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E-GEOD-10140 - Gene Expression in Fixed Tissues and Outcome in Hepatocellular Carcinoma (Training Set, Liver)

Status
Submitted on 10 January 2008, released on 18 May 2010, last updated on 1 May 2014
Organism
Homo sapiens
Samples (82)
Array (1)
Protocols (7)
Description
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tissue was highly effective: samples from 90% of the patients yielded data of high quality, including samples that had been archived for more than 24 years.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.
Experiment type
transcription profiling by array 
Contacts
Yujin Hoshida <hoshida@broad.mit.edu>, Amy Camargo, Augusto Villanueva, Derek Chiang, Goro Watanabe, Hiromitsu Kumada, Jamie Moore, Jennifer A Chan, Jim Lerner, Jordi Bruix, Josep M Llovet, Judit Peix, Kenji Ikeda, Masahiro Kobayashi, Masashi Hashimoto, Matthew J Wrobel, Michael Reich, Myron Schwartz, Sasan Roayaie, Scott Friedman, Stacey Gabriel, Supriya Gupta, Swan Thung, Todd R Golub, Vincenzo Mazzaferro
Citation
Gene expression in fixed tissues and outcome in hepatocellular carcinoma. Hoshida Y, Villanueva A, Kobayashi M, Peix J, Chiang DY, Camargo A, Gupta S, Moore J, Wrobel MJ, Lerner J, Reich M, Chan JA, Glickman JN, Ikeda K, Hashimoto M, Watanabe G, Daidone MG, Roayaie S, Schwartz M, Thung S, Salvesen HB, Gabriel S, Mazzaferro V, Bruix J, Friedman SL, Kumada H, Llovet JM, Golub TR.
MIAME
PlatformsProtocolsVariablesProcessedRaw
Files
Investigation descriptionE-GEOD-10140.idf.txt
Sample and data relationshipE-GEOD-10140.sdrf.txt
Raw data (1)E-GEOD-10140.raw.1.zip
Processed data (1)E-GEOD-10140.processed.1.zip
Experiment designE-GEOD-10140.biosamples.png, E-GEOD-10140.biosamples.svg
Array designA-GEOD-5474.adf.txt
Links