Fig. 7: Using the transcriptomic FLC signature to evaluate in vivo models of FLC. | Nature Communications

Fig. 7: Using the transcriptomic FLC signature to evaluate in vivo models of FLC.

From: Liver cancer multiomics reveals diverse protein kinase A disruptions convergently produce fibrolamellar hepatocellular carcinoma

Fig. 7

UMAP plots of the PDX and the normal and tumor patient samples (N = 25) presented by Lalazar et al.30, using (A) all the genes and (B) using only the genes of the transcriptomic FLC signature. Each color represents a different patient, and the shape indicates if the sample is normal (circle), patient tumor (square), or tumor PDX (rhombus) tissue sample. The letter inside the square indicates if the sample is a primary (P), recurrence (R), or metastatic (M) tumor. The number inside the rhombus indicates the PDX passage number. C Comparison of the log2(fold change) in FLC PDX relative to normal samples from patients (y-axis) and the log2(fold change) in patient tumors relative to normal samples (x-axis), using only the differentially expressed genes (FDR < 0.05) in the FLC signature, obtaining a high correlation (R2 = 0.95). D Revisiting the stemness of FLC. Violin plots (in yellow) of the log2 normalized gene counts of AHR and the stem/progenitor markers screened by Oikawa et al.54 We analyzed RNA-seq data of 143 FLC patient tumor and normal tissue samples from different FLC studies15,26,31,32,33,34,35 (in variations of green) and the tumor line and the biliary tree stem cells studied by Oikawa (magenta). The color of the significance bar represents the variation of each of the groups in the X-axis compared to patient normal samples (red: overexpressed, blue: underexpressed), and the symbols on top represent if that variation was significant (*: 0.01 < FDR ≤ 0.05, **: 0.001 < FDR ≤ 0.01, ***: 0.0001 < FDR ≤ 0.001, ****: FDR ≤ 0.0001) or not (n.s.) in the Wald two-sided test performed by DESeq2. The box plots (vertical rectangles in gray) span the Q1, Q2 (median, black line), and Q3 quartiles, with the whiskers extending to 1.5 in the interquartile range. We used all the FLC RNA-seq data available: Requena et al. (this study), and the samples deposited in public databases from the studies of Francisco et al.33, Xu et al.31, Robinson et al.34, Sorenson et al.32, Simon et al.15, Hirsch et al.26 and the TCGA-LIHC study. We included the tumor model data of Oikawa et al.54. Their accession numbers are provided in the Data Availability section. Access can be requested directly to dbGAP, GEO and EGA under their privacy and confidentiality terms.

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