title: Individualized identification of disease-associated pathways with disrupted coordination of gene expression.
abstract: Current pathway analysis approaches are primarily dedicated to capturing deregulated pathways at the population level and cannot provide patient-specific pathway deregulation information. In this article, the authors present a simple approach, called individPath, to detect pathways with significantly disrupted intra-pathway relative expression orderings for each disease sample compared with the stable, normal intra-pathway relative expression orderings pre-determined in previously accumulated normal samples. Through the analysis of multiple microarray data sets for lung and breast cancer, the authors demonstrate individPath's effectiveness for detecting cancer-associated pathways with disrupted relative expression orderings at the individual level and dissecting the heterogeneity of pathway deregulation among different patients. The portable use of this simple approach in clinical contexts is exemplified by the identification of prognostic intra-pathway gene pair signatures to predict overall survival of resected early-stage lung adenocarcinoma patients and signatures to predict relapse-free survival of estrogen receptor-positive breast cancer patients after tamoxifen treatment.
authors.forename: Hongwei
authors.initials: H
authors.lastname: Wang
authors.forename: Hao
authors.initials: H
authors.lastname: Cai
authors.forename: Lu
authors.initials: L
authors.lastname: Ao
authors.forename: Haidan
authors.initials: H
authors.lastname: Yan
authors.forename: Wenyuan
authors.initials: W
authors.lastname: Zhao
authors.forename: Lishuang
authors.initials: L
authors.lastname: Qi
authors.forename: Yunyan
authors.initials: Y
authors.lastname: Gu
authors.forename: Zheng
authors.initials: Z
authors.lastname: Guo
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000401:mortality; D000077192:Adenocarcinoma of Lung; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality; D019295:Computational Biology / Q000379:methods; D030541:Databases, Genetic / Q000706:statistics & numerical data; D018572:Disease-Free Survival; D005260:Female; D020869:Gene Expression Profiling / Q000706:statistics & numerical data; D015972:Gene Expression Regulation, Neoplastic; D020022:Genetic Predisposition to Disease; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000235:genetics* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy / Q000235:genetics / Q000401:mortality; D020411:Oligonucleotide Array Sequence Analysis / Q000706:statistics & numerical data; D057285:Precision Medicine / Q000379:methods / Q000706:statistics & numerical data; D011379:Prognosis; D013629:Tamoxifen / Q000627:therapeutic use
chemical_list: D018931:Antineoplastic Agents, Hormonal; D013629:Tamoxifen
keywords: individualized pathway; relative expression orderings; stable/reversal gene pair