Reverse Engineering of Modified Genes by Bayesian Network Analysis Defines Molecular Determinants Critical to the Development of Glioblastoma

In this study we have identified key genes that are critical in development of astrocytic tumors. Meta-analysis of microarray studies which compared normal tissue to astrocytoma revealed a set of 646 differentially expressed genes in the majority of astrocytoma. Reverse engineering of these 646 genes using Bayesian network analysis produced a gene network for each grade of astrocytoma (Grade I–IV), and ‘key genes’ within each grade were identified. Genes found to be most influential to development of the highest grade of astrocytoma, Glioblastoma multiforme were: COL4A1, EGFR, BTF3, MPP2, RAB31, CDK4, CD99, ANXA2, TOP2A, and SERBP1. All of these genes were up-regulated, except MPP2 (down regulated). These 10 genes were able to predict tumor status with 96–100% confidence when using logistic regression, cross validation, and the support vector machine analysis. Markov genes interact with NFkβ, ERK, MAPK, VEGF, growth hormone and collagen to produce a network whose top biological functions are cancer, neurological disease, and cellular movement. Three of the 10 genes - EGFR, COL4A1, and CDK4, in particular, seemed to be potential ‘hubs of activity’. Modified expression of these 10 Markov Blanket genes increases lifetime risk of developing glioblastoma compared to the normal population. The glioblastoma risk estimates were dramatically increased with joint effects of 4 or more than 4 Markov Blanket genes. Joint interaction effects of 4, 5, 6, 7, 8, 9 or 10 Markov Blanket genes produced 9, 13, 20.9, 26.7, 52.8, 53.2, 78.1 or 85.9%, respectively, increase in lifetime risk of developing glioblastoma compared to normal population. In summary, it appears that modified expression of several ‘key genes’ may be required for the development of glioblastoma. Further studies are needed to validate these ‘key genes’ as useful tools for early detection and novel therapeutic options for these tumors.

The influence of neighbourhood formality status and socio-economic position on self-rated health among adult men and women: a multilevel, cross sectional, population study from Aleppo, Syria

Background There is substantial evidence from high income countries that neighbourhoods have an influence on health independent of individual characteristics. However, neighbourhood characteristics are rarely taken into account in the analysis of urban health studies from developing countries. Informal urban neighbourhoods are home to about half of the population in Aleppo, the second largest city in Syria (population>2.5 million). This study aimed to examine the influence of neighbourhood socioeconomic status (SES) and formality status on self-rated health (SRH) of adult men and women residing in formal and informal urban neighbourhoods in Aleppo. Methods The study used data from 2038 survey respondents to the Aleppo Household Survey, 2004 (age 18–65 years, 54.8% women, response rate 86%). Respondents were nested in 45 neighbourhoods. Five individual-level SES measures, namely education, employment, car ownership, item ownership and household density, were aggregated to the level of neighbourhood. Multilevel regression models were used to investigate associations. Results We did not find evidence of important SRH variation between neighbourhoods. Neighbourhood average of household item ownership was associated with a greater likelihood of reporting excellent SRH in women; odds ratio (OR) for an increase of one item on average was 2.3 (95% CI 1.3-4.4 (versus poor SRH)) and 1.7 (95% CI 1.1-2.5 (versus normal SRH)), adjusted for individual characteristics and neighbourhood formality. After controlling for individual and neighbourhood SES measures, women living in informal neighbourhoods were less likely to report poor SRH than women living in formal neighbourhoods (OR= 0.4; 95% CI (0.2- 0.8) (versus poor SRH) and OR=0.5; 95%; CI (0.3-0.9) (versus normal SRH). Conclusions Findings support evidence from high income countries that certain characteristic of neighbourhoods affect men and women in different ways. Further research from similar urban settings in developing countries is needed to understand the mechanisms by which informal neighbourhoods influence women’s health.