Gene Expression Meta-Analysis Identifies VDAC1 as a Predictor of Poor Outcome in Early Stage Non-Small Cell Lung Cancer

The bioenergetic status of non-small cell lung cancer correlates with tumour aggressiveness. The voltage dependent anion channel type 1 (VDAC1) is a component of the mitochondrial permeability transition pore, regulates mitochondrial ATP/ADP exchange suggesting that its over-expression could be associated with energy dependent processes including increased proliferation and invasiveness. To test this hypothesis, we conducted an in vivo gene-expression meta-analysis of surgically resected non-small cell lung cancer (NSCLC) using 602 individual expression profiles, to examine the impact of VDAC1 on survival.High VDAC1 expression was associated with shorter overall survival with hazard ratio (HR) = 0.6639 (95% confidence interval (CI) 0.4528 to 0.9721), p = 0.035352 corresponding to 52 versus 101 months. VDAC1 predicted shorter time to recurrence and was shown to be an independent prognostic factor compared with histology, gender, age, nodal stage and tumour stage in a Cox multivariate analysis. Supervised analysis of all the datasets identified a 6-gene signature comprising HNRNPC, HSPA4, HSPA9, UBE2D2, CSNK1A1 and G3BP1 with overlapping functions involving regulation of protein turnover, RAS-RAF-MEK pathway and transcription. VDAC1 predicted survival in breast cancer and myeloma and an unsupervised analysis revealed enrichment of the VDAC1 signature in specific subsets.In summary, gene expression analysis identifies VDAC1 gene expression as a predictor of poor outcome in NSCLC and other cancers and is associated with dysregulation of a conserved set of biological pathways, which may be causally associated with aggressive tumour behaviour

A TMA De-Arraying Method for High Throughput Biomarker Discovery in Tissue Research

BACKGROUND: Tissue MicroArrays (TMAs) represent a potential high-throughput platform for the analysis and discovery of tissue biomarkers. As TMA slides are produced manually and subject to processing and sectioning artefacts, the layout of TMA cores on the final slide and subsequent digital scan (TMA digital slide) is often disturbed making it difficult to associate cores with their original position in the planned TMA map. Additionally, the individual cores can be greatly altered and contain numerous irregularities such as missing cores, grid rotation and stretching. These factors demand the development of a robust method for de-arraying TMAs which identifies each TMA core, and assigns them to their appropriate coordinates on the constructed TMA slide. METHODOLOGY: This study presents a robust TMA de-arraying method consisting of three functional phases: TMA core segmentation, gridding and mapping. The segmentation of TMA cores uses a set of morphological operations to identify each TMA core. Gridding then utilises a Delaunay Triangulation based method to find the row and column indices of each TMA core. Finally, mapping correlates each TMA core from a high resolution TMA whole slide image with its name within a TMAMap. CONCLUSION: This study describes a genuine robust TMA de-arraying algorithm for the rapid identification of TMA cores from digital slides. The result of this de-arraying algorithm allows the easy partition of each TMA core for further processing. Based on a test group of 19 TMA slides (3129 cores), 99.84% of cores were segmented successfully, 99.81% of cores were gridded correctly and 99.96% of cores were mapped with their correct names via TMAMaps. The gridding of TMA cores were also extensively tested using a set of 113 pseudo slide (13,536 cores) with a variety of irregular grid layouts including missing cores, rotation and stretching. 100% of the cores were gridded correctly

Mathematical and statistical modelling of apoptosis

EThOS - Electronic Theses Online ServiceGBUnited Kingdo

The World Health Organization Engaging with Civil Society Networks to Promote Primary Health Care : A Case Study

Engagement between the World Health Organization (WHO) and civil society organizations (CSOs), gains importance as CSOs increase their contribution to public health; particularly to primary health care. To better engage civil society in revitalizing primary health care the WHO collaborated with the Community Health Global Network (CHGN), a civil society network. This article uses the WHO-CHGN relationship to demonstrate how this collaboration enabled the WHO to inform and to learn from those with current primary health care experience. Learning from a systematic documentation of the collaboration provides insight into the WHO and CHGN perspectives concerning the relationship; informs future WHO-CSO collaborations and contributes to the understanding of the ways in which the WHO accesses and hears those actively engaged in health care programs.Peer reviewe

List of evaluation results for the 19 test cases from set .

<p><i>M(1)</i> refers to Manders' and <i>M(2)</i> refers to Manders' , they are multiplied by 100% to be comparable with our results.</p

Illustration of generic co-localisation.

<p>(A) the red object (top) and green object (bottom) are overlapped and co-localised at focal plane 2, (B) the red (top) object and green object (bottom) are not co-localised, however many co-localisation measurements would incorrectly recognise these as co-localisation.</p

List of evaluation results for the 10 test cases from set .

<p>σ(•) is the standard deviation for either CIC or CBC for all the focal planes in one stack of test case. <i>M(1)</i> refers to Manders' and <i>M(2)</i> refers to Manders' , they are multiplied by 100% to be comparable with our results.</p