Volume 42, Issue 6, Pages 860-869 (June 2005) Global gene repression in hepatocellular carcinoma and fetal liver, and suppression of dudulin-2 mRNA as a possible marker for the cirrhosis-to-tumor transition  Cédric Coulouarn, Céline Derambure, Grégory Lefebvre, Romain Daveau, Martine Hiron, Michel Scotte, Arnaud François, Maryvonne Daveau, Jean-Philippe Salier  Journal of Hepatology  Volume 42, Issue 6, Pages 860-869 (June 2005) DOI: 10.1016/j.jhep.2005.01.027 Copyright © 2005 European Association for the Study of the Liver Terms and Conditions

Fig. 1 Similarities and differences in mRNA levels regulated in early, late FL and/or HCCs vs controls. The diagrams depict the numbers of mRNAs whose levels were found to be up- or down-regulated in a given condition vs controls (A) or in a similar or opposite direction between conditions (B). A given mRNA was included whenever it was found to be regulated in at least the early or late FL or at least three out of nine HCC samples as compared to its average value in four control adult livers, as determined by microarray. In A, the total number of mRNAs is only 1436, for redundancy between subsets. Journal of Hepatology 2005 42, 860-869DOI: (10.1016/j.jhep.2005.01.027) Copyright © 2005 European Association for the Study of the Liver Terms and Conditions

Fig. 2 Clustering of liver sources by PCA. The 1436 mRNA levels found to be significantly up- or down-regulated in at least early or late FL (open square) or three HCCs (closed triangle 1–9) as compared to their mean level in control livers (open dot 1–4), i.e. the 1436 mRNAs in Fig. 1A, were used for PCA. The axes depict the first three variance components of the mRNAs included in the analysis, which together represent 84.9% of the total variance. Journal of Hepatology 2005 42, 860-869DOI: (10.1016/j.jhep.2005.01.027) Copyright © 2005 European Association for the Study of the Liver Terms and Conditions

Fig. 3 Clustering of samples or mRNAs by bi-dimensional hierarchical clustering. The 425 mRNAs found to be significantly regulated in at least early FL or late FL, as well as in at least three HCC samples as compared to their mean level in controls, i.e. the 425 mRNAs in Fig. 1B, were used for bi-dimensional hierarchical clustering (average linkage option). The samples are clustered horizontally and the mRNAs are clustered vertically (the gene symbols are omitted). In every sample a change (fold) in a given mRNA level relative to its mean level in the four control samples is shown as a colored bar of variable intensity (scale at the bottom). Subsets I or II contain mRNAs that are, respectively, down- or up-regulated in late FL and HCCs. Subset III contains mRNAs that are down-regulated in early FL, late FL and HCCs. Journal of Hepatology 2005 42, 860-869DOI: (10.1016/j.jhep.2005.01.027) Copyright © 2005 European Association for the Study of the Liver Terms and Conditions

Fig. 4 q-RT-PCR of dudulin-2 mRNA. The patients are all those listed in Table 1. All values (bar: mean) are expressed as a percent of the highest abundance (100%) found in one of the samples (C, control liver; CIR, cirrhosis; T, tumor). ES1-4 refers to the tumor differentiation grade 1–4 [46]. The Student's t test for two samples was used for comparison of any group vs the control patients (⋆, P<0.05; $, P<0.01). The Wilcoxon's matched-pairs signed ranks test was used for comparisons of paired samples (significance noted above an horizontal bracket). Journal of Hepatology 2005 42, 860-869DOI: (10.1016/j.jhep.2005.01.027) Copyright © 2005 European Association for the Study of the Liver Terms and Conditions