期刊
NEW ENGLAND JOURNAL OF MEDICINE
卷 359, 期 19, 页码 1995-2004出版社
MASSACHUSETTS MEDICAL SOC
DOI: 10.1056/NEJMoa0804525
关键词
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资金
- National Institute of Diabetes and Digestive and Kidney Diseases [1R01DK076986-01]
- National Cancer Institute [5U54 CA112962-03]
- Samuel Waxman Cancer Research Foundation
- Spanish National Health Institute [SAF2007-61898]
- Institucio Catalana de Recerca i Estudis Avancats
- Centro de Investigaciones en Red de Enfermedades Hepaticas y Digestivas
- Fund for Health of Spain of the Institute of Health Carlos III [PI05-0150]
- National Institutes of Health [DK37340]
- Italian Association for Cancer Research
- Norwegian Cancer Society
- Harald Andersens grant
- Charles A. King Trust fellowship
- Fundacion Pedro Barri, de la Maza
- Sheila Sherlock Fellowship
- National Cancer Center Fellowship
- ICREA Funding Source: Custom
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tissue was highly effective: samples from 90% of the patients yielded data of high quality, including samples that had been archived for more than 24 years.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.
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