BACKGROUND: It is a challenge to identify patients who, after undergoing potentially curative treatment for hepatocellular carcinoma, are at greatest risk for recurrence. Such high-risk patients could receive novel interventional measures. An obstacle to the development of genome-based predictors of outcome in patients with hepatocellular carcinoma has been the lack of a means to carry out genomewide expression profiling of fixed, as opposed to frozen, tissue. METHODS: We aimed to demonstrate the feasibility of gene-expression profiling of more than 6000 human genes in formalin-fixed, paraffin-embedded tissues. We applied the method to tissues from 307 patients with hepatocellular carcinoma, from four series of patients, to discover and validate a gene-expression signature associated with survival. RESULTS: The expression-profiling method for formalin-fixed, paraffin-embedded tissue was highly effective: samples from 90% of the patients yielded data of high quality, including samples that had been archived for more than 24 years. Gene-expression profiles of tumor tissue failed to yield a significant association with survival. In contrast, profiles of the surrounding nontumoral liver tissue were highly correlated with survival in a training set of tissue samples from 82 Japanese patients, and the signature was validated in tissues from an independent group of 225 patients from the United States and Europe (P=0.04). CONCLUSIONS: We have demonstrated the feasibility of genomewide expression profiling of formalin-fixed, paraffin-embedded tissues and have shown that a reproducible gene-expression signature correlated with survival is present in liver tissue adjacent to the tumor in patients with hepatocellular carcinoma. Copyright 2008 Massachusetts Medical Society.
BACKGROUND: It is a challenge to identify patients who, after undergoing potentially curative treatment for hepatocellular carcinoma, are at greatest risk for recurrence. Such high-risk patients could receive novel interventional measures. An obstacle to the development of genome-based predictors of outcome in patients with hepatocellular carcinoma has been the lack of a means to carry out genomewide expression profiling of fixed, as opposed to frozen, tissue. METHODS: We aimed to demonstrate the feasibility of gene-expression profiling of more than 6000 human genes in formalin-fixed, paraffin-embedded tissues. We applied the method to tissues from 307 patients with hepatocellular carcinoma, from four series of patients, to discover and validate a gene-expression signature associated with survival. RESULTS: The expression-profiling method for formalin-fixed, paraffin-embedded tissue was highly effective: samples from 90% of the patients yielded data of high quality, including samples that had been archived for more than 24 years. Gene-expression profiles of tumor tissue failed to yield a significant association with survival. In contrast, profiles of the surrounding nontumoral liver tissue were highly correlated with survival in a training set of tissue samples from 82 Japanese patients, and the signature was validated in tissues from an independent group of 225 patients from the United States and Europe (P=0.04). CONCLUSIONS: We have demonstrated the feasibility of genomewide expression profiling of formalin-fixed, paraffin-embedded tissues and have shown that a reproducible gene-expression signature correlated with survival is present in liver tissue adjacent to the tumor in patients with hepatocellular carcinoma. Copyright 2008 Massachusetts Medical Society.
Authors: T Takayama; T Sekine; M Makuuchi; S Yamasaki; T Kosuge; J Yamamoto; K Shimada; M Sakamoto; S Hirohashi; Y Ohashi; T Kakizoe Journal: Lancet Date: 2000-09-02 Impact factor: 79.321
Authors: Jian-Bing Fan; Joanne M Yeakley; Marina Bibikova; Eugene Chudin; Eliza Wickham; Jing Chen; Dennis Doucet; Philippe Rigault; Baohong Zhang; Richard Shen; Celeste McBride; Hai-Ri Li; Xiang-Dong Fu; Arnold Oliphant; David L Barker; Mark S Chee Journal: Genome Res Date: 2004-05 Impact factor: 9.043
Authors: Marina Bibikova; Dimitri Talantov; Eugene Chudin; Joanne M Yeakley; Jing Chen; Dennis Doucet; Eliza Wickham; David Atkins; David Barker; Mark Chee; Yixin Wang; Jian-Bing Fan Journal: Am J Pathol Date: 2004-11 Impact factor: 4.307
Authors: K Ikeda; Y Arase; S Saitoh; M Kobayashi; Y Suzuki; F Suzuki; A Tsubota; K Chayama; N Murashima; H Kumada Journal: Hepatology Date: 2000-08 Impact factor: 17.425
Authors: Josep M Llovet; Adrian M Di Bisceglie; Jordi Bruix; Barnett S Kramer; Riccardo Lencioni; Andrew X Zhu; Morris Sherman; Myron Schwartz; Michael Lotze; Jayant Talwalkar; Gregory J Gores Journal: J Natl Cancer Inst Date: 2008-05-13 Impact factor: 13.506
Authors: Andrea Sboner; Francesca Demichelis; Stefano Calza; Yudi Pawitan; Sunita R Setlur; Yujin Hoshida; Sven Perner; Hans-Olov Adami; Katja Fall; Lorelei A Mucci; Philip W Kantoff; Meir Stampfer; Swen-Olof Andersson; Eberhard Varenhorst; Jan-Erik Johansson; Mark B Gerstein; Todd R Golub; Mark A Rubin; Ove Andrén Journal: BMC Med Genomics Date: 2010-03-16 Impact factor: 3.063