Identification of a prognostic 5-Gene expression signature for gastric cancer
JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY
Authors: Hou, Jun-Yi; Wang, Yu-Gang; Ma, Shi-Jie; Yang, Bing-Yin; Li, Qian-Ping
Abstract
Gastric cancer (GC) is a major tumor throughout the world with remaining high morbidity and mortality. The aim is to generate a gene model to assess the prognoses risk of patients with GC. Gene expression profiling of gastric cancer patients, GSE62254 (300 samples) and GSE26253 (432 samples), was downloaded from Gene Expression Omnibus (GEO) database. Univariate survival analysis and LASSO (Least Absolute Shrinkage and Selectionator operator) (1000 iterations) of differentially expressed genes in GSE62254 was assessed using survival and glmnet in R package, respectively. Kaplan-Meier analysis on the clustering algorithm from each regression model was performed to calculate the influence to the prognosis. Random samples in GSE26253 were analyzed in multivariate and univariate survival analysis for one thousand times to calculate statistical stability of each regression model. A total of 854 Genes were identified differentially expressed in GSE62254, among which 367 Genes were found influencing the prognoses. Six gene clusters were selected with good stability. Hereinto, five or more genes in 11-Gene model, TRPC1, SGCE, TNFRSF11A, LRRN1, HLF, CYS1, PPP1R14A, NOV, NBEA, CES1 and RGN, was available to evaluate the prognostic risk of GC patients in GSE26253 (P = 0.00445). The validity and reliability was validated. In conclusion, we successfully generated a stable 5-Gene model, which could be utilized to predict prognosis of GC patients and would contribute to postoperational treatment and follow-up strategies.
Cumulative Meta-Analysis for Genetic Association: When Is a New Study Worthwhile?
HUMAN HEREDITY
Authors: Rotondi, Michael A.; Bull, Shelley B.
Abstract
Objectives: In this paper, we address the questions: how large a sample size would be required to show genome-wide significance between a single nucleotide polymorphism (SNP) and a genetic trait in a meta-analysis of a newly planned study together with the existing ones? Or alternatively: will a planned study of size n be able to provide evidence of a genetic association when this study is combined with a current meta-analysis? Methods: We examine the potential impact of a newly planned genetic study on an existing meta-analysis through the use of a simulation-based algorithm. The proposed approach provides an empirical estimate of the power of the updated meta-analysis to detect genome-wide significance (p < 5.0 x 10(-8)) of a complex trait and each of a set of specific SNPs of interest or the expected p value of the updated meta-analysis including the current and proposed studies. Results: This technique is illustrated in the context of an updated meta-analysis of case-control studies in Paget's disease. A second example illustrates the impact of adding a newly planned study to a large meta-analysis of SNP associations with human height. Conclusions: The proposed algorithm is particularly useful for the design of studies to assess a selected set of high-priority SNP associations that are 'nearly' significant in meta-analysis of existing studies. The results may help investigators decide whether an updated meta-analysis is likely to achieve genome-wide significance. Copyright (c) 2012 S. Karger AG, Basel