PURPOSE: We report a novel analytic method, named intercohort co-analysis or Ican, which aids in the discovery of genes with predictive value for the progression or outcome of diseases from small-size cohorts. We tested this premise in Ewing's sarcoma (ES), a highly metastatic cancer of bone and soft tissues that lacks validated molecular metastasis and prognostic indicators. EXPERIMENTAL DESIGN: To uncover genes significantly expressed in ES patient subsets, we first determined a nonarbitrary gene expression significance cutoff based on expression levels in validated expressing and nonexpressing tissues. We next searched for genes that were consistently significantly expressed in several ES cohort and cell line datasets. Significantly expressed genes were independently validated by quantitative reverse transcription-PCR in an additional ES cohort. RESULTS: Analysis of ES cohorts revealed marked intercohort gene expression variability. After filtering out the intercohort variability, CXCR4 and CXCR7 were found to be consistently associated with specific ES subsets. Pairwise analyses showed CXCR4 to correlate with ES metastases, and CXCR4 and CXCR7 to patient survival, but not with several other clinicopathological variables. CONCLUSION: Ican is a powerful novel method to identifying genes consistently associated with particular disease states in cancers for which large cohorts are not available, currently the case of most cancers. We report for the first time that high CXCR4 expression preferentially associates with metastatic ES, and that of CXCR7 with poor patient survival. Copyright 2010 AACR.
PURPOSE: We report a novel analytic method, named intercohort co-analysis or Ican, which aids in the discovery of genes with predictive value for the progression or outcome of diseases from small-size cohorts. We tested this premise in Ewing's sarcoma (ES), a highly metastatic cancer of bone and soft tissues that lacks validated molecular metastasis and prognostic indicators. EXPERIMENTAL DESIGN: To uncover genes significantly expressed in ES patient subsets, we first determined a nonarbitrary gene expression significance cutoff based on expression levels in validated expressing and nonexpressing tissues. We next searched for genes that were consistently significantly expressed in several ES cohort and cell line datasets. Significantly expressed genes were independently validated by quantitative reverse transcription-PCR in an additional ES cohort. RESULTS: Analysis of ES cohorts revealed marked intercohort gene expression variability. After filtering out the intercohort variability, CXCR4 and CXCR7 were found to be consistently associated with specific ES subsets. Pairwise analyses showed CXCR4 to correlate with ES metastases, and CXCR4 and CXCR7 to patient survival, but not with several other clinicopathological variables. CONCLUSION: Ican is a powerful novel method to identifying genes consistently associated with particular disease states in cancers for which large cohorts are not available, currently the case of most cancers. We report for the first time that high CXCR4 expression preferentially associates with metastatic ES, and that of CXCR7 with poor patient survival. Copyright 2010 AACR.
Authors: Sooryanarayana Varambally; Jianjun Yu; Bharathi Laxman; Daniel R Rhodes; Rohit Mehra; Scott A Tomlins; Rajal B Shah; Uma Chandran; Federico A Monzon; Michael J Becich; John T Wei; Kenneth J Pienta; Debashis Ghosh; Mark A Rubin; Arul M Chinnaiyan Journal: Cancer Cell Date: 2005-11 Impact factor: 31.743
Authors: Aravind Subramanian; Pablo Tamayo; Vamsi K Mootha; Sayan Mukherjee; Benjamin L Ebert; Michael A Gillette; Amanda Paulovich; Scott L Pomeroy; Todd R Golub; Eric S Lander; Jill P Mesirov Journal: Proc Natl Acad Sci U S A Date: 2005-09-30 Impact factor: 11.205
