Transcriptomics

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Gene Expression in Fixed Tissues and Outcome in Hepatocellular Carcinoma (Training Set, Liver)


ABSTRACT: Background: It is a challenge to identify those patients who, after undergoing potentially curative treatments for hepatocellular carcinoma, are at greatest risk of 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, tissues. 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tissue was highly effective: samples from 90% of the patients yielded data of high quality, including samples that had been archived for more than 24 years.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 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 correlating with survival is present in liver tissue adjacent to the tumor in patients with hepatocellular carcinoma. Keywords: Hepatocellular carcinoma, Expression array, Illumina, Signatures, Outcome prediction Training cohort: 80 tumor and 82 non-tumor liver tissues surgically resected from patients with hepatocellular carcinoma (HCC); Validation cohort: 225 non-tumor liver tissues surgically resected from patients with HCC. Clinical data has been withheld from GEO due to privacy concerns.

ORGANISM(S): Homo sapiens  

SUBMITTER: Masashi Hashimoto  Hiromitsu Kumada   Michael Reich   Matthew J Wrobel   Augusto Villanueva   Jordi Bruix   Stacey Gabriel   Masahiro Kobayashi   Yujin Hoshida   Goro Watanabe   Jim Lerner   Jamie Moore   Amy Camargo   Judit Peix   Swan Thung   Todd R Golub   Scott Friedman   Josep M Llovet   Kenji Ikeda   Myron Schwartz   Jennifer A Chan   Supriya Gupta   Vincenzo Mazzaferro   Sasan Roayaie   Derek Chiang    

PROVIDER: E-GEOD-10140 | ArrayExpress | 2010-05-18

SECONDARY ACCESSION(S): GSE10140PRJNA108985

REPOSITORIES: GEO, ArrayExpress

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Publications


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.We aimed to demonstrate the feasibility of gene-  ...[more]

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