold faster than M-PCR. CONCLUSIONS: The ICA test strip developed in this study has proved to be a rapid, simple, effective and economical method for the detection of P. aeruginosa infection in clinical samples. To our knowledge, this is the first report of an ICA method being used to detect P. aeruginosa.