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Conservation of gene expression signatures between zebrafish and human liver tumors and tumor progression

Abstract

The zebrafish (Danio rerio) has been long advocated as a model for cancer research, but little is known about the real molecular similarities between zebrafish and human tumors. Comparative analysis of microarray data from zebrafish liver tumors with those from four human tumor types revealed molecular conservation at various levels between fish and human tumors. This approach provides a useful strategy for identifying an expression signature that is strongly associated with a disease phenotype.

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Figure 1: Venn diagrams showing the intersections between zebrafish ZLTDEGS and the human liver, gastric, prostate and lung tumor microarray data sets.
Figure 2: Expression profiles of 132 genes showing similar correlation with tumor progression in both zebrafish and human liver tumors (LGDN, low-grade dysplastic nodule; HGDN, high-grade dysplastic nodule; G1–G3, grade 1–3).

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Acknowledgements

We thank S.Y. Neo, S.W. Nam and J.Y. Lee for the human liver cancer data sets. This work is supported by the BioMedical Research Council, Singapore, US Public Health Service Grants ES011587, ES03850, ES00210 and RR12546.

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Correspondence to Zhiyuan Gong.

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The authors declare no competing financial interests.

Supplementary information

Supplementary Fig. 1

Zebrafish liver tumors and normal liver. (PDF 331 kb)

Supplementary Table 1

Functional category of selected genes that are significantly differentially expressed in zebrafish liver tumor. (XLS 42 kb)

Supplementary Table 2

Gene Set Enrichment Analysis (GSEA) and Binomial Test Probability (P) value of Zebrafish Liver Tumor Differentially Expressed Gene Set (ZLTDEGS) in human liver, gastric, prostate and lung data set. (XLS 22 kb)

Supplementary Table 3

Conserved expression signature (126 genes) between zebrafish and human liver tumors. (XLS 48 kb)

Supplementary Table 4

Conserved expression signature (76 genes) between zebrafish and human liver tumors that is more consistently associated with human liver tumor than human gastric, prostate and lung tumor types as indicated by the FDR adjusted P-values. (XLS 38 kb)

Supplementary Table 5

Selected Genes (63) from Zebrafish Liver Tumor Differentially Expressed Gene Set (ZLTDEGS) validated by quantitative Real-Time PCR and confirmed to be significant (P<0.05) with one tail, heterocedastic Student's T-Test. (XLS 31 kb)

Supplementary Methods (DOC 70 kb)

Supplementary Data (XLS 960 kb)

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Lam, S., Wu, Y., Vega, V. et al. Conservation of gene expression signatures between zebrafish and human liver tumors and tumor progression. Nat Biotechnol 24, 73–75 (2006). https://doi.org/10.1038/nbt1169

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