Authors: Tanya Barrett; Dennis B Troup; Stephen E Wilhite; Pierre Ledoux; Dmitry Rudnev; Carlos Evangelista; Irene F Kim; Alexandra Soboleva; Maxim Tomashevsky; Kimberly A Marshall; Katherine H Phillippy; Patti M Sherman; Rolf N Muertter; Ron Edgar Journal: Nucleic Acids Res Date: 2008-10-21 Impact factor: 16.971
Authors: Zhenhua Miao; Kathryn E Luker; Bretton C Summers; Rob Berahovich; Mahaveer S Bhojani; Alnawaz Rehemtulla; Celina G Kleer; Jeffrey J Essner; Aidas Nasevicius; Gary D Luker; Maureen C Howard; Thomas J Schall Journal: Proc Natl Acad Sci U S A Date: 2007-09-26 Impact factor: 11.205
Authors: Vivek Subbiah; Pete Anderson; Alexander J Lazar; Emily Burdett; Kevin Raymond; Joseph A Ludwig Journal: Curr Treat Options Oncol Date: 2009-06-17
Authors: Patrick J Leavey; Leo Mascarenhas; Neyssa Marina; Zhengjia Chen; Mark Krailo; James Miser; Ken Brown; Nancy Tarbell; Mark L Bernstein; Linda Granowetter; Mark Gebhardt; Holcombe E Grier Journal: Pediatr Blood Cancer Date: 2008-09 Impact factor: 3.167
Authors: Douglas F Easton; Karen A Pooley; Alison M Dunning; Paul D P Pharoah; Deborah Thompson; Dennis G Ballinger; Jeffery P Struewing; Jonathan Morrison; Helen Field; Robert Luben; Nicholas Wareham; Shahana Ahmed; Catherine S Healey; Richard Bowman; Kerstin B Meyer; Christopher A Haiman; Laurence K Kolonel; Brian E Henderson; Loic Le Marchand; Paul Brennan; Suleeporn Sangrajrang; Valerie Gaborieau; Fabrice Odefrey; Chen-Yang Shen; Pei-Ei Wu; Hui-Chun Wang; Diana Eccles; D Gareth Evans; Julian Peto; Olivia Fletcher; Nichola Johnson; Sheila Seal; Michael R Stratton; Nazneen Rahman; Georgia Chenevix-Trench; Stig E Bojesen; Børge G Nordestgaard; Christen K Axelsson; Montserrat Garcia-Closas; Louise Brinton; Stephen Chanock; Jolanta Lissowska; Beata Peplonska; Heli Nevanlinna; Rainer Fagerholm; Hannaleena Eerola; Daehee Kang; Keun-Young Yoo; Dong-Young Noh; Sei-Hyun Ahn; David J Hunter; Susan E Hankinson; David G Cox; Per Hall; Sara Wedren; Jianjun Liu; Yen-Ling Low; Natalia Bogdanova; Peter Schürmann; Thilo Dörk; Rob A E M Tollenaar; Catharina E Jacobi; Peter Devilee; Jan G M Klijn; Alice J Sigurdson; Michele M Doody; Bruce H Alexander; Jinghui Zhang; Angela Cox; Ian W Brock; Gordon MacPherson; Malcolm W R Reed; Fergus J Couch; Ellen L Goode; Janet E Olson; Hanne Meijers-Heijboer; Ans van den Ouweland; André Uitterlinden; Fernando Rivadeneira; Roger L Milne; Gloria Ribas; Anna Gonzalez-Neira; Javier Benitez; John L Hopper; Margaret McCredie; Melissa Southey; Graham G Giles; Chris Schroen; Christina Justenhoven; Hiltrud Brauch; Ute Hamann; Yon-Dschun Ko; Amanda B Spurdle; Jonathan Beesley; Xiaoqing Chen; Arto Mannermaa; Veli-Matti Kosma; Vesa Kataja; Jaana Hartikainen; Nicholas E Day; David R Cox; Bruce A J Ponder Journal: Nature Date: 2007-06-28 Impact factor: 49.962
Authors: Melanie A Krook; Lauren A Nicholls; Christopher A Scannell; Rashmi Chugh; Dafydd G Thomas; Elizabeth R Lawlor Journal: Mol Cancer Res Date: 2014-03-20 Impact factor: 5.852
Authors: Elisabeth A Pedersen; Rajasree Menon; Kelly M Bailey; Dafydd G Thomas; Raelene A Van Noord; Jenny Tran; Hongwei Wang; Ping Ping Qu; Antje Hoering; Eric R Fearon; Rashmi Chugh; Elizabeth R Lawlor Journal: Cancer Res Date: 2016-06-30 Impact factor: 12.701
Authors: E Guillemot; B Karimdjee-Soilihi; E Pradelli; M Benchetrit; E Goguet-Surmenian; M-A Millet; F Larbret; J-F Michiels; D Birnbaum; P Alemanno; H Schmid-Antomarchi; A Schmid-Alliana Journal: Br J Cancer Date: 2012-11-20 Impact factor: 7.640
Authors: Neerav Shukla; Joshua Schiffman; Damon Reed; Ian J Davis; Richard B Womer; Stephen L Lessnick; Elizabeth R Lawlor Journal: Front Oncol Date: 2013-06-06 Impact factor: 6.244
Authors: Dagmar Berghuis; Marco W Schilham; Susy J Santos; Suvi Savola; Helen J Knowles; Uta Dirksen; Karl-Ludwig Schaefer; Jukka Vakkila; Pancras Cw Hogendoorn; Arjan C Lankester Journal: Clin Sarcoma Res Date: 2012-12-18