Figure - PMC

Skip to main content

An official website of the United States government

Here's how you know

Here's how you know

Official websites use .gov
A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS
A lock ( ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

View full-text article in PMC

. 2021 Nov 20;16(5):1091–1118. doi: 10.1002/1878-0261.13135

Search in PMC
Search in PubMed
View in NLM Catalog
Add to search

© 2021 The Authors. Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.

This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

PMC Copyright notice

Fig. 4 — Metabolic signatures and identification of the novel effectors Gal‐1, Gal‐3, and ZIP4 in PIK3CA‐dependent hepatocarcinogenesis. (A) Overview of samples and comparison groups for cDNA microarray analysis. Preneoplastic lesions were compared to age‐matched controls injected with the EV. EV‐injected 3‐month time points were contrasted to EV‐injected 6 months to rule out age‐dependent effects. Only one tumor at 12 months was available from the H1047R injection arm. The asterisk indicates a PIK3CA H1047R‐induced confluent preneoplastic lesion analyzed at 6 months. (B) Venn diagram of cDNA microarrays exhibiting overlap of regulated genes in the prespecified comparison groups. Selection criteria were Log_1.5 change and P < 0.01 for H1047R 3 months, E545K 3 months and control 6 versus 3 months, Log₂ fold change and adj P < 0.05 for E545K 5 months. The numbers of overlapping and uniquely altered genes are given. The three genes conjointly called in the PIK3CA injection groups are mentioned, while Lgals1 encoding for Gal‐1 is written in bold. (C) Heatmap of differentially expressed genes with selection criteria |log₂FC| > 1, adj. P < 0.05 and counts > 3 as determined in the E545K 5 months of comparison group. Specified genes are comprised in the GSEA hallmark gene sets PI3K‐AKT‐MTOR signaling (left panel) and fatty acid metabolism (right panel). Gradient scale color codes for Log₂ fold change. A cluster dendrogram is shown on the left and above. (D) GSEA was performed to identify significantly upregulated (red) or downregulated (green) biological processes in PIK3CA E545K 3 months, H1047R 3 months, and E545K 5 months of injection groups. Particularly relevant processes implicated with hepatocarcinogenesis are reported in bold. (E) Target genes glypican‐3 (Gpc3), Lgals‐3 (Gal‐3), and ZIP4 fulfilled the selection criteria prementioned above in (B) and (C). LGALS1 (Gal‐1) met the selection criteria described in (B). Gpc3 serves as an internal positive control as upregulation is expected in HCC. Target genes were manually chosen based on novelty, potential pharmacological targetability (Gal‐1 and Gal‐3), and early upregulation in preneoplastic lesions (Gal‐1). Presentation as a heatmap with identical color‐coding as in Panel (C).