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Molecular characterization of hepatocellular carcinoma in patients with non-alcoholic steatohepatitis

GSE164760 Homo sapiens (human) Expression microarray 170 samples Submitted 2021/06/29 Platform GPL13667
At a glance

Expression microarray · human · 170 samples

What it is
Expression microarrayGene activity read on a chip (the older technology that RNA-seq replaced).
Organism
Homo sapiens (human)
Topic
Hepatocellular carcinomaThis series is part of our curated briefing on it.
Samples
170 samples
Data you can get
A processed expression table (series matrix) and the array files, from NCBI.
Summary (written by the submitters)
Non-alcoholic steatohepatitis (NASH)-related hepatocellular carcinoma (HCC) is increasing globally, but its molecular features are not well defined. We aimed to identify unique molecular traits characterizing NASH-HCC compared to other HCC aetiologies. We collected 80 NASH-HCC and 125 NASH samples from 5 institutions. Expression array (n=53 NASH-HCC; n=74 NASH) and whole exome sequencing (n=50 NASH-HCC) data were compared to HCCs of other aetiologies (n=184).
Read the full summary ↓
Three NASH-HCC mouse models were analysed with RNAseq/expression-array (n=20). ACVR2A was silenced in HCC cells and proliferation assessed by MTT and colony formation assays. Mutational profiling of NASH-HCC tumours revealed TERT-promoter (56%), CTNNB1 (28%), TP53 (18%) and ACVR2A (10%) as the most-frequently mutated genes. ACVR2A mutation rates were higher in NASH-HCC than in other HCC aetiologies (10% versus 3%, p<0.05). In vitro, ACVR2A silencing prompted a significant increase in cell proliferation in HCC cells. We identified a novel mutational signature (MutSig-NASH-HCC) significantly associated with NASH-HCC (16% vs 2% in viral/alcohol-HCC, p=0.03). Tumour mutational burden (TMB) was higher in non-cirrhotic than in cirrhotic NASH-HCCs (1.45 versus 0.94 mutations/Mb; p<0.0017). Compared to other aetiologies of HCC, NASH-HCCs were enriched in bile and fatty acid signalling, oxidative stress and inflammation, and presented a higher fraction of Wnt/TGF-β proliferation subclass tumours (42% versus 26%, p=0.01) and a lower prevalence of the CTNNB1 subclass. Compared to other aetiologies, NASH-HCC showed a significantly higher prevalence of immunosuppressive cancer field. In three murine models of NASH-HCC key features of human NASH-HCC were preserved. NASH-HCCs display unique molecular features including higher rates of ACVR2A mutations and the presence of a newly identified mutational signature.
This dataset
Download · which file do I need?

Direct links to NCBI, no account and no request form. Pick by what you want to do: take the small processed table to look, the supplementary files to re-analyse, or the original raw data to start over.

1 · Just have a look

Processed table

The series matrix: one table of values per sample as the submitters processed it. The smallest download, and it opens in Excel or R. Start here to see what the data look like.

2 · Re-analyse it

Supplementary files

The count tables and other files the authors uploaded. Take only the samples you need.

All supplementary files ↗
3 · The original raw files

Whole study · RAW.tar

Everything the authors deposited as one archive (GSE164760_RAW.tar), including the raw array or instrument files. Can be large; the picker in step 2 takes just the samples you need.

What the files usually look like: For arrays the series matrix is normally the normalised expression table you want; the raw array files (CEL and similar) are in the RAW.tar.

Also filed as BioProject PRJNA691910. Searching any of these in the dataset finder brings you back here.

Samples in this study

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