The prognostic value of phosphorylated AKT expression in non-small cell lung cancer: a meta-analysis.

OBJECTIVES: Phosphorylated AKT (p-AKT), constitutive activation of AKT, is a potentially interesting prognostic marker and therapeutic target in non-small cell lung cancer (NSCLC). However, the available results of p-AKT expression in NSCLC are heterogeneous. Therefore, a meta-analysis of published researches investigating the prognostic relevance of p-AKT expression in patients with NSCLC was performed. MATERIALS AND METHODS: A literature search via PubMed, EMBASE and CNKI (China National Knowledge Infrastructure) databases was conducted. Data from eligible studies were extracted and included into meta-analysis using a random effects model. RESULTS: A total of 1049 patients from nine studies were included in the meta-analysis. Nine studies investigated the relationship between p-AKT expression and overall survival using univariate analysis, and five of these undertook multivariate analysis. The pooled hazard ratio (HR) for overall survival was 1.49 (95% confidence interval (CI): 1.01-2.20) by univariate analysis and 1.02 (95% CI: 0.54-1.95) by multivariate analysis. CONCLUSION: Our study shows that positive expression of p-AKT is associated with poor prognosis in patients with NSCLC. However, adequately designed prospective studies need to perform.

CD226 Gly307Ser association with multiple autoimmune diseases: a meta-analysis.

BACKGROUND: Recently, there has been increasing evidence shown that a non-synonymous exchange (Gly307Ser/rs763361) of the CD226 gene on chromosome 18q22 is linked to several autoimmune diseases (ADs) including type 1 diabetes (T1D), celiac disease (CED), rheumatoid arthritis (RA), multiple sclerosis (MS), Grave's disease, Wegener's granulomatosis (WG), psoriasis, and primary sicca syndrome (pSS). Taking into consideration that different autoimmune diseases may share some common pathogenic pathways and in order to assess the overall relationship between CD226 Gly307Ser (rs763361) polymorphism and multiple autoimmune diseases, we performed this meta-analysis. METHOD: All eligible case-control studies were searched in the US National Library of Medicine's PubMed and Embase database. Crude odds ratios (OR) with 95% confidence intervals (CI) were conducted to assess the association. RESULTS: 7876 cases and 8558 controls from 7 published studies which were selected from 149 articles identified by a search of the US National Library of Medicine's PubMed and Embase databases for the period up to 25th April 2012. The total OR for ADs associated with the T allele was 1.19 (95%CI=1.12-1.27) by random effects model. Significantly increased risks were also observed in the South American (OR=1.72, 95%CI=1.34-2.20), Asian (OR=1.46, 95%CI=1.01-2.10), and European (OR=1.29, 95%CI=1.07-1.58). Similarly, significant associations were observed in two genetic models (OR=1.41, 95%CI=1.23-1.62 in a codominant model; OR=1.33, 95%CI=1.18-1.50 in a recessive model). CONCLUSION: This meta-analysis provided evidence that CD226 Gly307Ser (rs763361) is significantly associated with the risk of multiple autoimmune diseases.

Prognostic impact of Raf-1 and p-Raf-1 expressions for poor survival rate in non-small cell lung cancer.

Overexpression of Raf-1 has commonly been observed in solid tumors including non-small cell lung cancer (NSCLC). The objective of this study was to investigate whether overexpression of Raf-1, phosphorylated-Raf-1 (p-Raf-1) or both correlates with poor survival rate in NSCLC patients and to explore associations between expression of these proteins and NSCLC cell fate both in vitro and in vivo. Expression of Raf-1 and p-Raf-1 were detected by immunohistochemistry in tumor specimens from 152 NSCLC patients and associations between their expression and the clinicopathological characteristics were assessed. Five-year median survival rate of patients were analyzed by Kaplan-Meier method, log-rank test and Cox regression. Cell fate was compared between normal tumor cells and those with Raf-1 silencing, in both the adenocarcinoma cell line A549 and xenografted mice that were infected with the A549 cell line. The incidence of overexpression of both Raf-1 and p-Raf-1 in NSCLC was much higher than normal control (P < 0.05), and the survival rate of patients with positive expression of Raf-1, p-Raf-1 or both was found to be significantly lower than the negative group (P < 0.05). Both univariate and multivariate analyses showed Raf-1 (P = 0.000, P = 0.010), p-Raf-1 (P = 0.004, P = 0.046), or both (P = 0.001, P = 0.016) was good prognostic markers for poor survival rate in NSCLC patients. Suppression of Raf-1 inhibited tumorigenesis by inducing apoptosis both in vitro and in vivo. These findings demonstrate that overexpression of Raf-1, p-Raf-1 or both could be considered as a new independent prognostic biomarker for poor survival rates for NSCLC patients.