Multi-omics data integration reveals novel drug targets in hepatocellular carcinoma.

Dimitrakopoulos, Christos; Hindupur, Sravanth Kumar; Colombi, Marco; Liko, Dritan; Ng, Charlotte K Y; Piscuoglio, Salvatore; Behr, Jonas; Moore, Ariane L; Singer, Jochen; Ruscheweyh, Hans-Joachim; Matter, Matthias S; Mossmann, Dirk; Terracciano, Luigi M; Hall, Michael N; Beerenwinkel, Niko (2021). Multi-omics data integration reveals novel drug targets in hepatocellular carcinoma. BMC Genomics, 22(1), p. 592. BioMed Central 10.1186/s12864-021-07876-9

Preview

Text 12864_2021_Article_7876.pdf - Published Version Available under License Creative Commons: Attribution (CC-BY). Download (981kB) | Preview

BACKGROUND

Genetic aberrations in hepatocellular carcinoma (HCC) are well known, but the functional consequences of such aberrations remain poorly understood.

RESULTS

Here, we explored the effect of defined genetic changes on the transcriptome, proteome and phosphoproteome in twelve tumors from an mTOR-driven hepatocellular carcinoma mouse model. Using Network-based Integration of multi-omiCS data (NetICS), we detected 74 'mediators' that relay via molecular interactions the effects of genetic and miRNA expression changes. The detected mediators account for the effects of oncogenic mTOR signaling on the transcriptome, proteome and phosphoproteome. We confirmed the dysregulation of the mediators YAP1, GRB2, SIRT1, HDAC4 and LIS1 in human HCC.

CONCLUSIONS

This study suggests that targeting pathways such as YAP1 or GRB2 signaling and pathways regulating global histone acetylation could be beneficial in treating HCC with hyperactive mTOR signaling.

Interest & Impact

Downloads

37 since deposited on 24 Jan 2022
24 in the past 12 months

Citations

5 Citations in Web of Science ®
6 Citations in Scopus

Search

in Google Scholar™

Services

Actions (login required)

Edit item

Actions (login required)

Edit item