Gene expression in fixed tissues and outcome in hepatocellular carcinoma

Yujin Hoshida, Augusto Villanueva, Masahiro Kobayashi, Judit Peix, Derek Y. Chiang, Amy Camargo, Supriya Gupta, Jamie Moore, Matthew J. Wrobel, Jim Lerner, Michael Reich, Jennifer A. Chan, Jonathan N. Glickman, Kenji Ikeda, Masaji Hashimoto, Goro Watanabe, Maria G. Daidone, Sasan Roayaie, Myron Schwartz, Swan ThungHelga B. Salvesen, Stacey Gabriel, Vincenzo Mazzaferro, Jordi Bruix, Scott L. Friedman, Hiromitsu Kumada, Josep M. Llovet, Todd R. Golub

Research output: Contribution to journalArticle

887 Scopus citations

Abstract

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tissue was highly effective: samples from 90% of the patients yielded data of high quality, including samples that had been archived for more than 24 years.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.

Original languageEnglish (US)
Pages (from-to)1995-2004
Number of pages10
JournalNew England Journal of Medicine
Volume359
Issue number19
DOIs
StatePublished - Nov 6 2008

ASJC Scopus subject areas

  • Medicine(all)

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    Hoshida, Y., Villanueva, A., Kobayashi, M., Peix, J., Chiang, D. Y., Camargo, A., Gupta, S., Moore, J., Wrobel, M. J., Lerner, J., Reich, M., Chan, J. A., Glickman, J. N., Ikeda, K., Hashimoto, M., Watanabe, G., Daidone, M. G., Roayaie, S., Schwartz, M., ... Golub, T. R. (2008). Gene expression in fixed tissues and outcome in hepatocellular carcinoma. New England Journal of Medicine, 359(19), 1995-2004. https://doi.org/10.1056/NEJMoa0804525